2022-10-24 - Presentation Dr. David Sinclair - ARDD2022 - Great release of unpublished data from David Sinclair's Lab: Difference between revisions
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{{YouTubeVideo | |||
| YouTubeID = https://www.youtube.com/watch?v=mfeu3nTuNbc&ab_channel=ARDD | |||
| Length = | |||
| Interviewee = Dr. David Sinclair | |||
| Interviewer = | |||
| Summary = | |||
}} | |||
== Transcript == | |||
{| style="padding-top: 1em;" | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:00 | |||
| [Music] | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:00 | |||
| foreign | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:03 | |||
| [Music] | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:06 | |||
| we are on to our final speaker who is on | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:09 | |||
| Zoom | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:10 | |||
| David we are ready for your talk | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:12 | |||
| whenever you are ready to share your | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:15 | |||
| slides all right let's do it hi everyone | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:17 | |||
| wish I could be there wish I was there | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:20 | |||
| uh next year for sure next oh that's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:23 | |||
| great | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:24 | |||
| I'll hold you up to that promise I've | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:26 | |||
| got my uh my father visiting from | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:28 | |||
| Australia he's 83 and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:31 | |||
| I think that took precedent but uh next | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:33 | |||
| year I'll bring him with me that would | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:35 | |||
| be amazing that would be amazing okay | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:37 | |||
| well thanks for inviting me let me get | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:39 | |||
| my | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:40 | |||
| presentation up and running | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:43 | |||
| perfect great and I'll set a timer so | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:47 | |||
| that we're good | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:49 | |||
| okay all right so um yeah it's it's uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:52 | |||
| it's amazing to be here this conference | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:54 | |||
| to your credit uh and the other | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:56 | |||
| organizers um just it's growing to be | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:59 | |||
| one of the Premier conferences in the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:02 | |||
| world in this topic so hats off to you | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:04 | |||
| and I've really enjoyed the the talks | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07 | |||
| uh so just because I don't have much | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:08 | |||
| time I'll get straight into it | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:10 | |||
| uh so I've been doing this for a while | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:12 | |||
| started at MIT working in little yeast | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:14 | |||
| cells and we discovered that and by we I | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:16 | |||
| mean a lot of other people as well uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:18 | |||
| the team discovered that uh their | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:21 | |||
| reaction to genomic instability uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:24 | |||
| particularly repetitive regions uh leads | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:26 | |||
| to the reorganization of Chromatin which | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:28 | |||
| leads to changes in gene expression and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:30 | |||
| phenotypes of aging and what we work on | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:33 | |||
| in the lab is that that process that we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:36 | |||
| worked on in Lenny grunty's lab in yeast | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:38 | |||
| in the mid-1990s uh is also true for | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:41 | |||
| mammals um and that there's a backup | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:44 | |||
| copy of information to reset the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:46 | |||
| epigenome | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:48 | |||
| uh so what I'll do today is I'll share a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:50 | |||
| fair bit of unpublished research it's uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:53 | |||
| it's really a coming out moment here | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:55 | |||
| um so this is how we think in my lab | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:57 | |||
| um similar to many others we like to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:59 | |||
| understand why we get old | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:01 | |||
| uh and we think that the Hallmarks are | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:04 | |||
| part of a whole system and we think that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:06 | |||
| the loss of information in particular is | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:09 | |||
| is very important and information comes | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:12 | |||
| in two types in in biology mainly it's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:14 | |||
| the DNA and the epigenome control | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:16 | |||
| systems and we have a a lot of evidence | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:20 | |||
| in the field increasingly so that the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:22 | |||
| epigenetic noise as we call it and the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:25 | |||
| loss of differentiation is a major | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:28 | |||
| driver of of the process we call aging | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:31 | |||
| and illness | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:33 | |||
| um so I'm going to talk about efforts in | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:36 | |||
| many organisms including humans to slow | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:39 | |||
| down aging by targeting epigenetic | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:42 | |||
| modifiers | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:43 | |||
| um which include the sirtuins which we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:47 | |||
| worked on and continued to do so | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:50 | |||
| I'm going to talk about the ability to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:52 | |||
| reverse aspects of Aging including | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:55 | |||
| epigenetic age | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:57 | |||
| and I'm going to talk about what we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:58 | |||
| really have talked about a lot at this | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:00 | |||
| conference and in my lab we are | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:02 | |||
| fascinated with the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:04 | |||
| um the goal of having accurate clocks | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:07 | |||
| that represent epigenetic aging if not | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:10 | |||
| other aspects of Aging | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:12 | |||
| um it's a bit of a complicated slide but | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:14 | |||
