2023-07-02 - Interview Dr. David Sinclair - The Longevity Experts - The Harvard Scientist's Anti-Aging Protocol

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• Length: 2:01:10
• Interviewee: Dr. David Sinclair

Transcript

0:02	foreign [Music]
0:15	and actually I I was right it was uh it was brutal but uh but I do feel really
0:21	good now I actually uh they say it's it's good for your mind as well and I can see why I'm now just grateful to be
0:27	alive yeah uh so what that's like is if if listeners don't know is you uh you
0:34	start out in a really hot sauna and I'm not just saying it's like this temperature of the
0:40	surface of the Sun yeah so I normally do 160 degrees at my own gym this thing was cranked up Beyond 250 it was not that
0:47	high I knew he had I knew he said it around 200 I didn't realize it was that hot wow yeah uh it's at the point where
0:53	I was getting pretty dizzy um so you do that uh and then you jump into the you have a shower you jump in
1:00	the pool and you grab uh well first of all you swim underwater until you're basically out of breath and you want to
1:06	pass out then they give you weights and then you go you go into the deep end you're underwater below the top of your
1:13	head by by you know maybe half a foot uh and then you have to jump up and down
1:18	and you think okay I can do that uh there are two problems one is uh if you
1:23	don't make it uh you're gonna take in a mouthful of water which is what I did of course the first thing uh and then but
1:30	then the other problem is you go into this panic mode I I don't know if anyone's ever experienced was like to
1:35	drown but now I know what it's like to drown it is not pleasant you you can always let go of the weight and surface
1:42	there is that but but there's only one thing but there's standing there that's right a judgment of Laird yeah I would
1:48	rather drown than be embarrassed and give up uh so you know I looked like a stupid fish uh well a land animal in
1:55	water for a while I actually found out that I probably shouldn't have gone so far into the deep end uh that was my
2:02	first mistake uh but then what what do we do we also uh warmed up again in the sauna and then we jumped into to a big
2:10	bathtub with ice with about a couple of inches of ice on the top and that wasn't
2:15	so bad you know I've talked about cryotherapy before and saunas and uh
2:20	hypoxia but uh I've never done it so extreme you know I know when off is is
2:25	the guide of beat but I I usually go to my gym which is just four degrees Celsius I don't know what that is in in
2:31	Fahrenheit but it's not that cold as well your fridge temperature and I I found that brutal but actually going
2:37	into that ice water I was I was fine I mean the initial shock right you
2:42	I can't breathe I'm gonna yeah and then but maybe 15 seconds later uh with Gabby
2:48	uh Rhys telling me breathe slowly breathe slowly feel the heat rather than the cold you can convince yourself that
2:55	you're warm in this freezing cold temperature uh it actually was great and I I got to three minutes actually I was
3:01	going to do two minutes because she thought I was a bit of a wimp um got to three minutes and thought I
3:06	could just keep going this isn't so bad and they were pouring ice on my head at that point were you up to your neck oh
3:12	yeah I actually went under a couple of times yeah that's great and then you get out and you feel
3:18	great you feel refreshed grateful uh to be alive and uh yeah I would do it again
3:25	in a second how many uh how many people were there this morning uh there were about uh 10 of us yeah
3:33	I've got uh I have friends that go to that workout and I've had it I've had a kind of a you know sort of an open
3:40	invite to drop by I mean I kind of do my own I have my own workout and it's a bit of a drive for me so I haven't made it
3:46	over there but also in frankness like I'm I'm scared too like you know what I
3:51	mean like but what I've what I've heard was daryn a lean there this morning he's sort of a layered look alike like yeah
3:58	Darren been on the podcast very good friend of mine um Darren uh has said that the people
4:04	who fare well or the best are generally the people that that go into it with a
4:10	healthy dose of humility it's the problems arise when you get these super Alpha guys who think they're you know
4:16	basically Invincible like whether they're MMA fighters or Navy SEALS or whatever and think that they can do
4:22	anything and kind of attack it from a perspective of you know some kind of Dick measuring contest of like I'm gonna
4:27	do this better than Laird or whatever and they're the ones who get crushed and humiliated yeah there's a fair bit of
4:33	that today yeah uh yeah so Darren and I talked about uh he's interesting guy right he's super awesome yeah you guys
4:40	they talk forever we will we will meet up again good uh and uh yeah though uh
4:46	Justin Wren was there oh cool you know my friend Justin Wren that was his first time doing it too yeah and he was my
4:52	buddy MMA fighter exactly so Justin um was a fight for the Forgotten that's
4:57	his charity wonderful wonderful guy check him out he was my buddy and first thing I asked him when I was teamed up
5:03	with him was do you know CPR and uh unfortunately he didn't need to rescue me yeah
5:08	that's cool um well you've did you do I have this right like you have some scientific
5:14	background in thermogenesis don't you did you do you know Ray cronice did you work with him on some of the studies
5:19	that that he did on that or yeah right that's what I thought yeah so Ray Ray and I interesting story he was a former
5:27	NASA scientist not even thinking about metabolism or rent or health at the time
5:32	he was overweight by his own admission and uh I met him at a Ted Med talk 2008
5:38	it was and uh after my talk about aging and Longevity uh we were there with
5:44	Quincy Jones of all people um and uh he said David I've never heard a talk that's convinced me you know to
5:52	change my life I'm gonna do what you do and I'm gonna be a disciple now I thought okay you know Ray we'll you know
5:58	I'll see you later but he did it and uh so now what is that you know over 10 years later he has changed his life he's
6:05	he's a guru for for health and particularly cold therapy and we've
6:11	published a couple of papers one is on the metabolic winter hypothesis the idea that you know these days we we always
6:17	look for uh comfort and one of the problems is we never experience temperature variation in our lives we
6:24	will bundle up at night and we'll put on a jacket to go outside and this is one of the reasons we think that we all have
6:30	a tendency to get metabolic defects as we get older right raise now kind of
6:35	pivoted more into the nutrition landscape he's got this new book out with Julianna hover yeah Health span I
6:41	think it's called right Health Plan book yeah I gave it to my wife for uh for the holidays yeah cool yeah it's really
6:48	great I really liked uh those guys uh both of them they make a good combination because Juliana is the the
6:55	cook and runs the brain yeah exactly it is it is a good mix they live like right up the street here how do they yeah
7:01	they've been on the podcast um cool well I think it's interesting that you you
7:07	did the Laird and Gabby workout this morning with this combination of like sauna and Ice baths so maybe a good you
7:15	know first thing to explore is the relationship of those types of therapies
7:20	on aging and longevity right well the bottom line is uh you've
7:26	got to get out of your comfort zone get your body out of its comfort zone hormonesis is what we call it right
7:32	and the problem with today's world is marketing branding our own just our own
7:39	primeval brain we just want to be relaxed we want to be fed we don't want to feel discomfort and that's leading to
7:46	a whole bunch of problems and if we're not always telling our body things that could be problematic our
7:52	bodies don't care they don't fight against disease they don't fight against aging so these treatments uh and these
7:58	crazy things that I did today are all about turning on the the genes that we
8:04	work on uh we could talk about those in a minute uh but this is the revolution that's happening and there's a whole
8:10	bunch of people your listeners uh for example are realizing that one of the biggest problems in our lives is that
8:16	we've just been you know handled with kid gloves and the food we eat is also
8:22	not stressed out and that combination just turns us into mush it's interesting when you say the food
8:28	that we eat is not stressed out so that's that's about kind of taking in
8:33	stressed foods to prompt this um hormesis type effect through our
8:40	nutrition or you know explain what you mean by that right well we we um we're
8:46	working on Resveratrol the research story is what I first was known for in in Science World and we discovered that
8:54	a whole bunch of different plant molecules one of them is Resveratrol from found in red wine but there are a lot of others there's
9:01	quercetin from onions for example and they all activate these longevity enzymes that we have in our bodies and
9:08	they're found in plants as well and we're trying to figure out why would it be that these so-called polyphenolic
9:15	compounds like Resveratrol and quercetin why would our bodies benefit or why
9:20	would a mouse benefit by eating these molecules and what we came up with was the concept of Xeno hormesis Xeno means
9:28	between species and hormesis is what doesn't kill you makes you stronger and
9:33	it's uh even though it's a mouthful what what it it explains so much is that when
9:38	our plants are stressed that we eat uh we've probably evolved to sense when the environment and our food supply is
9:45	running out or potentially running out so if you're picking olives off a dry
9:51	you know a hill or you're eating fruit that's just had a massive drought uh
9:57	you're gonna have molecules in that food that'll tell your body hey these plants may not be around for the next month and
10:05	that was our explanation and it it really does make a lot of sense and is fitting with a whole bunch of data we've
10:12	had over the last couple of centuries that's like different species communicating with each other through
10:17	some you know unheard language it is it is and actually what it means
10:23	is a couple of things one is uh donate foods that are grown under perfect
10:28	conditions that works well for the Growers because they get food much more quickly think of the lettuce that you
10:35	buy that's in the greenhouse that's never been stressed is just watery white and watery right Avoid White and watery
10:42	what you want is uh denser Colored food the color is
10:48	actually an indicator that you've got these polyphenolic beneficial molecules so I I like to buy foods that are
10:54	locally grown organic and typically grown in in conditions that are not
10:59	perfect so what is it about it being locally grown or being organic
11:04	that enhances the hormesis impact or the stress response in the plants like we
11:10	couldn't you could you figure out a a conventional way of growing food where at the last minute you stress them
11:16	before you pick them or something like that so you're getting an enhancement of those polyphenols or whatever it is that
11:21	you're looking for that's exactly right that's what I think we should be doing um and there's a business idea uh okay
11:28	and in fact so uh Laird was telling me just uh an hour ago
11:34	that that I didn't know this that people who grow oranges and know what they're doing drive a nail into the tree I think
11:41	it was a day or so before they picked the fruit and that gives it these Extra Foods oh wow that's that's interesting
11:47	yeah so we've got to harm the plants just a little bit but it doesn't need to be all the time it can be just before
11:53	you pick them and think about grapes right what we do when we want to have great wine is we pick them just as
12:00	they're stressed that we they you try to pick them when there hasn't been rainfall for a little bit and then they
12:05	fill up with these great tasting molecules but also these xenochromatic molecules as well so how does that I
12:11	mean when when we're told like listen you should eat organic food it's really about trying to avoid the pesticides and
12:18	everything else that gets packed into conventionally grown foods but what is what is it about organic that relates to
12:23	this well you know there's organic and there's real organic I'm talking about the plants that you know may have had a
12:30	grub eat it or are exposed to too much sunlight that kind of thing being out in rougher conditions yeah
12:37	um hyper organic right right right not not suitable that's the name of the new company all right let's do it yeah
12:46	um that's cool well when you look at Laird I mean he's sort of a uh an experiment
12:52	in motion right like what is he 55 now yeah I think um doesn't look a day older than he did
12:57	you know 10 15 years ago and he's still killing it and I would say that he's
13:02	probably a pretty good example of of somebody who's practicing a lot of the things that you talk about I mean I
13:07	don't know what his you know supplement routine is with respect to you know some of the research
13:13	that you're doing but in terms of his daily exercise regimen and lifestyle habits uh it seems to be you know to
13:19	comport with the things that you talk about often yeah right he's the orange tree with the nail on it every day right
13:25	uh but I I totally believe it um and you but you you don't just do it with hot and cold and you don't just do it with
13:33	um what you eat there are other things you can do like when you eat you can also he's doing plenty of
13:40	exercise which is another thing and one of the the breakthroughs that we've had in the longevity field is that we used
13:46	to think you know let's go back 20 years ago that exercise was something that made your blood flow better and made you
13:52	healthier uh that eating less food was healthy because it lowered inflammation
13:57	somehow what we've realized is that all of these things are working through the same mechanisms and it goes back to work
14:04	that we did in my lab in yeast cells you know a little fungi that we grow that we use for bread and beer what we showed
14:11	and this has gone back to 2003 now is that there's one gene that controls longevity oh it's got a name called pnc1
14:18	it makes this molecule called NAD which is very healthy turns on defenses we
14:23	found that these yeast cells live longer when you gave them a bit of stress so if you turn up the incubator to 37 degrees
14:30	celsius instead of 30 they live longer or you starve them a little bit of or take away a little bit of the amino
14:35	acids in their food or what else could we do we could restrict the amount of sugar that they were eating that all
14:41	made them live longer but it all worked through this one genetic pathway and that was a breakthrough at the time
14:46	because you know even today most people don't realize that all of these things that we do are converging on this master
14:53	regular regulatory pathway for our health is that part and parcel of this
14:58	you know kind of singular information Theory of Aging that is you know the sort of the foundation of your work yeah
15:06	it all connects it's all slowly coming together it's taken 30 years of work but
15:11	we're getting there I can see the end of the tunnel and what what is interesting is that so this NAD molecule is the fuel
15:19	for a class of enzymes that acts like the traffic cops in the cell they they
15:24	send out the troops to repair and fix things and one of the main things they
15:29	do we found is they control the expression or control information in
15:35	the cell not not the genetic information but how the genetic information is controlled and these genes are called
15:43	sirtuins so sirtuins you can think of as The Pianist that plays the genetic piano
15:48	and when they're not active the pns becomes complacent makes a lot of mistakes and
15:55	ends up becoming event demented and that is what I believe is a large driver of the aging process but if you're always
16:02	activating your sirtuins The Pianist keeps playing the concerto for much
16:07	longer and you we stay younger right we talked about this uh last time the analogy we used wasn't The Pianist I
16:13	know that's like the the title of I think the second chapter in the book pianist where you explain all of this
16:20	the the metaphor that we used was was you know highway traffic right and and
16:27	getting dispatched you know away from their their true role to kind of deal
16:34	with crises potholes in the roadway and whatnot and then the signaling you know getting screwed up and then basically
16:41	all of the kind of traffic copying going haywire and these these you know the NAD isn't going where it's supposed to go be
16:47	going and the sirtuins aren't where they're supposed to be and the whole kind of system breaks down that's right and we first discovered this I was at
16:54	MIT as a postdoc originally moved to Harvard in 1999.
16:59	those years were were formative what we discovered in yeast cells it's incredible right you can learn from a
17:04	little fungus these big Concepts the sirtuins and the yeast cells were
17:09	maintaining the identity of those yeast cells and making them stay young and healthy for longer by keeping the gene
17:17	piano working for longer now what we also realized was that you can distract
17:23	them from their main job The Pianist can get distracted you know imagine you know you you start trying to you know whistle
17:30	or get get in the face of your pianist it's essentially the same and what is a major distraction for these sirtuins in
17:38	their normal job is broken chromosomes broken DNA DNA damage and we know that DNA damage can accelerate aging anyone
17:45	who's lived in California or Australia like we have knows that DNA damage from
17:50	The Sun Will accelerate aging but no one has ever fully understood why and it's
17:56	been a mystery and mutations don't seem to be the main driver this is the old Theory so what I think is going on is
18:02	that these uh breaks in the chromosome it's DNA damage is distracting these
18:08	certains from maintaining the symphony perfectly they get distracted they go off and do stuff fix the chromosome and
18:15	then most of them come back and keep playing the piano but some of them never make it back to where they should and
18:22	over time that's cumulative and you end up with a cacophony so the goal the job
18:27	the mission is to maximize the efficiency to really optimize the
18:33	sirtuin functionality right and the way to do that is to make the body think
18:39	that it's it could run out of food or has to run away from a saber-toothed tiger and that all relates back to the
18:47	activity of these sorts because then they're not distracted by these sort of frivolous situations and they're they're
18:53	focused on the the most important job that they're kind of created to deal with yes and the other way to think
19:01	of it is without enough fuel and NAD is their fuel this little molecule called
19:06	NAD if you don't have enough NAD they are very slow at doing their job they kind of they get detached from what
19:13	they should be doing and then they've they've drift off through the liquid in the cell and they don't have enough
19:19	energy to to fully fix the DNA quickly and they don't have enough energy we think to come back to where they came
19:25	from but if you do have all the energy in there in their Prime still the youthful
19:30	sirtuins they can fly off and come back but it's without the fuel the NAD or you know
19:37	Resveratrol is also an activator that's one of the things we figured out in the 2000s so the combination of the fuel and the
19:44	activator Resveratrol and the NAD is a fantastic combination we think for maintaining that that
19:51	epigenetic Symphony as we call it right so what is the state of the union when it comes to to the scientific research
19:59	on Sonic therapy you know cold therapy and its impact on NAD and sirtuins and
20:07	and thus aging or anti-aging uh that's a really good question you just got a big smile yeah I I can I can see why you're
20:15	so good at what you do I'm just trying to follow my curiosity here I'm trying to keep up and and I really want to like
20:22	understand this so anyway go ahead uh well uh so the connection is that uh
20:30	the sirtuins are actually um waiting for more NAD production and
20:36	remember that old yeast cell story that I told you about there was one gene that was turned on by temperature and by low
20:42	amino acids that Gene makes NAD okay in our bodies we have the same
20:48	equivalent Gene it it's uh it's called an MPT nampt and we discovered is now
20:55	2007 that when you stress human cells in the dish and in in in the body as well
21:01	uh that you turn it on so an amputee comes on and it makes more NAD for the
21:07	body and these are twins can do a better job so an ampute is really interesting we most people don't know about it or talk
21:14	about it so I'm glad you brought it up that's why I'm saying yeah we definitely didn't talk about this last time right so now I haven't talked about it
21:20	publicly nempt is is the master regulator of NAD production it's the what we call rate limiting step in
21:26	making an ad from precursors like vitamin B3 and so we took human cells we put them
21:32	in the dish and we stressed them out so we gave them not enough sugar we gave them too much temperature we what we
21:38	call heat shock them and on came this an amputee and they made more NAD so what I
21:43	think could be going on is that the stress on the body when I'm you know 200 and whatever Fahrenheit and then jump
21:50	plunging into uh basically zero degree celsius that is making my body make more
21:56	NAD essentially mimicking the effects of exercise and hunger just a different way
22:02	and making Meister twins work optimally and that is something that uh I think is
22:11	underappreciated that this one gene is the probably the main cause of the
22:18	benefits of all of the things that we have figured out over the last two thousand years of being healthy and is
22:23	there an understanding of the relationship between the hot and cold is it that combination that makes it effective could you just do this on or
22:30	just do the cold therapy or like how does it you know has that been explored not well yeah no no and I'm asked all
22:36	the time what's the best combo of diet right exercise we'll figure that out and
22:43	then you know you the Keys of the Kingdom arrive yeah but you have Rhonda Patrick talking about sauna and then you
22:49	have the Iceman Wim Hof talking about the cold therapy and now you have people like Laird who are combining these two
22:55	and I'm just trying to get a sense of like what is the ultimate stress or you know hormesis inducing
23:02	protocol that's going to activate this NAD producing signaling mechanism right
23:09	so we need to figure that out but I have a philosophy that drives what I do and what I talk about and that is that you
23:15	don't want to do the same thing over and over again mix it up right because you you acclimate to that right and it's no
23:21	longer it's no longer creating the stress response exactly so I don't exercise every day not that I could but
23:27	I don't it's a convenient excuse yeah really true you gotta pulse it right
23:34	because as soon as the body gets used to what you know I'm in this ice bath and after three minutes I'm like what's the big deal right you gotta you know switch
23:40	it up and that's why I think that the best thing that we know right now is that you
23:46	want to do uh some some exercise then you want to do the sauna then you do the
23:51	ice bath that's what I do and until I know more I'm going to keep doing that right similarly I would imagine you know
23:59	when you look at Walter Longo and his fasting mimicking diet and all the science that's emerging around intermittent fasting I mean the the
24:06	benefits of that are kind of boiled down to [ __ ] mises right you're trying to create a stress response that activates
24:12	certain you know Pathways in your in in your system that that relate to aging or
24:18	anti-aging but I would imagine that you could you could develop a set point with that as well kind of acclimate to that
24:24	and get used to it and then you're no longer experiencing that benefit do we is that is that is does it work that
24:30	same way with the eating well it's it's complicated because there
24:36	there are two experiments that have been done uh one is to consistently just give mice low-grade food and basically mix
24:43	their food with cardboard cellulose and that works so if mice are nibbling all day on low calorie food that still works
24:49	so you don't have to do intermittent fasting for this to work you never get used to not eating yeah yeah your body
24:56	will still respond um but at least we understand what's going on and again it's this nempt Gene
25:02	in large part that's turned on when your body doesn't have enough glucose and
25:08	insulin is being produced but also this intermittent fasting the reason I like it and I you know Vault
25:14	has been an old friend we used to by the way we used to study yeast cells together yeah where we both came from
25:19	um the intermittent fasting for me is is better because it means you can eat instead of
25:25	seventy percent normal calories you can eat 95 percent or 100 calories you just
25:30	have to squeeze it into a window of a few hours to be optimal and that's just easier to do right and in the mouse
25:36	world if we do calorie restriction which is this low quality diet a low calorie diet of course versus intermittent
25:42	fasting uh they both work about the same that you know you can argue about minutia but
25:49	basically they all extend lifespan but the mice are on intermittent fasting can eat a lot more in their lifetime yeah
25:55	and you know if you're not eating food and enjoying life you know it's not right
26:01	but I need to get hormesis hormesis I'm going to starve myself
26:07	well yeah I'm I'm skipping one to two meals a day and and it's changed my life I feel great and a lot of people say
26:14	like it it makes me feel queasy or my stomach's burning I found I get used to it and if you if you find that it's too
26:20	hard try a cup of hot water I think coffee is is great tea and that gets me
26:26	through the morning yeah I've been playing around with it and experimenting with it for a while and and I found that
26:33	that you know it's so much of this is psychological and mental like I'm now in a place where you
26:40	know there's plenty of days where I won't eat until dinner and it's not because I'm trying to provoke suffering
26:46	like it's just I'm not even really thinking about it where you really realize realize it
26:52	and I know you posted about this on Instagram the other day is when you fly when you get when you get on a long
26:58	plane and I use those generally as opportunities to to play around with this thing because I'm not going to eat
27:03	the food that they're serving on an airplane and it's hard to get healthy food in airports and the like but for
27:09	the most part most flights are you know four to six hours unless you're going to Australia which we're going to talk about
27:15	um it's not that big of a deal right and then when the when the flight attendant kind of repeatedly drops by and says are
27:21	you sure you don't want anything and the look on their face they're just like amazed that you're not eating and you're
27:26	like it's not that big of a deal right that this like but but you've paid for this it's free you have to eat it do you
27:32	want some ice cream and cookies no go away I know the more you say no the more
27:37	they come back I know yeah yeah but I I agree with you it's a moment to really test yourself
27:43	because you're sitting there and all you've got to think about is the food and the person next to you is eating
27:49	right and then then you really test your mental will not actually I use that as a way to test myself and one of the things
27:55	I do is I think you know it's fine to eat now but what do I want to look like feel like a day a
28:02	week from now 30 years from now and that allows me to help my future self yeah
28:08	well you don't look a day older than the last time we spoke which was at least a year ago I think yeah so 50 51 50. uh no
28:17	I'm still I'm still 50 but uh yeah no gray hair I'll let you know no yeah definitely not a gray hair on your head
28:24	yet um and what maybe this is a good place to talk a little bit about the
28:29	difference between um the biological clock and what you call
28:37	Horvath clock right the hor the Horvath measure of Aging yeah can we talk about
28:42	that yeah that's really important uh it's a massive breakthrough in the field of Aging for many many reasons one of
28:48	the big things that's held us back in studying aging is we didn't have a a real measure of what
28:54	aging was you could look at a mouse or a human and say okay they look young or they look old big deal but we needed a
29:01	mathematical and a a non-subjective measure and we finally
29:07	have that finally uh until recently all we had was some blood tests that tell
29:12	you you're looking okay you're looking healthy you're on the right track but the clock changes everything because
29:18	it's a mathematical clock and actually Horvath is Steve Hove that's one of my very good friends great
29:24	guy uh he's a mathematician by training and somebody got their clock measured by him well I'll tell you in a minute about
29:30	how the clock works but uh someone said oh I got a really bad result on my clock I'm biologically 10 years older are you
29:37	sure the clock is ripe and he said as in true German form he's a I think Austrian
29:43	actually he said there's a greater chance that the Earth will be hit by a meteorite tomorrow
29:49	that's how good this car is and it's it's not so hot on the bedside manner though no no but he's got a great dry
29:55	sense of humor so what we've got actually is and the beautiful thing about it is it's not just helpful to be
30:01	able to say this is how old an animal or a human is biologically but also it comes back to this information Theory of
30:08	Aging the epigenetic information is what I think is lost during aging that's the most important thing the basically The
30:15	Pianist not the piano right the clock is measuring the pianists um state of mind right and when so what
30:23	Steve's doing with his clock is measuring how demented The Pianist is so that that's of course a metaphor what's
30:29	actually happening in real life is that our DNA uh has chemicals on it that tell
30:35	which Gene to be on and off that's basically the the notes are uh for for a
30:40	symphony the the right score but it when you're born you have a certain
30:46	pattern of these what are called methyls These are little chemicals just carbon and three hydrogens that bond to the C
30:53	letter you know on DNA there's a ctg right so the C's get this methylation it's called just a chemical that sticks
30:59	there and doesn't come off unless the body takes it off it's a permanent Mark and that's what says that Gene needs to
31:06	be switched off that Gene in your brain only comes on in the liver so keep that off for the rest of your life and I
31:13	think that that pattern the changes over time is what drives aging now what Steve found independently
31:19	uh for me is that if you can read the pattern of those methyls
31:24	it'll change over time and if you use machine learning and say okay this is the pattern of a 50 year old 20 year old
31:31	even a five-year-old you can draw a straight line and then once you've got that straight line he can hear I can
31:38	take your blood map your methylation pattern as we call it and place you exactly within a few
31:44	percent error of where you are on that curve or on that straight line and then we can say you're likely to die
31:50	in July 2050. oh wow I would imagine that gets more and more
31:55	accurate every day right as the data set grows it is we're learning a lot we've got now clocks for