| it does cover what we work on in my lab | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:17 | |||
| this was from a review back in 2008 when | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:20 | |||
| we published a paper that showed that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:23 | |||
| not just in yeast but in mammals | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:24 | |||
| chromatin modifiers move around during | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:26 | |||
| aging and that process can be | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:28 | |||
| accelerated by extreme cellular damage | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:31 | |||
| and what we used in this case was the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:33 | |||
| double-stranded DNA break or dsb and we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:36 | |||
| use an enzyme called people ppo1 to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:39 | |||
| accelerate what looked like aging and I | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:42 | |||
| think you've heard probably me talk | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:44 | |||
| about this before so I'll go quickly but | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:46 | |||
| we've used this system to understand the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:49 | |||
| process of Aging in mammals and and how | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:52 | |||
| to reverse it and just some some aspects | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:55 | |||
| I want to point out | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:56 | |||
| NAD is a cofactor co-substrate as you | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:59 | |||
| know so Twins and we found that up | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:03 | |||
| regulating cert one gene expression as | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:05 | |||
| well as NAD levels in the cell can slow | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:08 | |||
| down this reorganization of the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:10 | |||
| epigenome and prevent loss of gene | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:13 | |||
| expression patterns and we did this in a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:15 | |||
| mouse back in 2008 in in neurons in the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:18 | |||
| brain but we've gone a long way since | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:20 | |||
| then | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:21 | |||
| come a long way oh we also I want to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:24 | |||
| report a little bit about mib626 which | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:26 | |||
| is an NAD | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:27 | |||
| precursor uh it's a polymorph of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:30 | |||
| nicotinamide mononucleotide that is GMP | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:35 | |||
| pure it's been in humans and I'll update | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:37 | |||
| you on that and how that seems to work | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:39 | |||
| and our goal there is to have a drug | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:42 | |||
| that will treat | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:44 | |||
| um not just aging but diseases of aging | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:47 | |||
| and they're about I think right now | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:49 | |||
| we've got five clinical trials up and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:52 | |||
| running and I'll share some results of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:54 | |||
| that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:55 | |||
| um so what about the clocks uh we have a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:58 | |||
| paper that's up online it's not yet | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:00 | |||
| published this is work by Patrick | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:02 | |||
| Griffin and Jen Lee in my lab two | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:04 | |||
| students who came up with the idea that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:07 | |||
| you can greatly reduce the the cost of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:10 | |||
| sequencing by uh transposon tagging DNA | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:14 | |||
| samples and we can pull 500 or more | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:17 | |||
| people or dogs or mice and we've built | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:21 | |||
| some and Patrick and Jenna built some | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:23 | |||
| really accurate clocks for Mouse tissues | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:26 | |||
| and in humans you can see down below | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:28 | |||
| wherever I can I give you directions to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:31 | |||
| go follow up on this news | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:34 | |||
| um these are hot off the press human | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:36 | |||
| clocks from Patrick they're really great | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:38 | |||
| they've got um | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:40 | |||
| all the attributes that you'd want this | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:42 | |||
| is from human blood we have brought in | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:44 | |||
| over a thousand human samples from | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:47 | |||
| people a variety of Ages and you can see | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:49 | |||
| that the the uh our values are really | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:52 | |||
| great and uh the uh midday of 3.5 uses | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:57 | |||
| it's not bad for a first start uh and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:59 | |||
| this is again just half the presses uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:01 | |||
| the mouse ones look really good too I | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:04 | |||
| would also phenotypic age clocks which | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:05 | |||
| we've published on if you're interested | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:07 | |||
| you could check that out | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:10 | |||
| uh how about slowing aging well we've | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:12 | |||
| worked on activators of sirtuins for a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:15 | |||
| long time Resveratrol was the one back | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:16 | |||
| 20 years ago we've developed some | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:19 | |||
| synthetic ones and some NAD precursors | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:21 | |||
| uh mib626 is as I mentioned an oral | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:25 | |||
| formulation of a polymorph of mh66 that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:28 | |||
| stabilized crystalline and it's gone | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:30 | |||
| through a lot of safety studies over the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:32 | |||
| last few years headed by this lab are | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:35 | |||
| shally basin's group at Brigham and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:37 | |||
| Women's Hospital and David Livingston | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:40 | |||
| runs the group at Metro biotech which is | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:42 | |||
| a massachusetts-based company that's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:44 | |||
| been making NAD precursors both | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:46 | |||