32:01	uh human skin uh the blood in my lab we've got Mouse liver and kidney but
32:08	also here's the amazing thing we didn't know this until just a couple of years ago that you can take a dog's clock
32:16	and use it to predict the age of a human or a sheep or a bat what is you know
32:21	that that sounds fanciful but what that's telling me um and Steve is that there's a universal
32:29	underlying clock of Aging in mammals at least um and I think it probably goes all the way back to jellyfish we're going to do
32:35	a jellyfish clock because jellyfish can be immortal so we want to figure that out how that works but what we basically have
32:43	converged on we think is that I'm saying I think we understand what
32:49	drives aging mainly is the loss of that perfect pattern of which genes are on and off when we're young and that Steve
32:55	has a figured out has figured out a way to actually quantify that so what is your what is your age
33:01	according to the Horvath method I don't know yet and when are you gonna die what do you mean here you don't know no no
33:07	I've been too busy but um no I've I've done just the the old-fashioned blood tests and but I'm gonna do it uh I'm not
33:15	avoiding it I'll tell you what we are doing that I haven't told anybody it's a little bit of a secret but why not
33:20	uh right now the test costs a lot of money um I think a really good deep test would
33:27	cost them you know at least 300 sometimes thousand bucks to do so it's not cheap
33:32	and you can't do it every week you can't do it every month but we're working in my lab and we just had a breakthrough we
33:38	think we can bring it down to five or ten dollars wow and then you could do it at home right if you if you're brave
33:44	enough there's another business for you yeah well that that will be hopefully a business uh that's one of the reasons
33:50	we're doing it but also right now it's too expensive to measure the age of a million people but without technology we
33:57	could do that right and then things get interesting then we can say people who drink this coffee
34:02	that I'm holding my hand uh how do they do does their clock go backwards or not and finally we can figure out within a
34:10	short period of time what things work for slowing or reversing aging and there was a study that Steve was on uh
34:18	recently last year that at least suggested with a small number of people that a treatment in humans could
34:25	actually reverse the age of those people by at least a couple of years wow yeah then the data becomes unbelievably
34:31	valuable right it's it's less about what the consumer finds out about his or her life and more about the value of that
34:37	data set and what you can extrapolate from that a lot of people are scared to measure their age because I don't want
34:42	to know that you know even myself I will admit I'm kind of scared to look yeah what would happen if it said You know here here you are that the anti-aging
34:50	longevity guy you're gonna die in two years yeah that would be that would not be good for a bad day for business
34:56	yeah well you know I don't live perfectly that's for sure um I don't every day I jump up and down
35:03	in a swimming pool like I probably should be and I'm on planes a lot which is not good I'm sitting down a lot I'm
35:08	typing so there's I might actually be older than I look who knows I will I
35:13	will tell everybody when I get that data but here's the really important Point Rich which is that
35:19	data is important right I'm data driven as a scientist but everybody with their body should be
35:24	cognizant of how they're doing just ignoring aging is not going to make it go away or slow it down
35:31	so what happens if you find out that you're a bit older than you actually are
35:36	based on your birthday candles what does that mean is it do you just go to bed and get it have depression no this is
35:42	enabling what it means is that you can actually alter the trajectory of your life that trajectory that you're on
35:49	it's not fixed just because I say you're going to die beginning of 2050 that's if
35:55	you don't change anything but you can bend the needle and the things we're talking about today the hormesis effects
36:01	we already know can actually change the slope right since we last spoke has
36:07	there been any interesting breakthroughs or new studies or or science that has
36:12	kind of shifted or or expanded your perspective on any of the things we talked about last time
36:18	uh yeah lots uh you know every day I before I get out of bed I'm actually reading scientific papers can you
36:24	believe it uh pretty much every day I'm excited by something new there was something a couple of weeks ago that came up that that I'd been hoping to see
36:31	uh for at least 12 years and that was to find out uh why does Resveratrol
36:38	activate this to an enzyme why is that so one idea is that we're
36:45	sensing the stress and adversity of our food but we also have hypothesized since we
36:51	first discovered Resveratrol and its role in aging anti-aging is that it's probably mimicking something that our
36:58	bodies make uh we call it the endogenous activator The elusive endogenous activator
37:05	and uh what this paper showed was that uh the byproducts of the the what we
37:13	call lipolysis the breakdown of fat when you're when you're hungry produces monounsaturated fatty acids the kind
37:19	that you can get from olive oil right those molecules circulating in the blood are about a thousand times more potent
37:27	than Resveratrol and activating this longevity enzyme so what does that tell us first of all
37:33	Resveratrol is pretty cool you can mimic your body's fasting state by by ingesting it but also it means that uh
37:41	we've kind of been Vindicated because we got a lot of crap for Resveratrol yeah in the early years if you if you Google
37:47	your name in Resveratrol there's a there's a lot of [ __ ] talking coming in your direction uh yeah some earlier
37:53	stuff from years ago well yeah and it's been it's been a brutal uh part of my career uh but we've always gone back to
38:00	the bench and done better science because of those challenges and one of the big challenges in my career was that
38:06	Resveratrol we said it activates this enzyme by actually literally sticking to and
38:13	binding to it physically and making it more active like a Pac-Man would move faster and then a couple of companies
38:20	came out big big Pharma companies and their scientists said literally That is bull
38:26	right and that's brutal when that happens and everyone almost everybody except close friends said are we going
38:32	to believe the companies and David's wrong and that that's a tough time in anyone's career and my lab shrank down
38:38	to about a fifth of its size and couldn't get great money but we fought back uh we we went back to
38:45	the bench I got out of bed eventually and uh I had a student called basil Hubbard who's now a professor in Canada
38:52	he didn't give up everyone else in my lab was kind of like oh we're screwed let's get out of here sinking ship he
38:57	said know what you know what I'm going to test this and he he worked really hard and figured out that the the
39:04	experiment that we originally did to show that Resveratrol was activating the enzyme in the test tube was not an
39:10	artifact and it was actually real so we published that in the journal science in 2013 and so that the scientific hubbub
39:18	went down basically we were you know largely accepted that we were
39:25	correct but out in the media you know no one no one cares about correction of a
39:30	scientific idea it's all about the controversy that's interesting and so that's still out there in the world so
39:35	anyone listening who who knows that this was controversial we've actually scientifically resolved the controversy
39:40	of whether it's true or not it is true but it still left open the question is there something in the body that we make
39:47	that activates the enzyme like Resveratrol does so this new study then basically kind of
39:56	you know what I infer from that is that we should be eating monounsaturated
40:02	fats or that we should somehow be TR be trying to trigger this lipolysis you
40:07	know situation so that we are you know creating this impact that we're trying to have I mean what do we do with this
40:13	information yeah well I think the the lipolysis we're going to be doing with intermittent fasting anyway it's up and
40:19	down but I think that the most exciting thing um about the paper is that they found
40:25	that oleic acid from Olive Oil is also a very potent nanomolar for the
40:32	aficionados activator of sort one so what does that mean that means that when you eat olive oil
40:39	you're actually activating your sirtuins quite potently because it's also just like Resveratrol mimicking this
40:45	lipolysis effect and maybe the an eye and the authors of that paper have
40:51	written that this could explain why the Mediterranean diet is so healthy or
40:57	alternatively in in lieu of olive oil you can get the same result via Resveratrol well yeah so one thing that
41:04	occurred to me was so I've been taking Resveratrol for over 10 years now and I'm glad I have maybe I should have been
41:11	taking a little bit of olive oil as well but Resveratrol has no calories so I've basically been drinking olive oil for
41:18	the last decade without the calories right that's a good thing um what is we talked a little bit about
41:24	this last time but I think it's worth exploring a little bit more um what is the difference between
41:31	taking in Resveratrol via you know red wine versus a supplement in terms of
41:37	bioavailability in your body's ability to kind of metabolize it yeah so Resveratrol is unfortunately a
41:44	pretty insoluble molecule now in the plant what they the plants do is they
41:49	put a sugar on on it and it's quite soluble for the plant but for some
41:55	reason we uh we like to purify it away from the sugars uh well not for some reason because if you don't it's it's a
42:01	sticky horrible mess so we we isolate Resveratrol that's free and clear of all these other bells and whistles that the
42:06	plants like to stick on them but what we're left with is basically a crusty dry powder that doesn't get absorbed by
42:13	the body very very much and even if it does it gets basically gotten rid off by the liver
42:18	so what we had to learn early on uh even for worm studies when we were showing Resveratrol extensor worms is you have
42:24	to dissolve Resveratrol in some sort of solvent so for worms we use a thing called DMSO in humans we found uh in the
42:32	early 2000s that you if you mix it with a fatty meal um and that's true for mice as well you
42:38	get about five to tenfold the levels and so I always mix my Resveratrol with
42:44	something that's got a little bit of fat in it like a homemade yogurt every morning and what I what I've noticed is
42:50	that the studies in people that have not shown the benefits other
42:55	ones where they've just given a dry capsule to the patients or the subjects and those that work are those typically
43:00	that are given it with a meal or something that the Resveratrol would dissolve in right so there is some sense
43:05	that that that definitely increases the bioavailability and absorption no question we did these clinical trials a
43:11	long time ago as we were working our way to making a drug um but we actually we ended up making
43:17	synthetic molecules that were a thousand times more effective than Resveratrol we didn't know at the time we were making
43:22	the equivalent of olive oil electric acid right but I guess now we do know that those molecules actually went into
43:29	clinical studies with with humans that's also not very well known and there's a the skin condition psoriasis
43:35	um it worked really well they popped a pill of these activators and one of these activators and the patients did
43:41	better now I'm still hoping by the time I die I'll have one of these medicines on the market we're not there yet yeah
43:48	um and that's actually one of the brutal take-home messages actually is um I don't want to complain because I've been very lucky in my life it's it saddens me
43:55	that that in science you can be derailed by a decade for a decade by you know by
44:02	your your naysayers and I'm hoping to get things back on the rail seems like so far so good well the last time we
44:09	spoke you know this book had not come out yet now it's been out you've been doing the you did the book tour thing
44:16	um and you know a kind of canvassed some of the press around that and it's interesting
44:22	because it's my sense is that on the one hand kind of in popular culture you're
44:29	being feted and and celebrated for this book and your work
44:34	um breakthroughs you know this bold you know taking this very bold position that that aging is reversible that we're on
44:41	the precipice of of new science and breakthroughs that are going to revolutionize how humans live their lives and think about their lives uh and
44:49	on the other hand you know some pushback from the conventional scientific community and some grumbling amongst you
44:56	know the old guard saying not so fast uh you know exactly you know what I mean
45:01	they like Fast yeah you're you've got your your foot on the accelerator and and they seem to be saying you know slow
45:08	down your your kind of out over your skis here yeah that's true but that's um you know
45:15	so be it we we have a certain amount of time on this planet um and I'm I'm going as fast as I can
45:21	the other thing that most scientists don't don't realize is sometimes it takes us a decade to publish our work so
45:27	we we know I know a lot more about what we're working on than other people and when they say to me oh David or say
45:33	behind my back David's out over his skis they they only think that I know what's published but we've got all this other
45:39	stuff so when we were challenged by these companies um even though it was sad I had a whole
45:47	body of data from my lab that said uh I'm not don't be so sure of yourself but
45:52	yeah it's tough as a scientist uh especially one at a conservative University like Harvard uh you know I
45:58	often get my Knuckles wrapped because I'm out there right but but I do it not because I'm seeking fame or anything I'm
46:05	a pretty shy guy but I I do want to see Technologies adopted within our lifetime
46:11	you know it's fine future Generations will do well but I really do think that
46:17	it would be a real shame if our generation was the last to live a normal lifespan
46:22	you would think that Harvard would celebrate this I mean don't they want people that are sort of breaking
46:29	paradigms and pushing the envelope and what is the purpose of a lab if not to test the limits of our of our
46:35	understanding and to kind of you know dream boldly yeah well so in Harvard's
46:40	defense what what gets them riled um up is when I get misinterpreted by mainstream media
46:48	uh so I rarely uh now talk to that never happens yeah it's tough as a scientist
46:53	because you you say here are the facts here are the facts and the headlines out for me typically is Harvard scientist
46:59	says we're all going to live to 150 right which I'd never have said but then the university says David what the heck
47:04	are you saying it's like so you know it's easier for me to not now talk to uh sensationalist
47:11	media and I've now a much more comfortable doing this kind of thing where I can talk directly to the public
47:17	right and I appreciate it not getting misquoted yeah um and uh and and how's the lab doing
47:23	like how and how are the colleagues like in the wake of the book Success New York Times bestseller like you know it's
47:28	books everywhere everywhere you look I see it um you know how are they kind of uh you
47:34	know um acting towards you now uh good yeah I've had no backlash about
47:40	the book which surprised me because of it's a bold thing to say yeah we figured this out it upsets a lot of people right
47:46	but um as far as I know they're not upset in fact I've had a lot
47:51	of uh praise from colleagues at school the book is
47:56	um I mean congratulations I think it's a it's I really think that it is um a paradigm breaking Master work and
48:03	what's what's really interesting and unique about it and and I suspect unsus uh you know sort of unexpected for
48:09	somebody who's gonna pick this up is that is that it's not just this hardcore
48:15	scientific Tome it's sort of you weave in a little Memoir aspect to it you tell
48:20	these stories there are incredible illustrations throughout I know you won like an award for the illustrations or
48:26	the artist did um and you tell these Amazing Stories and you have these kind of poetic you
48:31	know chapter titles so it's a different experience than than I was expecting looking into it like it's it's it's kind
48:39	of General genre bending in that regard well thanks uh I appreciate it you know
48:44	anyone who knows me I'm not not really a scientist I'm doing science because I have a goal in life like in high school
48:51	I was an artist and the the some of the illustrations at the back of the book I drew myself the headshots so I'm an
48:56	artist masquerading as a scientist um but I think they go well together actually I'm I think in terms of shapes
49:02	and things moving around I'm not um so much a mathematician mathematician but that that's why the book ended up being
49:09	like that I also have to give a big shout out to my co-author Matt laplan who took a whole bunch of crazy ideas
49:14	that I had and synthesized them and wove them into this narrative including some history which I really believe that the
49:21	best way to predict the future is to look back over the last 200 years to see where we're going especially also when you look at society and there are a lot
49:27	of things are said about the work that we're doing oh we're all gonna run out of jobs we're going to have not enough
49:33	food what are we going to do with all these people of the population if you look back at history
49:39	we've always been worried about that right and there are solutions I mean it's not all perfect we can't have
49:44	unlimited number of people on the planet but that's why I wove history in there because you you forget that people have
49:50	gone through these kinds of things before and come out the other side much better I don't think you'd want to go back to the 1840s with cholera rampant
49:57	no but we have our own particular set of problems now and I I do want to explore the kind of ethical and philosophical
50:04	implications of your work and I think a good kind of inroad into that is to
50:09	start with Australia right you're Australian last time you were on the show you told these amazing stories
50:15	about your grandmother Vera wearing a bikini on Bondi Beach for the first time and just being this like you know I
50:20	don't know like I just wish I had someone like her in my life she just sounded amazing and I can see how you
50:26	know her influence on you has catalyzed this path that you've been on but I spent I just spent a month in Australia
50:32	I was there for all of December I think you were probably there for part of that as well right yeah I think we probably
50:38	overlapped yeah and uh and it was it was quite something being in in Sydney in
50:43	amidst these fires and it's I know it's even worse right now in terms of air quality around that City
50:49	but it was relatively dystopian on days people walking around with masks on you
50:55	really you know couldn't breathe the air the sky was orange the entire you know Coastline I mean
51:01	it's just the the the sheer scope of what's happening there right
51:06	now is hard to imagine I mean I saw a new story this morning that said the smoke from the fires has actually
51:13	circumnavigated the entire globe and is now back to Australia after going all
51:18	the way around the planet Yeah well yeah it it definitely feels like Armageddon when you're there and even I I live in
51:24	Boston of course and uh a few days ago it was 70 degrees and you know you walk out there and you go this is this is
51:31	craziness uh you know I grew up in Sydney right on the bush as I describe in the book I almost had my house burned
51:37	down actually last week my brother's family lost a house it was all burnt down and there's nothing left except a
51:43	bit of Steel on the ground everything else just toasted it it it really brings home the fact
51:49	that we are living in in dangerous times and you can deny it you can deny that
51:54	the world isn't changing and we've lived through these times before but let's just face it let's use Occam's razor the
51:59	simplest explanation is that the world is [ __ ] up and we are the cause of it it's not that hard to admit unless
52:05	you've got some other agenda uh and Australia is a if you've never been to the Australian bush you've got to
52:12	realize this isn't like a forest with soil this is tindered this is the kind of leaves that
52:18	if you put in a fire they explode they're full of oils eucalyptus oil mainly and it's not hard to start a fire
52:25	a bit of you know throw a cigarette out or whatever once it's going this is basically uh a fire that you cannot put
52:33	out because it's it's not just going from Leaf to Leaf it's going from tree to tree across the top it's creating its
52:40	own weather patterns there's a couple of firemen were killed um because the truck was caught in a
52:46	tornado and blown on top of them right that's Armageddon kind of stuff um and you go there and there's just
52:51	this I think the Australians are in Shock when I was a kid my house almost burnt down I know what it's like to feel
52:58	that your house has been burnt down the problem that I see now is that
53:04	you know this is this is not a one-off fires in Australia normally starting around February
53:09	and you know we're we're in December or January and this could be the new normal in California right now it's it's fires
53:16	all year round pretty much yeah and this fire in Australia has been going on for like four months at this point right
53:22	right right and say first singular but it's a lot of different fires hundreds
53:27	that are meeting up with each other Etc yeah yeah it's just it's a scary world and we have to do something and so what
53:35	so most people look at me and like oh David you you study mice what would you know about climate change
53:40	I have a conscience and I think about the impact of my research all the time and what I've written about is that we
53:47	need to mobilize resources on the planet billions if not trillions of dollars to to tackle this as well as other problems
53:54	we have like energy resources consumption you've got to take money from somewhere to solve these problems if they don't
54:00	solve themselves we can take it from the military you could there's opposition to that
54:06	you could take it from education you don't want you to do that what about health care right now we waste billions
54:13	of dollars taking care of the elderly who don't need to be old if if we're right and we do the kind of
54:19	things that we talk about today as well as advances we could have a world by the time we're elderly where people in their
54:26	80s are just starting a new career like my dad did yeah that's a world where you a globe that would save trillions of
54:32	dollars okay so now it's easy to say you save a trillion dollars but that's money that can be poured into solving these
54:38	problems I like to think about Old London a lot because old London in 1840 the cholera thing that I then mentioned
54:46	people in the 1840s they weren't solving the world's problems because they were too busy trying to figure out why everyone's dying
54:52	in a world where people are not dying and you're not taking care of them then you've got the resources to solve these
54:57	problems and I don't know any other way besides stopping the military spending of getting a few trillion dollars to
55:03	spend I mean the silver lining in what's happening in Australia is the
55:10	opportunity that it will catalyze political will right and one of the things that was interesting when I was
55:16	there is I didn't fully have have a sense of just how conservative the
55:21	government is and you know everything that's going on with the PM and he goes to Hawaii in the middle of all this on
55:28	vacation and you know the the impact of the coal industry on kind of you know
55:33	the political perspective on what to do or not to do is all very interesting right so you're somebody who is
55:39	incredibly optimistic about about human Ingenuity and you know
55:45	excited about the potential of our species to innovate our way out of any problem that we find ourselves in and
55:53	I can see that perspective and to some extent I can agree with that but I think the limiters are are really you know the
56:00	the the governments and and the politicians who are tied up in Old systems that are
56:06	holding us back and basically exacerbating the problems we're trying to solve yeah no doubt no doubt and uh
56:12	just to to hit the exclamation point old London when um they figured out that it
56:19	was actually cholera from the water well uh What uh snow did was he removed the
56:25	handle of the pump and cholera went away but talk about politicians what's not
56:31	really known is that the politicians were under pressure uh because people
56:36	didn't want to admit that the fecal oral route of infection was true they thought it was from the air so they actually the
56:43	politicians put the pump handle back on and for another couple of years there were still cholero plagues in London so
56:49	you know you talk about politicians screwing things up I absolutely agree that if we can mobilize human Ingenuity
56:54	we can solve anything but we do a very bad job of that I think where we are here in California is a hot spot for
57:00	Innovation but most of the world doesn't really innovate yeah when we look at the state of health
57:06	care in the United States I mean it's just it's it's horrific compared to where it could be
57:12	in terms of what we could be doing for people and it's such a Byzantine mess I don't see our way through it or out of
57:19	it without some really significant changes at the highest level well I agree with you and that's one of
57:26	the things that we're doing in the Aging field is to talk to politicians as well as the FDA to convince them that aging
57:32	is something that is important right now if you talk to most doctors even geriatricians who treat older people
57:39	aging is just the way it goes we've got to deal with it it's natural well you know when have we humans put up with
57:45	what's natural if we didn't want to everything else we we work on Aging is one of these things let's all live with
57:52	it but in at the political level uh I and my colleagues have talked to them it's slow you can't change the the
57:59	course of the Titanic too quickly but we do see things bending and the FDA has actually agreed that if we do certain
58:06	clinical trials for instance with metformin the diabetes drug that we think might slow aging if we can hit
58:12	certain endpoints and show things are actually working they are well prepared
58:17	to consider calling aging a treatable condition if not a disease that's right that we can prescribe medicines for
58:23	right um yeah I mean the the kind of underlying theme in the book and and in
58:29	your work is this idea that there is no biological law that we need to age like we just sort of accept that as a truism
58:35	but in fact you know that's that doesn't necessarily hold water
58:42	no no no nobody um has any reason to say that that we have this clock that that cannot be
58:49	changed in fact what we've learned going back to the Horvath clock is that about 80 percent of our lifestyle
58:57	um 80 of our health in Old ages due to our lifestyle and how we live right and only 20 is genetic and actually that
59:04	that's done uh by studying twins who you know some smoke some don't some live
59:09	differently stuff your genes are not your destiny that's the good news so that what that means is
59:16	it's up to you and if you want to be frail or to be honest dead at 80 go for
59:22	it we know how to do that do everything that that the marketing people want you to do eat the cake sit on your fat ass
59:29	and watch movies that'll get you there pretty quickly yeah but fortunately you know in part thanks to New Media like
59:36	this we can actually all talk about what we think are the ways to extend lifespan and and not be
59:42	frail in old age like my father I talk about him a lot I'm very proud of him as a Beacon of Hope at 80 he's still
59:49	running around like he's 25 he's got no EXO pains very sharp-minded using all
59:54	sorts of high-tech um lifting more weights than I can actually and our trainer who's currently
1:00:00	training the two of us together he says you know what uh I think my dad was dead lifting or was
1:00:06	it a something like 180 pounds something a lot and he said the last 80 year old that I trained was was learning how to
1:00:13	get out of a chair right yeah you uh you post uh something on Instagram he's like
1:00:18	you know in the in the squat machine or whatever like just killing it at 80. the
1:00:23	guy's in his second career he's had this kind of um you know Resurgence and vitality as a
1:00:30	result of finding new purpose and meaning and he's also somebody who's been on your kind of protocol for a
1:00:36	while at this point and to see him in the gym at 80 like crushing it it's it's very inspiring
1:00:43	well I think most of us can achieve that in life you know there will be unlucky people that of course diseases still hit
1:00:48	us but most of us are wasting our our lives uh because we're basically not not
1:00:54	you but most people uh don't think about their longevity they they think oh when I'm old I'll deal with that when it
1:01:01	comes but now in early in midlife is the time to invest because it'll pay off
1:01:06	dividends later in life we've done such a good job with medicine
1:01:11	and Pharma in increasing I mean you would probably disagree but in increasing lifespan but not so good