| synthetic and natural for the last | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:48 | |||
| decade | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:49 | |||
| uh and that and full disclosure this was | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:51 | |||
| spun out of my lab and others including | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:54 | |||
| Sheena Mai and Raj after | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:57 | |||
| uh how do you measure uh what the effect | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 6:59 | |||
| might be well one of the ways that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:01 | |||
| Shelley's lab did it was to look at | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:03 | |||
| endurance and strength uh within an MRI | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:07 | |||
| and so this is uh an example of the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:10 | |||
| machine that they built to insert the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:11 | |||
| patients into the machine and measure | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:14 | |||
| their endurance strength and things like | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:16 | |||
| uh ATP NAD oxygenation | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:20 | |||
| um and some of the data that hasn't | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:21 | |||
| probably been published yet but we're | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:22 | |||
| starting to talk about it and this is | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:24 | |||
| their group's data not mine uh is that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:27 | |||
| uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:27 | |||
| a number of things happen when you take | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:29 | |||
| uh 1 000 milligrams from roughly a month | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:33 | |||
| of this uh substance orally | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:37 | |||
| and you can see here an example of some | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:39 | |||
| of the data uh the repetitions the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:41 | |||
| failure of that leg exercise uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:44 | |||
| significantly greater after taking | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:45 | |||
| mib636 this is similar or at least | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:48 | |||
| reminiscent to the mouse data that we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:50 | |||
| published in 2018 on endurance in mice | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:53 | |||
| due to increased vascularization of the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 7:57 | |||
| action on endothelial cells | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:00 | |||
| um and others nice bit of data I would | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:03 | |||
| admit it was a surprise a nice surprise | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:05 | |||
| is that Shelley's group showed that um | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:08 | |||
| lipids and cholesterol uh went in the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:11 | |||
| right direction for improved Health uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:13 | |||
| as you can see here | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:16 | |||
| uh HDL was not affected which was also | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:18 | |||
| reassuring | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:21 | |||
| uh what about acceleration of Aging now | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:23 | |||
| we do this for two reasons one is to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:25 | |||
| understand why we age because if we can | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:27 | |||
| cause it then we have some idea that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:29 | |||
| we're on the right track but we also | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:31 | |||
| want to know if we can have a model of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:35 | |||
| Aging that's much quicker because | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:36 | |||
| typical longevity experiment takes way | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:38 | |||
| too long and in organoids organoids are | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:40 | |||
| way too young when you build an organide | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:42 | |||
| from a stem cell an ipsc they're age | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:45 | |||
| zero which is not that useful and so | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:48 | |||
| we've used this system which you may | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:50 | |||
| know about it's close to getting | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:52 | |||
| accepted we hope uh last last stages of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:56 | |||
| this uh 12-year Journey | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 8:59 | |||
| um actually I started this project with | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:00 | |||
| Philip oberdorf when I was 39 so I've | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:03 | |||
| aged a little uh this project is uh the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:06 | |||
| combination of 20 labs around the world | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:10 | |||
| to see if we can displace chromatin | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:13 | |||
| modifiers in a way that mimics aging and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:15 | |||
| we've done that and that's this work | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:17 | |||
| which we call the ice system and we have | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:19 | |||
| cell based systems and mouse systems to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:21 | |||
| do that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:22 | |||
| and we'll use it in a minute I'll show | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:24 | |||
| you later but we can drive aging | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:26 | |||
| forwards as far as we can tell | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:27 | |||
| epigenetically and the other Hallmarks | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:29 | |||
| of Aging accelerate as well for the most | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:32 | |||
| part | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:33 | |||
| the reversal this is a very hot topic as | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:36 | |||
| you all know we use uh typically we use | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:40 | |||
| a combination of three of the yamanaka | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:42 | |||
| factors rather than four we leave out | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:44 | |||
| cmic and we're using other methods | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:46 | |||
| chemicals now as well we published this | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:50 | |||
| um in 2020 so I'm not going to repeat | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:53 | |||
| that data but we did use it to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:55 | |||
| rejuvenate neurons in mice and restore | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 9:57 | |||
| Vision in mice that had damaged or old | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:00 | |||
| retinas by targeting the neurons | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:03 | |||
| um and we find that we need all three of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:05 | |||
| those factors O S and K shown down here | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:08 | |||
| in this Vector that we can control with | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:10 | |||
| Doxycycline Teton and Ted off system if | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:12 | |||