1:01:19	in terms of increasing Health span right like we now have to dodge all these bullets of Modern Life just to basically
1:01:26	you know counteract that genetic marker to extend our Vitality right through the
1:01:33	processed foods and the kind of you know luxury imperative that our culture you
1:01:38	know reaffirms and enforces like all of these things we have to kind of opt out of of of the you know dominant Paradigm
1:01:46	in order to kind of Thrive later in life yeah well the dominant Paradigm that's that's existed now for about 300 years
1:01:52	is that doctors treat diseases um they don't treat lifestyle typically
1:01:58	there are exceptions but mostly the doctors around where I work at these great hospitals uh you they only see
1:02:05	patients after they get sick and so the the aging process is already pretty
1:02:11	Advanced at that point and aging is let's not be the not silly about it aging is what's driving
1:02:18	cancer heart disease Alzheimer's it's the main cause of disease and disability on this planet it's not I mean the these
1:02:25	diseases are real but they're the end point of this process that we're working on but most doctors don't think about
1:02:30	aging they don't think about what got people to the the cliff in the first place and I call it whack-a-mole
1:02:37	medicine which is and this is all great I'm not criticizing my colleagues we do need medicines we need to treat diseases
1:02:42	but it's a little too late for a lot of people um and this whack-a-mole medicine leads
1:02:48	to the the Paradigm of uh come in with a disease will treat it hopefully fix it
1:02:54	kick you out the door wait till you get sick again come back and repeat until failure
1:03:00	let's talk a little bit about um the ethics of your work so we were talking about Australia you know if we
1:03:06	just look at what's happening there as as a symbol of of you know climate
1:03:12	change in action and I kind of you know degraded planet Earth and a certain trajectory that we're on and have been
1:03:17	on for some time um as somebody who you know by your own words said you know I'm concerned about
1:03:23	the climate just like everybody else you have this mission to extend
1:03:30	lifespan which inevitably is going to lead to population growth which is an
1:03:36	exacerbant to the climate change problem that we're trying to solve so let's kind of dig in to this and the implications
1:03:42	of like let's say you're successful and your colleagues are successful and we
1:03:48	get to a place where people can live to be 150 175 people are
1:03:55	I would I would imagine more likely to have more kids there's more people on the planet suddenly we have to sustain a
1:04:01	greater population and deal with these other problems that we so far to date haven't been so good at dealing with uh
1:04:09	so everything you said was right except one thing the healthier people are the less kids they have later in life so we
1:04:16	can now uh extend the healthy period of life and we think based on some animal studies extend fertility so women uh in
1:04:25	the future we'll be able to have kids much later in life and have have fewer fewer of them but let's look at the
1:04:32	planet uh we do have an issue on the planet of course we've been going on exponential growth for the last couple
1:04:37	hundred years for our species but it's it's not the Doomsday that we thought it was in the 1970s uh Malthus
1:04:45	um and the erlix uh used to panic make make all of us panic because they said that global population growth well about
1:04:51	you're running out of resources if you extrapolate this curve vertically of course we're all going to starve to
1:04:57	death um in the next 30 Years actually they thought by now we'd all be starving to to be fair but what's happening is that
1:05:04	uh what they didn't realize would happen I think most of us didn't predict is that as populations across the globe
1:05:10	become healthier they become wealthier when they're wealthier they become
1:05:15	healthier and then you lead you have women who become educated and women don't want to
1:05:22	have 15 kids they don't want to always be pregnant when you give them the choice they have you know just a few and
1:05:28	what we're seeing is particularly in Africa the rates of population growth are dramatically declining I was just in
1:05:34	Ugandan uh late last year and I was talking to the locals and I said uh you know tell me about your family oh my
1:05:41	grandparents 15 kids or 13 kids I exaggerate um I have five brothers and sisters what
1:05:47	about you oh we only want to have two because we want to give them an education that's happening across the
1:05:52	planet so we're you know I'm drawing these curves uh anyone who's listening can't see this but basically we're tapering
1:05:59	off this exponential growth we're going to max out according to the United Nations World Health Organization at
1:06:05	about 11 billion now that that's still a lot of people of course max out on on the resources no no the number of people
1:06:12	on the planet so it's already tapering off and we're going to hit a sustainable uh level and actually start to decline
1:06:19	in population based on projections why wouldn't we just continue to populate until we blow through that ceiling well
1:06:25	because it let's look at um even in the US actually population is going down and is barely a replacement
1:06:31	level in Western Europe it's declining couples on average are having less than two kids
1:06:37	and there's plenty of people who choose not to have kids yeah I mean this is one of Paul Hawkins big things when he in
1:06:44	his book drawdown one of the most powerful tools in the the war against climate change or the you know the the
1:06:51	battle to to solve this problem is educating girls the more we can educate girls in in the
1:06:57	developing World um they're less likely to you know have as many kids right exactly exactly so
1:07:04	we're going to help build some schools over in Kenya that if anyone who can see this risk Brand This reminds me every
1:07:09	day first of all how lucky I am with my family here in the US but also that
1:07:14	there are people on the other side of the planet that need our help but you're right being a woman in in the these
1:07:21	countries is the worst they're if they don't have a well left to walk you know thanks for to Justin Wren he's helping
1:07:27	with the wells those things giving them water giving them education that's part of the solution to the problem of
1:07:33	overpopulation and it doesn't initially make sense but what you just said rich
1:07:38	is the most important thing give women the choice to decide how many kids they have right
1:07:43	um conversely as a thought experiment let's say you could live 200 years and and a
1:07:49	you know a female's ability to reproduce extends way later into life you can have
1:07:56	these you know now it's sort of like you mature you have kids and then you kind of you know gray into your older years
1:08:02	but you could get like two cracks at this right like you could have kids and they grow up and you get older and then
1:08:08	you get a new career and you know then you could just hey let's do this again yeah right you I'm sure there'll be
1:08:14	people and we know people like that um I won't name names but I know a 98 year old who has uh a kid who's in their
1:08:21	70s and also in their 20s all right um anyway I'm proud of him he won't mind
1:08:27	me mentioning his name Norman Lear he's fantastic okay uh Norms are one of those guys but but most people don't do that
1:08:33	yeah but but what I'm saying is when you're not just extending the
1:08:39	number of years that you're around you're extending Your vitality into those years right so if you if you remain vital later in life like the idea
1:08:46	of having a child at at age 70 if you're operating the way you were when you were 40 it seems like not such a bad idea
1:08:54	thank you for saying that because this isn't about science fiction living to 170 and having
1:09:00	you know a third of the world in wheelchairs what we're talking about is is real life how much time do you want
1:09:07	to spend with your parents before they get sick how or do you want them to to spend another you know decade in a
1:09:14	nursing home before they die this is really personal uh but it also we've got to throw away our preconceptions of what
1:09:21	being old is why we talk about lead Hamilton in his 50s he's basically got the the body and the looks of someone
1:09:26	much much younger being 50 is not old anymore certainly 60 even 80 like my
1:09:31	father that's not old anymore if you take care of yourself you extrapolate that into the future there'll be a day
1:09:37	when being a hundred isn't old uh you know there'll still be people who don't take care of themselves and will be sick
1:09:43	at 60. that'll always happen but on average people will continue to live longer we've been on this uh trajectory
1:09:50	of of living healthier and being more youthful in our old age for the last few
1:09:55	hundred years and a child born today if we stay on that trajectory here in the US can expect not just hope but expect
1:10:02	to live to 104. okay that means that they'll still be healthy 80 and 90.
1:10:07	which is great it's all about keeping people healthier for the longest period and then dying relatively quickly
1:10:14	yeah when I was you know 10 years old if there was a Laird Hamill a 55 year old
1:10:19	Laird Hamilton doing what he was doing it would just be it would it would have blown people's minds right I mean not
1:10:25	that he doesn't blow people's minds now but that would just be the the craziest thing you'd ever heard of exactly so we
1:10:31	live in a Wonderful World um where people can learn about things that typically they'd never read about or
1:10:37	maybe they'd have to wait 20 years right my research I'm talking about it as it happens pretty much it's it's a crazy
1:10:43	world we live in but it's wonderful and also young people now have access to
1:10:49	information you go back to when we were kids how did we get information well there was the local library which was books that were basically old and musty
1:10:56	or you could go to World Book Encyclopedia or Encyclopedia Britannica and look up you know a paragraph of
1:11:02	something and this was all data and information that was old and not cutting
1:11:08	edge today you can learn about stuff that's happening and change your life based on things that we only dreamed
1:11:13	about as kids right um from a philosophical perspective and
1:11:19	like kind of playing playing on this thought experiment like let's say you could live 200 300 years uh
1:11:27	how does that impact the psychology of a young person's mind in terms of how they
1:11:33	make decisions about their career path or what they want their life to look like and we did talk
1:11:39	a little bit about this last time but I I'm interested in in how that impacts
1:11:45	like risk assessment right like if you're if you're like hey man I'm I'm 18 and I'm going to live to 300 uh you know
1:11:53	barring me getting hit by a bus like you know I have a lot of life to live so am
1:11:59	I really going to go skydiving because then the risk of that seems so much more
1:12:04	severe than it would if you're looking at well I'm going to only live to you know life short and I'm going to die at 80 anyway like I'm going to roll the
1:12:11	dice and take these risks and then how does that play out on a macro level in terms of what culture and society looks
1:12:17	like yeah well we're already on that path I don't think people in the 1840s
1:12:23	and 50s were worried about bicycle helmets if they had bicycles you know what I mean the longer we live the
1:12:28	healthier we are the more protective we are of our bodies and our children and that'll continue right now that we're
1:12:34	seeing a rubber banding with that with like Jonathan height and what he's doing in terms of like you know we need to rewild our kids because we're so worried
1:12:40	about we don't want them go outside without a helmet on oh I'd walk down the street it's extreme I just got back from Shanghai where uh there are cameras that
1:12:48	that shame you on billboards if you cross the street when the lights are oh really the red yeah
1:12:53	and it's and it's got how does it shame you it like a photo of your face yeah right on the street you can see the lady
1:12:58	that crossed the street uh this morning that uh disobeyed the rules and she apparently oh my God has demerit points
1:13:04	on her uh social her social score oh that's just like that's Black Mirror stuff right there yeah scary stuff
1:13:12	hopefully this world uh that we live in won't be like that anytime soon
1:13:17	but yeah the the the risks will you don't want to take massive risks but you know what I I think that we're we're
1:13:23	exaggerating maybe if we live for a million years we're going to be a little bit more cautious crossing the street
1:13:28	but I think that if we live to 150 say there are those of us who like taking risks anyway I don't think somebody says
1:13:35	I'm going to wait till I'm 90 to jump out of an airplane door in your 20 right so it's there were Risk Takers and most
1:13:42	of us will still take risks in life you know people actually funny funny aside is people think that I'm scared to die
1:13:48	because I'm working on Aging but anyone who's seen me drive my car knows that that's not true I'm a big risk taker
1:13:55	unfortunately on the road I'm not well not anymore I'm now a bit sedated but I shouldn't say sedated uh but I'm I'm
1:14:02	more uh calm about my driving but I do Drive but
1:14:10	but I do like I do like the feeling of risk and it's the reason that I'm in this career in the first place because I
1:14:16	took a lot of risks when I was young to get here um point being
1:14:21	you know maybe I'll live to 100 maybe I'll live 150 I don't know maybe I'll die tomorrow I don't care I I like doing things that
1:14:30	are novel I like doing things that are risky and I think that a lot of us will still do that no matter how long we're
1:14:36	going to live but I think the trend in in the world is that the longer we live the more uh
1:14:42	scared we become of of danger right fireworks are we gonna worry about
1:14:47	fireworks yeah that kind of thing um but I'm not so worried I think that these are small prices to pay for a
1:14:55	world that is different from today as we are from 1840 London yeah
1:15:01	I think in tandem with trying to elongate life's lifespan and health span
1:15:10	you know we also have to solve these other kind of you know cultural dilemmas that
1:15:15	we find ourselves in that are contributing to mental Decline and emotional decline the disconnection the
1:15:22	you know addiction to technology the you know lack of purpose that underscores
1:15:27	most people's lives and we talked about this last time too like how does the how does like the work of Dan buettner and
1:15:32	the blue zones kind of intersect with your own work you know ultimately what's the point in living so long if you know
1:15:40	our value system is is you know not in alignment with you know what's required
1:15:46	to be fulfilled and to be happy and to have you know purpose for living that
1:15:52	long Yeah a hundred percent so there's the there's the world of molecules and
1:15:57	genes that that I do for my day job but I'm also very passionate about finding
1:16:03	Mission and purpose and doing the best you can in life um because that that's also what I what
1:16:09	drives me um and so I think you're right but if if you're someone who's prone to depression
1:16:15	giving up giving up hope uh you've got to get out of that you've got to find what excites you what drives you I teach
1:16:23	a lot of students at Harvard and there are some students who are very smart you know some of the best brightest in the
1:16:29	world but they're I'm not sure I can do that you know whining around I'm gonna I can't slap them around find
1:16:37	a goal go for it this is your opportunity and don't come to me with an
1:16:42	experiment that'll Advance Signs by one step come to me with with an experiment
1:16:48	or a question that'll Advance US 20 years into the future now that's not easy right that's the hardest part of
1:16:54	science the rest is just manipulating chemicals it's finding something that you wanna
1:17:00	go for and change the world and that's that's what I think has been if I have a
1:17:05	secret to success besides a lot of luck and hard work it's at age four having a goal and going for
1:17:12	it yeah it is interesting that that it dates all the way back you know your whole life has been infused with this
1:17:18	you know this drive this passion to you know solve this problem or you know yeah make no Advance Humanity
1:17:25	in this way well you know it makes a good story and of course looking back on it it looks pretty easy but there were
1:17:31	there still are plenty of times where I wonder you know do I really have to get out of bed today this is tough you
1:17:37	know ups and downs and I say that because uh anyone who who experiences this and
1:17:44	has adversity they have to know that that's part of the process you don't grow you don't learn you don't succeed
1:17:51	unless you go through that and it never ends right I'm not writing High I still have massive ups and downs and obstacles
1:17:58	even at my age but I've learned actually that if you have a goal that's what gets
1:18:04	you through it so when it's all said and done like what is the what is the Legacy that you're
1:18:09	working to leave behind like what when you when when when you're complete
1:18:15	what does it look like ideally uh well of course that's never going to happen
1:18:21	um but you hold this great vision so what is that Vision well I would love to to have a time machine to go
1:18:28	a few hundred years into the future and if I see a future where people are
1:18:34	able to do multiple careers with you we're talking about career arcs I mean
1:18:39	what about a world where if you know not everyone can can have their dream job
1:18:44	initially I would love a world where people can live to 150 expect to be still playing
1:18:50	tennis 120 I think it's doable there's no reason why we can't do that with our Ingenuity but what that gives you is the
1:18:57	time to have multiple careers multiple lives multiple partners if you want
1:19:04	um although you may find the right one in the beginning but but this gives you you know let's let's go back in time a
1:19:09	little bit in 1840. okay that person uh who's born in
1:19:15	1840 was not expecting to have uh first of all um a great time at age 40 or 50
1:19:21	basically you're worn out by then they don't expect to have multiple careers they didn't have the opportunity anyway
1:19:27	so if you extrapolate from there to now and into the future just as much what you have a world is where even if you
1:19:33	you're dealt the wrong cards at the beginning of Life you have multiple chances to correct that there are some
1:19:39	risks to take of course um and you do need some support you know I'm not running for president I
1:19:45	couldn't I was born in the wrong country but what I would love to have is what I call a skill radical which is well it's
1:19:52	another chance it's if you're busting rocks or whatever it's that you hate um
1:19:57	two years off retrain get another chance and if you have a long life that's 150 years long
1:20:03	you can do you know one career could last 20 30 years become the best you can
1:20:09	be at that and then switch and that that's a life that would be well lived
1:20:14	wouldn't it yeah I think it would it would give people
1:20:19	the patience that I think we lack right now like every we're in such a hurry from the
1:20:25	moment we're born you know it's a it's a habit trail of achievement and measuring
1:20:30	ourselves against others and you know from the moment you enter junior high
1:20:35	school and then it's grades in high school and it's getting into cut like you're it's this race right and the
1:20:42	Brain and the emotional body isn't mature enough to really process that to make the best decisions how are you supposed
1:20:48	to I mean you knew what you wanted to do at a very young age most people don't right but they're kind of you know
1:20:54	corralled into a certain path and on a trajectory that for a lot of people they
1:20:59	don't it's like a waking dream that they don't kind of come to out of until they're 40 and think why am I even in
1:21:06	this position but if we could slow things down and say hey you're going to live to 150
1:21:12	no big rush here like take your time go on a kibbutz you know maybe there's a
1:21:18	national you know sort of period of time where you're you're you know of service or you do some kind of Teach for America
1:21:24	like programs like that that allow people to mature and develop the
1:21:30	self-awareness and a sense of the world so that they can make that decision about how they can best contribute and
1:21:37	Find meaning and purpose in their lives rather than being in such a rush yeah I couldn't have said it better you
1:21:43	take someone like my father who at 70 thought he had a few good years left he'd be getting Dementia by this point
1:21:50	he wasn't looking forward to the future late 70s is still perfectly fit what am
1:21:55	I going to do with my life he started a new career right and so instead of being you know late part of your life what's
1:22:02	my legacy we can turn that into why don't I just begin a new one and you
1:22:07	know I'm now 50 you know what it's like normally we should be if anything was
1:22:12	right if we look at our parents and their grandparents their parents 50 is the time when you like oh
1:22:18	I'm almost done wind down right it that's not how the world is these days
1:22:23	and in the future it'll be even better we're at 50 you're like I'm just getting good at this I just understand how the
1:22:28	world Works although you never fully get it I I don't feel any different than I did when I was 30. I have a bit of more
1:22:34	wisdom of course but everything else is the same physically mentally and hopefully a greater appreciation for
1:22:41	the wisdom of the elderly rather than just warehousing them in nursing homes and and trying to put them out of our
1:22:48	line of sight and and you know dismiss them which is the tragic situation that we're in now yeah it is that I the older
1:22:55	you get actually the more you appreciate the these folks uh what I want is a world where people in their 80s and 90s
1:23:02	are not just appreciated but they're actually utilized if they're healthy they can be advising or running
1:23:08	companies or motivating the youth right that's the world that I want because it
1:23:13	once you're in a wheelchair or in a nursing home then you're done for and of course young people are not going to
1:23:19	want to spend their time listening to people who have dementia but in a world where you can have a mentor who's seen
1:23:25	90 years of really interesting stuff how cool is that the flip side of that is
1:23:30	and we touched on this last time is the 120 year old who's still on the Supreme Court and lacks the sort of plasticity
1:23:37	that kind of adapt to you know modern times who's stuck in an era that is that
1:23:43	is bygone and thus is despite their wisdom and experience of the ages isn't
1:23:49	it in lockstep with what's actually happening right I mean that seems to be a potential downside of this it's not
1:23:55	perfect it's not perfect right there'll still be people who who are in positions when they're too old to deal with right
1:24:01	but now it's like finally that you know these people are we're getting rid of all these people so we can get fresh
1:24:06	blood in here in A New Perspective I don't agree with that at all I think that we should treasure those folks that
1:24:12	have the wisdom and experience because what history is really the way to
1:24:17	predict the future and they've seen it all right that someone like a Warren Buffett I mean I would love to keep him
1:24:23	around for a lot longer because someone like that it does a lot of great things but you know yeah Bill Gates same there
1:24:30	are people you want to keep around maybe there are a few that we don't but these are the prices to pay for a world where
1:24:36	the majority of us can expect to be playing tennis on our 80th birthdays
1:24:41	right um as a result of doing this book tour I would imagine you've probably met some
1:24:47	pretty interesting people I would imagine there's some pretty cool people reaching out to you yeah yeah you're going to be cagey about
1:24:54	this right well yeah yeah I mean it's it's you know look we all you know we
1:24:59	all we all want to extend our lifespan and this book has been very successful and you've been out talking about it so
1:25:07	um I would imagine that that's created some interesting encounters for you yeah well I that's part of the the
1:25:15	joy that I have every day is um I've learned that people are really interesting yeah
1:25:21	um as a teenager I didn't go to medicine because I thought humans were the the evil on the planet I've kind of switched
1:25:26	it around and realized that you can learn a lot just by listening I'm talking today but usually I'm quite
1:25:32	quite quiet uh I don't name drop but but I've I've met a lot of my Idols in business in
1:25:39	Hollywood a lot of billionaires I probably met a
1:25:44	quarter of the billionaires at this point yes but they're I'm learning a lot of the Ponce de Leon right yeah well you
1:25:51	know I'm I am a spokesperson for this field um but I I should say that there are
1:25:58	hundreds of scientists like me working away every day to help uh solve this
1:26:03	problem um of course the one thing that everyone wants to know and wants to talk to you
1:26:08	about is okay you're the guy who's steeped in this but like what do you actually do and what's interesting you
1:26:15	know in in hearing other interviews with you and the last time we spoke Etc and in the book is that you're very quick to
1:26:22	say and very certain to say look I'm not I'm not a medical doctor and I'm not gonna you know give you a prescription
1:26:27	for your life and I'm not going to give you advice about you know certain protocols and it's not until you get to
1:26:34	the conclusion of the book where you actually say actually here but I will tell you a few things about what I do and it's literally like a page
1:26:41	in the entire book right so I'm interested in why you because I
1:26:47	would imagine in most interviews that this question gets asked right this is what people they're like what do you do like you're the one who knows more about
1:26:52	this than almost anybody so tell me what your habits are right well I didn't do it intentionally
1:26:58	uh but as it's worked out worked out is that those who make it to the end of the book get the reward right okay there it
1:27:05	is that's not why I did it um it's actually more that I'm in a an unusual position right I'm a
1:27:12	Harvard Professor I'm supposed to be World leading scientists and scientists are like monks
1:27:18	monks don't go around telling people that well actually they do but scientists shouldn't go around
1:27:24	telling people how to live their lives I'm I'm part of this monastic group of
1:27:30	people that are should only say something if it's factual right and I
1:27:36	try my best to do that the supplements that that I admit that I take and that's rare for a scientists to
1:27:42	admit that stuff even though probably about half my colleagues are doing something I'm out on a limb
1:27:48	um now anyone who wants to jump to the page that Rich talked about is page three pages 304. yeah I get asked that a
1:27:56	lot yeah oh do you yeah that's so funny but but I've realized that uh there's a
1:28:01	lot of demand for knowledge about this and so what I've done is I've got a newsletter
1:28:06	and so I'm updating people people can subscribe if they'd like it's at lifespanbook.com and so I'm adding to
1:28:14	those pages now it's not just one page to be fair that the whole of part two is
1:28:19	about what you can do in terms of fasting and exercise and why it works or you just kind of break it down and hear
1:28:25	other things well this is that's the cheat sheet yeah towards the end uh but yeah like I can't run around
1:28:31	saying take this supplement or that brand is good I will first of all I'll lose my credibility I've got to be
1:28:37	objective also I don't spend my time testing products that's not what I do I'm a molecular biologist geneticist
1:28:44	um but I'm I'm willing to go out on a limb and say what I do and what works and how I think you
1:28:50	should not should but can adapt your life the other thing that it I hope everybody
1:28:55	realizes is that what I do is a guide it's not proven to work but I've got the
1:29:02	reason the book is full of references is if somebody wants to do a deep dive into a subject whether it's fasting or the
1:29:09	cold or sauna bathing or supplements there's a lot of other
1:29:14	scientific work that they can delve into as well yeah the notes I mean the notes
1:29:20	go on for however many pay 360. yeah so like 50 pages of notes at the
1:29:26	end right so you know I'm trained as a scientist and everything in that book was fact checked to the nth degree and
1:29:32	with references and that's why when you read my book versus maybe some others
1:29:37	that are that are not written by scientists you can bet that what you're reading is factual as far as We Know
1:29:43	well let's talk about what it is that you do like let's in your estimation like what are the most important things
1:29:49	that and and again you can preface this whatever with whatever caveats you want but like what do you think are the most
1:29:55	important things that people should be doing or looking after on a daily basis to kind of you know take out an
1:30:01	insurance policy against aging given the current state of knowledge and
1:30:06	understanding that's well put okay now I feel free to speak because I don't endorse and I don't recommend
1:30:12	um I think the most important thing for anybody