| you would like to try it this isn't uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:15 | |||
| injections in the eye which was in the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:17 | |||
| the nature paper this one's the whole | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:19 | |||
| brain and we're using a variety of aavs | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:21 | |||
| now to infect different tissues and the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:23 | |||
| whole body in the in efforts to not just | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:26 | |||
| accelerate aging but take those mice and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:28 | |||
| wild type and reverse them and see what | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:30 | |||
| happens and this is work that I'm | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:32 | |||
| showing you from Xiao Tian uh primarily | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:36 | |||
| and jeun jeunyang and their goal is to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:39 | |||
| reverse the age of the brain and see | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:41 | |||
| what happens | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:42 | |||
| and uh well this was the paper I just | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:44 | |||
| wanted to remind you and we had a lot of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:47 | |||
| help from people in the field some of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:48 | |||
| who are at this conference uh Morgan's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:50 | |||
| here uh that in was great help Steve | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:53 | |||
| Horvath there's a long list you can see | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:55 | |||
| here I couldn't have done any of this | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:57 | |||
| without their Labs as well what was | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 10:59 | |||
| amazing about this was that we showed | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:01 | |||
| that there's a repository of youthful | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:04 | |||
| information that can reset a cell's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:06 | |||
| epigenome we measure gene expression on | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:08 | |||
| the right you can see it's nicely reset | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:10 | |||
| proportionally to how this genes were | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:12 | |||
| expressed when they were young this is | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:13 | |||
| RNA and on the left I think even | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:16 | |||
| just as impressive is the methylation | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:18 | |||
| patterns were largely restored as well | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:21 | |||
| um and the clock uh which uh Morgan and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:24 | |||
| Steve and that even helped us show uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:26 | |||
| was as well and one of the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:28 | |||
| interesting things in this paper is we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:29 | |||
| found that damage to neurons accelerates | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:33 | |||
| epigenetic aging as well so it's not | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:35 | |||
| just DNA cutting | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:37 | |||
| um or time it's extreme cell stress like | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:40 | |||
| a nerve Crush that can do it as well | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:43 | |||
| uh this has been commercialized or is | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:46 | |||
| being commercialized by life biosciences | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:48 | |||
| a boston-based company also spun out of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:50 | |||
| my lab you can check it out | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:53 | |||
| um and you'll probably get the website | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:54 | |||
| if you spell The Sciences correctly | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:57 | |||
| there's an e in there | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 11:59 | |||
| um Blackberry Sciences was started in | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:01 | |||
| 2017 uh Bruce Cassandra at Mass Eye and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:04 | |||
| Ear has done a lot of the pre-clinical | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:06 | |||
| work and safety work we've now got a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:08 | |||
| fair amount of data and we're now in | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:10 | |||
| non-human primates with a goal uh of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:12 | |||
| some time in uh the next whole to 24 | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:15 | |||
| months of uh starting uh work towards an | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:18 | |||
| IND and getting into humans if all goes | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:20 | |||
| well and our goal is to reverse | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:22 | |||
| blindness in a variety of different | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:24 | |||
| disorders in humans | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:26 | |||
| but it is remarkable if you reverse the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:28 | |||
| age of neurons in the retina you can | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:30 | |||
| restore vision and gene expression this | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:32 | |||
| way | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:33 | |||
| um of course I'm standing on the back of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:34 | |||
| some very big names uh in this field who | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:37 | |||
| uh showed pointed the way uh this is new | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:41 | |||
| data unpublished I was allowed to share | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:43 | |||
| this from Bruce Cassandra's lab | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:45 | |||
| uh he and I are infecting not the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:47 | |||
| neurons here but the retinal pigment and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:49 | |||
| pythelium cells rpe and these give rise | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:52 | |||
| to uh the photoreceptors and these | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:54 | |||
| degrade over time particularly in | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:56 | |||
| macular degeneration and what Bruce has | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 12:58 | |||
| found is that he can actually restore | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:00 | |||
| the morphology and the function of these | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:02 | |||
| cells and restore eyesight back to a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:04 | |||
| young State similar to what happens when | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:06 | |||
| you rejuvenate neurons in the eye as | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:08 | |||
| well | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:09 | |||
| the system uh in the lab now that we're | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:11 | |||
| doing is more human we have inducible | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:13 | |||
| human neurons uh where we can | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:16 | |||
| differentiate them both into flat | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:17 | |||
| cultures and three-dimensional and we do | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:20 | |||