1:30:17	to live healthier for longer if there was just one thing I could say it would be eat less often don't eat three meals
1:30:25	a day I I literally think that that people who recommend three meals plus snacks trying
1:30:31	to keep your glucose levels always at a pretty high level are doing the world of disservice
1:30:37	um and I'm going to go out on a limb to say that a lot of nutritionists would disagree with me but I've been doing this for 30 years
1:30:42	I've seen what happens to people and animals when you restrict their food and it it's all good I mean you don't want
1:30:49	malnutrition or starvation of course but putting the body in a state of want every day
1:30:55	um for as long as you can do it I do it you know like I said hopefully till late afternoon dinner the that's the easiest
1:31:01	and best thing you can do other things are the high intensity interval training or jumping up and down with weights in a
1:31:08	swimming pool almost drowning that's pretty good right you're going back tomorrow right yeah well I will do it
1:31:13	again actually now I'm I actually think I know not to go too far into the deep end uh but but honestly we now know
1:31:22	we all have the the power with the scientific basis to actually live at
1:31:28	least 15 years longer okay so there are actually and I I talked about this I think on Twitter recently that there are
1:31:35	there are five things that are pretty obvious and easy to do uh that'll give
1:31:40	you 15 years and that's just off the top of of my head things like you know
1:31:46	exercise the fasting don't eat too much eat the right Foods try to be plant-based
1:31:53	get sleep have social network that gives you 15 years that's amazing that's not
1:31:59	even going delving deep into my book which takes it to another level of what the best exercise and supplements
1:32:06	probably are so that's the good news I do list a lot of things we could we
1:32:11	could talk for hours about what I do page 304 you'll see more I'm conscious that we have a microbiome
1:32:17	that is that needs to be healthy so I make my own special uh yogurt which I mix my Resveratrol in
1:32:25	I think I'll release the recipe of that pretty soon to the in the newsletter if anyone would like to make it
1:32:32	so that these are the things um on the uh sorry to interject but on the you sure sort of said you know eating
1:32:40	eating plant-based predominantly plant-based I mean a lot of that is is
1:32:45	informed by the relationship between excessive protein intake and that the that impact
1:32:53	on Aging correct well from your from your perspective in the work that you're doing so the so the plant-based food
1:33:00	um I think a little bit of meat's fine especially if you work out and you're trying to build up bulk up some muscle but I think that what we've learned is
1:33:06	by studying the sardinians and the okinawans is that those diets are the
1:33:12	best for for humans and they are mostly plant-based with a little bit of meat like fish so why does that work okay why
1:33:18	do we think that works the two reasons one is that you don't want to overload on some types of amino acids which
1:33:25	you'll find in me uh leucine isoleucine valine these are turn off our bodies defenses through a
1:33:32	pro pathway called mtor um they'll probably be a Nobel Prize awarded for that stuff by the way it's
1:33:38	big deal mtor but if you're always eating a lot of protein in terms of meat
1:33:44	uh then you'll you'll never really optimize your body's defenses so I try to be plant-based foods but there's
1:33:51	another thing that that most people Miss which is the Xeno hermetic molecules from Plants you get those you don't get
1:33:57	those from meat as much so what do you make of the carnivore diet yeah I'm on this I'm on the other side
1:34:05	it is an interesting phenomenon just like sort of culturally to go how did this suddenly happen and there's a
1:34:12	cohort of people who are all about just that's all they eat right this hasn't been going on for very long the story
1:34:18	very much has yet to be fully told um but you know if somebody's listening
1:34:25	to this and perhaps was flirting with the idea of that I mean to to you know what what would be your response to that
1:34:31	person all right well so I'm a scientist so let's talk some science uh briefly the what what you do when you
1:34:38	activate this mtor pathway is you're telling your cells in your body that
1:34:44	times are good you've just caught a mammoth okay basically and Now's the Time to build your body and actually fix
1:34:52	things uh heal things and grow and it turns out that there are there are two
1:34:57	things your body can do there's grow and then there's on the other hand the other
1:35:03	side of the balance is to protect growth protect growth protect and if you're
1:35:09	always in this growth mode by telling your body Now's the Time you got your amino acids grow that's great when
1:35:15	you're young and middle age you'll bulk up right you'll feel good you'll actually burn energy more you'll lose
1:35:21	bit of fat but long term you're going to sacrifice your longevity in my view because you're
1:35:28	not turning on your body's defenses which typically are turned on when your body senses that there's adversity
1:35:33	there's a need yeah so being hungry and eating plants are going to be telling your body times
1:35:41	are not as good we've run out of Mammoth meat let's hunker down but you could say we're on our own we're on our own so
1:35:47	we're gonna have to you know do the heavy lifting here it's it's basically catalyzing these systems these
1:35:53	biological systems to protect the body right yeah and and in turn promote
1:35:59	longevity versus oh this we got an endless supply of food coming in here we can just shut everything down because we
1:36:05	don't have to worry about it right think of it this way when we're young our defenses are on hyper alert our bodies
1:36:11	don't get diseases you don't find babies with Alzheimer's disease their cells know how to repair uh and and defend
1:36:17	against issues by eating a lot of meat I think what you're likely to be doing is
1:36:24	accelerating that process towards older age so because your body will uh yeah be
1:36:31	in a growth state but you won't be turning on your body's defenses and actually as you get older your defenses
1:36:37	go down and down and down and that's one of the main reasons that we end up getting old right okay so you gotta get
1:36:43	your defenses up like you're a baby speaking of which I've been on on a much
1:36:48	healthier diet the last few years including intermittent fasting including the supplements that I've got written on
1:36:54	page 304 one of the people say oh I'm not noticing anything after you know maybe
1:37:00	two weeks on the on supplement of course you're not going to see that I've been doing it for some of them for 10 years
1:37:05	but what I've noticed most recently with my current lifestyle all of these things combined biggest things that has changed for me
1:37:12	is that I don't get sick anymore that's amazing I used to be the kind of guy that would go from one cold to
1:37:18	another I even had a sniffle in years I can't remember last time I had a cold and I'm on planes people are sneezing on
1:37:24	me I'm shaking hands of people pretty much all the time so my immune system must be on hyper
1:37:30	alert and why is that good if you ask a centenarian
1:37:35	what about your younger years in your 50s 60s they'll say I never got sick never got a cold my father's like that
1:37:42	he doesn't get colds either yeah what about sleep have you looked at the
1:37:47	impact of sleep on all of this some people have uh well it we've done a little bit in mice what we've discovered
1:37:53	is that the sirtuins that we work on these protectors that respond to the NAD
1:37:59	levels in our body they cycle through the day and they're actually controlling our sleep wake
1:38:06	cycle that's really fascinating because what it means is that longevity protectors these adversity sensing genes
1:38:13	are also controlling our body's clock and if you're screwing up your longevity defenses
1:38:20	you're also probably screwing up your body's clock so another side effect that I get with this new lifestyle is I get
1:38:27	much better sleep and I know that um you know we've got rings that can tell us that now and I feel great I
1:38:33	don't wake up tired anymore the so this MPT Gene we talked about
1:38:38	earlier the one that makes NAD that's actually going up and down in levels throughout the day it goes up in
1:38:44	the morning down it's changing the NAD levels and uh and if you get that out of
1:38:50	whack we get this thing we call jet lag and another side effect actually I find it anecdotally it's not proven is that
1:38:57	if I raise my NAD levels either by fasting exercising or taking a supplement
1:39:03	I don't get the effects of jet lag that's interesting wow
1:39:08	that's super interesting um all right so fasting
1:39:13	trying to create some hormesis in your life basically living a blue Zone's lifestyle
1:39:21	in terms of supplementation you're I know you're not going to give like
1:39:26	you know specific recommendations but basically walking through what you do you take a daily Resveratrol you take an
1:39:36	nmn supplement which is basically a supplement oriented around promoting NAD correct correct a different version of
1:39:43	that would be NR right which is like one step removed from that same process yeah
1:39:48	so the Buddy uses NR which is short for nicotinamide riboside it'll
1:39:54	convert NR into nmn and then nmn into NAD and that last step uh no that first
1:40:00	step is this npt Gene okay so yeah you can people are taking an r or they're taking nmn NR is a little cheaper than
1:40:08	anime I've studied nmn people ask me why not in our well nmn first of all is more
1:40:14	stable on the Shelf so that's good but also I find that it produces some better
1:40:20	effects in mice when say for endurance but uh the truth is even though there's
1:40:26	a lot of chatter on the internet and some of my colleagues have their stakes in some companies I by the way I don't
1:40:32	benefit from any supplements ever so I have no stake in this uh but some of my
1:40:37	colleagues and on the internet they're saying oh one is better than the other the truth is we really don't know yet
1:40:42	which is better or if if they're the same I I take enaman because a I have a ready supply because we're doing
1:40:48	clinical trials but also uh because I've studied it the most and that's it right there's no other are
1:40:55	you is there anything else that you're taking yeah yeah there's a there's a bit of a list I'm also taking a drug
1:41:03	oh a drug right a drug called metformin which is yeah
1:41:08	um so metformin has been around since the 1970s and been in tens of millions of people it's relatively safe it's not
1:41:14	perfect it's not totally risk-free but most people what they experience is an
1:41:20	upset stomach and a lack of appetite uh which can be mitigated by a slow release tablet you do need a doctor's
1:41:26	prescription in the US to get it or in Canada or in Australia or the UK or other parts of the world uh you can just
1:41:32	go buy it at a pharmacy because it's on the list of the world health organizations list of essential medicines for Humanity
1:41:39	so what prompted you to get on Metformin oh yeah really simple um my best friend told me to uh to take
1:41:46	it no but uh in all seriousness so his name's Neil brazilai he's considered the world's expert in this but you know I
1:41:52	don't just do it my friends say I have to research this so I looked at the literature and there were a couple of
1:41:58	studies that I cite in the book they're worth reading don't just take my word for it if you look at over a hundred
1:42:04	thousand people in some cases they're veterans but mostly older people of all walks of life who have taken
1:42:11	metformin because of their type 2 diabetes high blood sugar if you look at other diseases over the
1:42:17	next I think it's five years time those that have a high risk of Alzheimer's who
1:42:23	don't take Metformin have a much higher risk of alzheimer's than those that took metformin and the same is true for some
1:42:30	cancers and Frailty um and heart disease so what is that
1:42:35	interplay like why would that be the case right well there's a lot of debate about how metformin works the the main
1:42:42	explanation is that there's an enzyme called ampk or amp kinase that talk to
1:42:48	the sirtuin so they're actually interplay and actually mtor so there are three main anti-aging Pathways I've
1:42:55	talked about Saturns that we worked on in yeast and now in mammals the middle one is the ampk which metformin works on
1:43:02	and then this mtor which responds to low amounts of protein and they all talk to
1:43:07	each other so we used to fight as scientists my pathway is more important than your pathway blah blah and it was vicious people were trying to kill each
1:43:13	other now we realize that there's a network and if you tweak one you can tweak the you'll tweak the other
1:43:18	but I think what the best is to to tweak them both just at moderate levels and
1:43:24	get the best anyway mpk what it does to the body is it for one thing main thing
1:43:30	is it ramps up energy production mitochondrial activity it's called and mitochondria most people may have heard
1:43:37	are the battery packs of the cell and the more you exercise and if you fast calorie restrict you'll have more
1:43:43	mitochondria that's a good thing that as far as I know there's you can't have too many mitochondria that's the key to
1:43:50	being a good endurance athlete mitochondrial density it is it really is and actually as we
1:43:55	get older uh we lose about half of our mitochondria um but one way to boost that is to take
1:44:02	Metformin or to uh to do these other things like exercise but it's not all good news
1:44:07	um there are some studies that show that metformin can interfere with endurance and muscle
1:44:12	um hypotrophy and there's been a lot of talk about it actually on the internet Peter Atia has
1:44:18	done some some work podcasts on this um Neo bars a lie my good friend at
1:44:23	Albert Einstein College of Medicine was on that study so I I called him up and I said what's the skinny on this tell me
1:44:29	and he said it's overblown and so when you look at the data um and I'm going to be using my hands
1:44:35	for graphs but basically the the two bar graphs are overlapping there's some
1:44:40	minor differences but there are plenty of people in that study that took metformin that gain more muscle than
1:44:46	those that didn't but overall on average there was a slight very slight uh increase in muscle mass in those that
1:44:52	weren't taking metformin and doing weights but there were benefits to the metformin there was lower inflammation
1:44:59	lower oxidative stress in the people that took the drug so what do I think is the take-home message number one don't panic if you're
1:45:07	an average person if you don't make a living from bodybuilding it's not going to matter that much but in an abundance
1:45:14	of caution what I do is I don't take Metformin on days I work out pretty simple solution
1:45:20	but I still think on days where I'm not working out metformin is going to protect me against these major diseases
1:45:26	so your impetus to get on Metformin didn't have to do with elevated blood
1:45:32	glucose or or insulin resistance it was pure it was more from this sort of longevity self-experiment perspective
1:45:39	well it's both you know there's never one answer to these things my father and
1:45:44	his father were and myself were susceptible to obesity and diabetes I'd be I'd be twice my weight if I ate what
1:45:51	I felt like eating and my son struggles with this a lot he's 12 and already struggling so we've got obesity genes
1:45:58	and my father went on Metformin years ago and I think is one of the reasons he's probably still healthy
1:46:05	so that's that's also a factor no question that I took that into account I didn't take Metformin
1:46:12	um before I got diabetes until recently uh because I just wasn't sure it was worth the risk versus the reward but
1:46:19	when I dug into the science of this it was a no-brainer the risk for me is very low the worst that I get is an upset
1:46:25	stomach and actually I feel less hungry so that's a side effect that I like and then on the upside is some of the
1:46:32	chances of getting I forget which type of cancer but it's in the book can be lowered by 40 percent
1:46:38	that that's a massive massive effect so you always got to balance it so I don't prescribe anything to people but what I
1:46:45	would recommend to do is to think what risk am I willing to take
1:46:51	uh what are the potential downsides and with a drug that's been in millions of people there's a risk but the risk is pretty
1:46:57	low how old am I you know if I if I'm 110 I've probably only got two more years so
1:47:03	what what's that lose so that's obviously a calculation um and then uh you know how expensive is
1:47:11	it right some some of these things are still just very new to the market and all of that has led to me uh adapting my
1:47:19	life over the years admittedly some of these discoveries are fairly new so I haven't been doing them longer than I I
1:47:25	would have preferred to have done them earlier um but that's the calculation and so I I think that we all know what's going to
1:47:32	happen in the end if we don't do anything if we just sit around and do what you know we think feels
1:47:39	comfortable the end is not pretty I've seen what happens um the other thing that that I want to
1:47:45	talk about or just mention at least is is smoking so my mother died of lung cancer it was brutal to see her pass
1:47:51	away and she had a lung removed right she did and then her final one gave out 20 years later
1:47:57	um so she lived for 20 years on one lung she did she managed to live a pretty
1:48:04	good life she visited about 18 countries after that but the way that she passed away I don't
1:48:11	know have you ever seen someone die no uh not in that way yeah I've never seen
1:48:17	someone uh die except for my mother but she basically was was drowning in her own fluid wow and uh it happened pretty
1:48:25	quickly so all I had a chance to do was to whisper in her ear while she was choking to death that I wanted to thank
1:48:31	her for being the best mother she I could ever hoped for now a lot of people die like that do not smoke if you smoke
1:48:36	please please try to give up because it's not pretty and not only are you increasing your chance of lung cancer
1:48:43	smoking will Aid you we know that that clock the Horvath clock is accelerated
1:48:48	by smoking because it's damaging the DNA and distracting the distracting The Pianist yeah
1:48:55	if you could what is what's the study that you would like to see perform like if you could design
1:49:01	you know the perfect human trial for example where you could do whatever you
1:49:07	want what would that look like and what would you hope to establish
1:49:13	well we I don't have to imagine that we're doing design one well so I mentioned near again nearby
1:49:19	he and a number of scientists have devised a study that the FDA has
1:49:24	approved as being reasonable test of whether you can slow aging down it's going to involve
1:49:30	hundreds of people and a few hospitals around the country it's called t-a-m-e or tame
1:49:36	what is a target targeting aging with metformin something anyway so that's getting underway that I
1:49:44	think is a very good start the idea is to take people who are elderly who are not yet sick and monitor
1:49:51	them over a period of five years and test their Frailty and their susceptibility to diseases and if we're
1:49:57	right we'll be able to show with those numbers of people that eight o'clock is slowed down but B that they remain
1:50:03	healthier because of in this case metformin but you know if I had a
1:50:08	billion dollars I'd take the top 15 drugs or molecules or supplements and
1:50:15	test those as well because otherwise all we're left with is you know what we're doing just trying to figure this out
1:50:21	ourselves and what's going on in your lab right now
1:50:26	it's pretty darn exciting I gotta say I'm very privileged to run a lab
1:50:31	um there are good days and bad days but most good days are my students are every few days coming to
1:50:37	me saying it's finally worked we've had a breakthrough so for instance we've had this breakthrough in reducing the cost
1:50:44	of this clock maybe we'll bring it down to five five bucks that's a great breakthrough that keeps me happy
1:50:49	uh the big thing is is reprogramming we've now gone from slowing down aging
1:50:55	with resveratrol and NAD boosters uh reversing some aspects of Aging like
1:51:01	endurance in in mice and hopefully people but the big thing that's just happened over the last couple of years in the lab
1:51:07	and increasingly excitingly in the lab is the ability to replace The
1:51:13	Pianist that's gone demented and reset the clock and get get it to go backwards
1:51:18	so we we've put this paper online and anybody in anywhere in the world can look at it if you'd like you can go to a
1:51:25	place called bio archive bio rxiv okay
1:51:31	um if you type in reprogramming in my name Sinclair you'll probably find it too we'll link it up in the show notes
1:51:36	great so we're very proud of that that paper which is still under review so it hasn't hit the media actually I gotta
1:51:44	say I know I'm rambling here but podcasts are a fantastic way of getting news out before the actual news before I
1:51:49	figure it out so you're hearing it here first but we hope that by uh sometime
1:51:55	early this year maybe by June we'll have this published we were revising it for
1:52:00	the journal Nature which is the one of the top in the world we're excited that we got good reviews from our colleagues
1:52:05	who do blind or Anonymous peer review that's a long way of saying we are
1:52:10	pushing the boundary of this reprogramming method uh just a quickly and the abstract of that study is what
1:52:16	yeah yes yeah so the summary is that uh those methyl groups that are counting
1:52:22	that we use to count the clock uh we can tell the cell to remove the right ones
1:52:28	so that they that the cell remembers how to play its genome correctly like it was young there are three genes that we we
1:52:35	take from um out of the book of embryo so when you're an embryo you're using three
1:52:40	particular genes to to grow and be healthy they get Switched Off by the time where young adults uh even while
1:52:48	we're babies if you put them back in just at the right time the right place at the right moment
1:52:53	we found that it's it's Ro we don't see any safety issues so that's the good thing what we see is the clock gets
1:52:59	wound backwards those methyl groups go back long story short the cells are
1:53:05	reprogrammed to be young again completely not just a little bit not two percent not two years but we can take it for
1:53:12	example in this paper you'll see if you if anyone looks at it can take mice that
1:53:17	have gone blind from old age if we put these three genes into the eye and turn them on for a few weeks their
1:53:24	Vision comes back as though they were young again what that tells me is that a lot of what we regard as a one-way
1:53:30	Street in aging is reversible if we can restore our eyesight what else can we reverse I mean that's got to be
1:53:37	about as exciting as it gets right I mean that's I've seen a lot pretty remarkable amazing wow and and our
1:53:44	colleagues and I have to create it we have a lot of help I don't know my way around a mouse as I to save my life but
1:53:49	our colleagues that did these experiments with us they're Blown Away my colleague Bruce Cassandra at Mass Eye
1:53:55	and Ear Hospital in Boston he called me up at 10 30 at night and he said David you wouldn't believe what we've just
1:54:01	seen uh excuse the pun we've got restoration of vision I want to run down
1:54:07	tomorrow and tell the FDA this is possible because right now degenerative eye diseases like glaucoma medical
1:54:12	generation these are not reversible the best you can do is slow them down slightly anyway that that's a whole story but what we're now trying to
1:54:19	figure out in my lab is how is it possible to reset the cell how does that work and where is the reset
1:54:26	switch what what's the repository of the information put another way was the backup hard drive of the cell
1:54:33	right so when that analog system gets scratched there's an ability to reboot
1:54:40	it with you know a digital replicant that is perfect yes and we don't know
1:54:46	where that information resides we know we can tap into it by using these three genes called O S and K for short but how
1:54:53	that works and where it goes to find the old information to be young it could be
1:54:58	a chemical on the DNA it could be a protein that sticks to DNA for our whole lives we're actively searching and so
1:55:04	we've got a whole bunch of very smart people in my lab look working hard on that and obviously you know human beings are
1:55:11	infinitely more complex than mice but what can you extrapolate from that to
1:55:16	give you confidence about applicability in in a human context right well we we don't know but we we do
1:55:25	work in human cells so we can take human neurons and grow them make a mini brain in the dish
1:55:31	and we can both accelerate aging um make The Pianist demented in those
1:55:36	cells and we can reverse the age of those cells and make them grow again like they were young so we've done it what we say in vitro um
1:55:43	in the dish uh we've done it in mice our eyes and our biological systems aren't any
1:55:50	different than our Mouse is really so I'm optimistic you know but until we
1:55:55	know in humans that we can do this I can't declare Victory so what I'm doing as I typically do is try to spin out the
1:56:02	technology get it into patients as safely and as fast as possible
1:56:07	but in hopefully in the next few years we'll have the first patient tested and the results will be pretty quick this
1:56:13	isn't like a long-term longevity study if we can restore Vision to a patient with glaucoma we should know within a
1:56:19	few weeks and I would imagine that I mean basically you're dealing with a reversal
1:56:25	mechanism so there's no reason to believe that it would only be operational in you know in in the optic
1:56:32	context like it should it should be applicable across the board or in other you know within respect to other
1:56:37	problems you are exactly right we didn't choose the eye because it was easy we chose it because it was hard and uh
1:56:43	because the eye gets old very quickly if you damage your eyes I'm going to grow back like your skin so we thought let's
1:56:49	go for it my student Wan Chang Lu is a brave brave student um so if we can do that to the eye I'm
1:56:55	much more optimistic that that these other organs and systems whether it be a
1:57:01	kidney that's failing or a liver skin who knows we're going to test that
1:57:06	rigorously uh we can even try to reprogram the entire animal we've
1:57:11	started doing that one of the now you're just getting crazy right well you got to
1:57:16	do it I'm sure everyone else wants to know the answer but but here's what's holding us back in in the technology
1:57:24	the ability to deliver genes is not as easy as everyone thinks they are it is right now there are some drugs on the
1:57:31	market that can actually fix genetic diseases in Blood and in the eye but trying to get gene therapy to the rest
1:57:37	of the body is still a challenge and so one of the things we're working on and having some successes being able to
1:57:44	deliver it to every cell in the body or nearly every cell in the body and not have it all concentrated in the liver
1:57:51	which is typically where these genes go when you deliver them IV But ultimately imagine a world let's be a little bit uh
1:57:58	uh of dreamers here if my colleagues will allow me imagine a world where you
1:58:04	you have these three genes put into your body let's say at 50 and then you're
1:58:10	basically like Deadpool if you get injured you can have an IV turn on these genes heal better you lose your eyesight
1:58:18	turn it on in the eye fix your eye who knows what have an idea whole body
1:58:23	Rejuvenation that would be pretty interesting and we've only reset aging once in the eye
1:58:29	we don't know if you can do it twice we don't know if you do it 10 times or infinitely
1:58:35	what more will be revealed we will come back I'll come back and tell you how things are going yeah please do we're
1:58:40	all counting on you you have the civilization rests on your shoulders the future of all of us
1:58:47	well and in the meantime the seat of your lab there's a lot we can do to stay healthy for longer and actually that
1:58:52	every year you're alive you get an extra three months of life because technology is changing that's encouraging that's
1:58:59	gonna that's gonna like allow us to end this on an optimistic note I think
1:59:04	um thank you super interesting um I really uh have so much respect for
1:59:09	the work that you're doing you did a beautiful job with this book um there's so much to learn and uh I
1:59:17	know that you're at The Cutting Edge of of learning it for all of us so come back and keep us up to date on
1:59:22	everything that's going on I'd love to yeah thank you so much um pick up the book lifespan support
1:59:27	local booksellers if you can't find it at your local Bookseller tell them to order it for you or uh go to Amazon
1:59:34	yeah right wherever good books are sold and uh David is easy to find on the internet it's just at David Sinclair PhD
1:59:42	on on Instagram on Instagram yeah Twitter is David uh a Sinclair cool
1:59:47	awesome man any anything else you want to let people know about before we end it here uh let's all celebrate uh 80 years from
1:59:54	now that sounds good man it's a plan
2:01:03	who's where's the party going to be your house I think we'll do it at your house all right good thank you man