| pro-aging with ice and reversal with osk | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:22 | |||
| typically okay I'll give you some | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:25 | |||
| examples of what we do | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:27 | |||
| and this is work mainly by Xiao and Jay | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:29 | |||
| in the lab we grow the nerves on these | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:31 | |||
| little culture dishes that can sense | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:33 | |||
| electrical signals uh when we have a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:35 | |||
| control induction of no osk there's not | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:40 | |||
| very good electrical firing but when we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:42 | |||
| rejuvenate them | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:44 | |||
| uh with uh the osk treatment uh just for | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:48 | |||
| a short amount of time this just takes a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:50 | |||
| little over a week we see that there's a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:54 | |||
| great induction of function | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:57 | |||
| um and it continues out the longer we go | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 13:59 | |||
| this is day 50 that you're seeing on the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:01 | |||
| right so that's just neurons that's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:03 | |||
| human neurons we've got Alzheimer's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:04 | |||
| patient neurons as well we can make | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:07 | |||
| these into little brain organoids you | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:09 | |||
| can see here that we can turn on all of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:11 | |||
| the three yamanaka factors that we like | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:13 | |||
| in these organoids which have a similar | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:15 | |||
| brain structure to ours great models | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:19 | |||
| um for human aging we can age these | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:21 | |||
| forward and get them to take on | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:23 | |||
| inflammatory and senescent signatures | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:26 | |||
| which I think will be a useful model | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:28 | |||
| in terms of reversal uh we've done this | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:30 | |||
| in mice as well we can now deliver the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:33 | |||
| osk system into various places in the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:37 | |||
| brain whole brain or in this case on the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:39 | |||
| right the excitatory neurons and in both | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:43 | |||
| cases we get an improvement in learning | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:45 | |||
| in these old mice which is what I think | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:49 | |||
| might have we might find out as a field | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:51 | |||
| is that diseases of old age particularly | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:53 | |||
| in the brain I'm thinking of like | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:55 | |||
| Alzheimer's if you make the the brain | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:57 | |||
| young then the diseases just go away | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 14:59 | |||
| because most of these diseases of Aging | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:01 | |||
| are caused by edging I mean it's obvious | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:03 | |||
| to a lot of us but to the rest of the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:05 | |||
| world it's not | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:07 | |||
| um so I want to thank the people who | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:09 | |||
| made this possible uh there's a large | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:11 | |||
| group The the clinical trial group is at | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:14 | |||
| Brigham and Women's Hospital there are | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:16 | |||
| four other clinical trials that are | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:18 | |||
| ongoing there's one actually for | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:20 | |||
| Alzheimer's disease that's starting to | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:21 | |||
| recruit there's one um well I won't say | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:25 | |||
| the whole lot but they're interesting | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:26 | |||
| ones | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:28 | |||
| um you can see that we've got | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:29 | |||
| collaborators both for exercise | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:31 | |||
| physiology the hormones and this is um | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:34 | |||
| the mib636 group at Metro biotech | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:38 | |||
| uh here we have uh the people in my lab | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:40 | |||
| that helped or did major contributions I | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:43 | |||
| want to point out the work of Jay who | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:45 | |||
| did the Ice Mouse | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:47 | |||
| um and matoshi I want to thank everyone | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:49 | |||
| really but I want to focus on I | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:52 | |||
| mentioned Xiao Jian | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:55 | |||
| um for the osk work uh Yuan Chang Liu | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 15:58 | |||
| who left the lab after he published | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:00 | |||
| rightly so uh he's uh not listed but he | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:03 | |||
| was the first author on that nature | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:05 | |||
| paper and I also want to point out Chris | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:07 | |||
| who's doing reversal of senescence uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:10 | |||
| Gerald who's working on a lot of the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:13 | |||
| mouse projects I could go on I won't uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:15 | |||
| do that but I do want to thank Patrick | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:17 | |||
| who I probably didn't mention enough he | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:19 | |||
| was the one that came up with this idea | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:21 | |||
| to do the time seek clock | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:23 | |||
| um so many collaborators it's impossible | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:25 | |||
| to thank everybody these are the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:26 | |||
| highlights and I am so grateful for | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:29 | |||
| their uh advice uh reagents and uh and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:32 | |||
| friendship over the years and the people | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:34 | |||
| who uh supported the work financially | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:36 | |||
| have been amazing too | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:38 | |||
| um so I'll stop there and take any | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:39 | |||
| questions thank you for having me | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:47 | |||
| thank you so much David we have a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:50 | |||
| question here in the front from one of | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:52 | |||
| our Inspire ambassadors | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:54 | |||
| they're the high school students that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 16:56 | |||
| are involved in the erdd organization | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:00 | |||
| hi my name is Andrea | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:02 | |||
| um I was just wondering so you you said | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:05 | |||
| that you used three of the Fourier | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:06 | |||
| Monica factors when looking at eyesight | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:09 | |||
| Rejuvenation have you tested any other | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:11 | |||
| combinations of these yamanaka factors | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:15 | |||
| we tested all combinations | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:18 | |||
| um and | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:19 | |||
| we needed three uh four uh worked as | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:23 | |||
| well but we were concerned about the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:26 | |||
| loss of cellular identity so we left c | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:28 | |||
| MC out and those three are necessary if | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:31 | |||
| we just do one or two combinations uh it | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:34 | |||
| did not work and if we gave them | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:36 | |||
| individually in different viruses it | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:39 | |||
| still didn't work so it seems like we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:40 | |||
| need to package them into the same AV | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:41 | |||
| three of them put them in a polycystron | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:44 | |||
| and get those in were there slight | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:46 | |||
| changes maybe but the the big difference | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:49 | |||
| was when when we put in all three now we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:52 | |||
| were trying for years different factors | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:53 | |||
| so we tried nanog and that didn't work | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:55 | |||
| very well it was pretty toxic | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 17:58 | |||
| um and I think I mean it sounds like we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:00 | |||
| just tried something and it worked but | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:01 | |||
| it was actually many years of one | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:03 | |||
| Chang's efforts to find this particular | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:05 | |||
| combination | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:08 | |||
| great thank you so much uh it's quite | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:11 | |||
| late here and we have we have a couple | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:13 | |||
| questions Paul sorry it's late for me I | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:15 | |||
| guess it's a couple of questions in the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:17 | |||
| back there | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:19 | |||
| hi I was wondering if you also tested | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:21 | |||
| the data that you showed in rpe cells in | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:24 | |||
| pathological conditions either genetic | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:26 | |||
| or chemical | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:29 | |||
| oh uh yeah so it's been done in a uh a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:32 | |||
| mouse model of macular degeneration | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:37 | |||
| um with the the iodide model if you're | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:39 | |||
| familiar with it and it uh it works well | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:42 | |||
| in that situation okay cool cool thanks | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:46 | |||
| there's another one from Lawrence | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:48 | |||
| hi David uh I don't know if you can see | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:50 | |||
| me it's Lauren Zion from vitadel I am | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:53 | |||
| wondering about the the time sake if you | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:55 | |||
| can talk a bit about the implications | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 18:57 | |||
| there uh how would it look like for the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:00 | |||
| consumer what does this enable what are | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:03 | |||
| the uh downsides as well | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:07 | |||
| uh yeah I don't know of any true | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:10 | |||
| downsides uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:12 | |||
| the cost is the main thing so what we do | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:14 | |||
| is we we barcode each each person's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:17 | |||
| sample and we run them through the same | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:19 | |||
| sequencing reaction there's also an | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:21 | |||
| enrichment step that I didn't mention uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:23 | |||
| and so it currently costs us | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:25 | |||
| less than a you know basically a few | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:27 | |||
| dollars less than five dollars per | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:29 | |||
| sample and that's just on the bench here | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:30 | |||
| not high throughput not optimized so we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:33 | |||
| think we can get the test down to really | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:35 | |||
| low amounts and for the consumer that's | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:37 | |||
| of course a benefit | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:40 | |||
| um it this technology is licensed to a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:42 | |||
| company that next year will if all goes | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:45 | |||
| well provide a product to Consumers | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:48 | |||
| um to try this out but I wouldn't | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:50 | |||
| release that until we've shown that it | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:52 | |||
| works well we've done I think a couple | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:53 | |||
| of thousand people so far we have 10 000 | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:56 | |||
| samples waiting to be tested and about | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 19:58 | |||
| 250 000 people on the waitlist so we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:01 | |||
| will use those numbers to aim to get a | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:03 | |||
| really good clock and not put it out | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:04 | |||
| there at all if it doesn't work I'm | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:07 | |||
| assuming the costs doesn't include the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:09 | |||
| the logistics right so it would only | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:10 | |||
| make sense in in batches with shipping | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:13 | |||
| or something like that | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:14 | |||
| yeah you know the shipping will be more | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:17 | |||
| expensive than the cost of the test | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:18 | |||
| eventually but yeah that that's just the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:21 | |||
| cost of the reagents and the the | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:23 | |||
| sequencing yeah | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:25 | |||
| great one more uh hello David uh so my | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:29 | |||
| question is have you ever tried to uh | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:31 | |||
| combine also fasting and color reduction | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:34 | |||
| as a synergistic effect in your | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:36 | |||
| reprogramming with the harmonica factors | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:38 | |||
| uh we have not we have not we | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:42 | |||
| have tried a few chemicals in | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:43 | |||
| combination and we're still working on | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:45 | |||
| that but no I think it's a good idea | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:48 | |||
| um | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:49 | |||
| it may be that some of the genes that I | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:52 | |||
| talked about today could be involved | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:54 | |||
| we'll try it | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:56 | |||
| thank you | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:57 | |||
| all right very cool thank you so much | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 20:59 | |||
| David that was a fantastic and inspiring | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:02 | |||
| talk we're looking forward | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:08 | |||
| and we're living we're looking forward | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:10 | |||
| to seeing you here next year so thank | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:13 | |||
| you so much and everybody will | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:16 | |||
| reconvene in 13 hours maybe we'll see | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:19 | |||
| each other in the bar thank you so much | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:21 | |||
| for today and see you later | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:29 | |||
| [Applause] | |||
|- | |||
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 21:33 | |||
| [Music] | |||
|} |
Latest revision as of 02:50, 15 September 2023
- Interviewee: Dr. David Sinclair
Transcript
0:00 | [Music] |
0:00 | foreign |
0:03 | [Music] |
0:06 | we are on to our final speaker who is on |
0:09 | Zoom |
0:10 | David we are ready for your talk |
0:12 | whenever you are ready to share your |
0:15 | slides all right let's do it hi everyone |
0:17 | wish I could be there wish I was there |
0:20 | uh next year for sure next oh that's |
0:23 | great |
0:24 | I'll hold you up to that promise I've |
0:26 | got my uh my father visiting from |
0:28 | Australia he's 83 and |
0:31 | I think that took precedent but uh next |
0:33 | year I'll bring him with me that would |
0:35 | be amazing that would be amazing okay |
0:37 | well thanks for inviting me let me get |
0:39 | my |
0:40 | presentation up and running |
0:43 | perfect great and I'll set a timer so |
0:47 | that we're good |
0:49 | okay all right so um yeah it's it's uh |
0:52 | it's amazing to be here this conference |
0:54 | to your credit uh and the other |
0:56 | organizers um just it's growing to be |
0:59 | one of the Premier conferences in the |
1:02 | world in this topic so hats off to you |
1:04 | and I've really enjoyed the the talks |
1:07 | uh so just because I don't have much |
1:08 | time I'll get straight into it |
1:10 | uh so I've been doing this for a while |
1:12 | started at MIT working in little yeast |
1:14 | cells and we discovered that and by we I |
1:16 | mean a lot of other people as well uh |
1:18 | the team discovered that uh their |
1:21 | reaction to genomic instability uh |
1:24 | particularly repetitive regions uh leads |
1:26 | to the reorganization of Chromatin which |
1:28 | leads to changes in gene expression and |
1:30 | phenotypes of aging and what we work on |
1:33 | in the lab is that that process that we |
1:36 | worked on in Lenny grunty's lab in yeast |
1:38 | in the mid-1990s uh is also true for |
1:41 | mammals um and that there's a backup |
1:44 | copy of information to reset the |
1:46 | epigenome |
1:48 | uh so what I'll do today is I'll share a |
1:50 | fair bit of unpublished research it's uh |
1:53 | it's really a coming out moment here |
1:55 | um so this is how we think in my lab |
1:57 | um similar to many others we like to |
1:59 | understand why we get old |
2:01 | uh and we think that the Hallmarks are |
2:04 | part of a whole system and we think that |
2:06 | the loss of information in particular is |
2:09 | is very important and information comes |
2:12 | in two types in in biology mainly it's |
2:14 | the DNA and the epigenome control |
2:16 | systems and we have a a lot of evidence |
2:20 | in the field increasingly so that the |
2:22 | epigenetic noise as we call it and the |
2:25 | loss of differentiation is a major |
2:28 | driver of of the process we call aging |
2:31 | and illness |
2:33 | um so I'm going to talk about efforts in |
2:36 | many organisms including humans to slow |
2:39 | down aging by targeting epigenetic |
2:42 | modifiers |
2:43 | um which include the sirtuins which we |
2:47 | worked on and continued to do so |
2:50 | I'm going to talk about the ability to |
2:52 | reverse aspects of Aging including |
2:55 | epigenetic age |
2:57 | and I'm going to talk about what we |
2:58 | really have talked about a lot at this |
3:00 | conference and in my lab we are |
3:02 | fascinated with the |
3:04 | um the goal of having accurate clocks |
3:07 | that represent epigenetic aging if not |
3:10 | other aspects of Aging |
3:12 | um it's a bit of a complicated slide but |
3:14 | it does cover what we work on in my lab |
3:17 | this was from a review back in 2008 when |
3:20 | we published a paper that showed that |
3:23 | not just in yeast but in mammals |
3:24 | chromatin modifiers move around during |
3:26 | aging and that process can be |
3:28 | accelerated by extreme cellular damage |
3:31 | and what we used in this case was the |
3:33 | double-stranded DNA break or dsb and we |
3:36 | use an enzyme called people ppo1 to |
3:39 | accelerate what looked like aging and I |
3:42 | think you've heard probably me talk |
3:44 | about this before so I'll go quickly but |
3:46 | we've used this system to understand the |
3:49 | process of Aging in mammals and and how |
3:52 | to reverse it and just some some aspects |
3:55 | I want to point out |
3:56 | NAD is a cofactor co-substrate as you |
3:59 | know so Twins and we found that up |
4:03 | regulating cert one gene expression as |
4:05 | well as NAD levels in the cell can slow |
4:08 | down this reorganization of the |
4:10 | epigenome and prevent loss of gene |
4:13 | expression patterns and we did this in a |
4:15 | mouse back in 2008 in in neurons in the |
4:18 | brain but we've gone a long way since |
4:20 | then |
4:21 | come a long way oh we also I want to |
4:24 | report a little bit about mib626 which |
4:26 | is an NAD |
4:27 | precursor uh it's a polymorph of |
4:30 | nicotinamide mononucleotide that is GMP |
4:35 | pure it's been in humans and I'll update |
4:37 | you on that and how that seems to work |
4:39 | and our goal there is to have a drug |
4:42 | that will treat |
4:44 | um not just aging but diseases of aging |
4:47 | and they're about I think right now |
4:49 | we've got five clinical trials up and |
4:52 | running and I'll share some results of |
4:54 | that |
4:55 | um so what about the clocks uh we have a |
4:58 | paper that's up online it's not yet |
5:00 | published this is work by Patrick |
5:02 | Griffin and Jen Lee in my lab two |
5:04 | students who came up with the idea that |
5:07 | you can greatly reduce the the cost of |
5:10 | sequencing by uh transposon tagging DNA |
5:14 | samples and we can pull 500 or more |
5:17 | people or dogs or mice and we've built |
5:21 | some and Patrick and Jenna built some |
5:23 | really accurate clocks for Mouse tissues |
5:26 | and in humans you can see down below |
5:28 | wherever I can I give you directions to |
5:31 | go follow up on this news |
5:34 | um these are hot off the press human |
5:36 | clocks from Patrick they're really great |
5:38 | they've got um |
5:40 | all the attributes that you'd want this |
5:42 | is from human blood we have brought in |
5:44 | over a thousand human samples from |
5:47 | people a variety of Ages and you can see |
5:49 | that the the uh our values are really |
5:52 | great and uh the uh midday of 3.5 uses |
5:57 | it's not bad for a first start uh and |
5:59 | this is again just half the presses uh |
6:01 | the mouse ones look really good too I |
6:04 | would also phenotypic age clocks which |
6:05 | we've published on if you're interested |
6:07 | you could check that out |
6:10 | uh how about slowing aging well we've |
6:12 | worked on activators of sirtuins for a |
6:15 | long time Resveratrol was the one back |
6:16 | 20 years ago we've developed some |
6:19 | synthetic ones and some NAD precursors |
6:21 | uh mib626 is as I mentioned an oral |
6:25 | formulation of a polymorph of mh66 that |
6:28 | stabilized crystalline and it's gone |
6:30 | through a lot of safety studies over the |
6:32 | last few years headed by this lab are |
6:35 | shally basin's group at Brigham and |
6:37 | Women's Hospital and David Livingston |
6:40 | runs the group at Metro biotech which is |
6:42 | a massachusetts-based company that's |
6:44 | been making NAD precursors both |
6:46 | synthetic and natural for the last |
6:48 | decade |
6:49 | uh and that and full disclosure this was |
6:51 | spun out of my lab and others including |
6:54 | Sheena Mai and Raj after |
6:57 | uh how do you measure uh what the effect |
6:59 | might be well one of the ways that |
7:01 | Shelley's lab did it was to look at |
7:03 | endurance and strength uh within an MRI |
7:07 | and so this is uh an example of the |
7:10 | machine that they built to insert the |
7:11 | patients into the machine and measure |
7:14 | their endurance strength and things like |
7:16 | uh ATP NAD oxygenation |
7:20 | um and some of the data that hasn't |
7:21 | probably been published yet but we're |
7:22 | starting to talk about it and this is |
7:24 | their group's data not mine uh is that |
7:27 | uh |
7:27 | a number of things happen when you take |
7:29 | uh 1 000 milligrams from roughly a month |
7:33 | of this uh substance orally |
7:37 | and you can see here an example of some |
7:39 | of the data uh the repetitions the |
7:41 | failure of that leg exercise uh |
7:44 | significantly greater after taking |
7:45 | mib636 this is similar or at least |
7:48 | reminiscent to the mouse data that we |
7:50 | published in 2018 on endurance in mice |
7:53 | due to increased vascularization of the |
7:57 | action on endothelial cells |
8:00 | um and others nice bit of data I would |
8:03 | admit it was a surprise a nice surprise |
8:05 | is that Shelley's group showed that um |
8:08 | lipids and cholesterol uh went in the |
8:11 | right direction for improved Health uh |
8:13 | as you can see here |
8:16 | uh HDL was not affected which was also |
8:18 | reassuring |
8:21 | uh what about acceleration of Aging now |
8:23 | we do this for two reasons one is to |
8:25 | understand why we age because if we can |
8:27 | cause it then we have some idea that |
8:29 | we're on the right track but we also |
8:31 | want to know if we can have a model of |
8:35 | Aging that's much quicker because |
8:36 | typical longevity experiment takes way |
8:38 | too long and in organoids organoids are |
8:40 | way too young when you build an organide |
8:42 | from a stem cell an ipsc they're age |
8:45 | zero which is not that useful and so |
8:48 | we've used this system which you may |
8:50 | know about it's close to getting |
8:52 | accepted we hope uh last last stages of |
8:56 | this uh 12-year Journey |
8:59 | um actually I started this project with |
9:00 | Philip oberdorf when I was 39 so I've |
9:03 | aged a little uh this project is uh the |
9:06 | combination of 20 labs around the world |
9:10 | to see if we can displace chromatin |
9:13 | modifiers in a way that mimics aging and |
9:15 | we've done that and that's this work |
9:17 | which we call the ice system and we have |
9:19 | cell based systems and mouse systems to |
9:21 | do that |
9:22 | and we'll use it in a minute I'll show |
9:24 | you later but we can drive aging |
9:26 | forwards as far as we can tell |
9:27 | epigenetically and the other Hallmarks |
9:29 | of Aging accelerate as well for the most |
9:32 | part |
9:33 | the reversal this is a very hot topic as |
9:36 | you all know we use uh typically we use |
9:40 | a combination of three of the yamanaka |
9:42 | factors rather than four we leave out |
9:44 | cmic and we're using other methods |
9:46 | chemicals now as well we published this |
9:50 | um in 2020 so I'm not going to repeat |
9:53 | that data but we did use it to |
9:55 | rejuvenate neurons in mice and restore |
9:57 | Vision in mice that had damaged or old |
10:00 | retinas by targeting the neurons |
10:03 | um and we find that we need all three of |
10:05 | those factors O S and K shown down here |
10:08 | in this Vector that we can control with |
10:10 | Doxycycline Teton and Ted off system if |
10:12 | you would like to try it this isn't uh |
10:15 | injections in the eye which was in the |
10:17 | the nature paper this one's the whole |
10:19 | brain and we're using a variety of aavs |
10:21 | now to infect different tissues and the |
10:23 | whole body in the in efforts to not just |
10:26 | accelerate aging but take those mice and |
10:28 | wild type and reverse them and see what |
10:30 | happens and this is work that I'm |
10:32 | showing you from Xiao Tian uh primarily |
10:36 | and jeun jeunyang and their goal is to |
10:39 | reverse the age of the brain and see |
10:41 | what happens |
10:42 | and uh well this was the paper I just |
10:44 | wanted to remind you and we had a lot of |
10:47 | help from people in the field some of |
10:48 | who are at this conference uh Morgan's |
10:50 | here uh that in was great help Steve |
10:53 | Horvath there's a long list you can see |
10:55 | here I couldn't have done any of this |
10:57 | without their Labs as well what was |
10:59 | amazing about this was that we showed |
11:01 | that there's a repository of youthful |
11:04 | information that can reset a cell's |
11:06 | epigenome we measure gene expression on |
11:08 | the right you can see it's nicely reset |
11:10 | proportionally to how this genes were |
11:12 | expressed when they were young this is |
11:13 | RNA and on the left I think even |
11:16 | just as impressive is the methylation |
11:18 | patterns were largely restored as well |
11:21 | um and the clock uh which uh Morgan and |
11:24 | Steve and that even helped us show uh |
11:26 | was as well and one of the |
11:28 | interesting things in this paper is we |
11:29 | found that damage to neurons accelerates |
11:33 | epigenetic aging as well so it's not |
11:35 | just DNA cutting |
11:37 | um or time it's extreme cell stress like |
11:40 | a nerve Crush that can do it as well |
11:43 | uh this has been commercialized or is |
11:46 | being commercialized by life biosciences |
11:48 | a boston-based company also spun out of |
11:50 | my lab you can check it out |
11:53 | um and you'll probably get the website |
11:54 | if you spell The Sciences correctly |
11:57 | there's an e in there |
11:59 | um Blackberry Sciences was started in |
12:01 | 2017 uh Bruce Cassandra at Mass Eye and |
12:04 | Ear has done a lot of the pre-clinical |
12:06 | work and safety work we've now got a |
12:08 | fair amount of data and we're now in |
12:10 | non-human primates with a goal uh of |
12:12 | some time in uh the next whole to 24 |
12:15 | months of uh starting uh work towards an |
12:18 | IND and getting into humans if all goes |
12:20 | well and our goal is to reverse |
12:22 | blindness in a variety of different |
12:24 | disorders in humans |
12:26 | but it is remarkable if you reverse the |
12:28 | age of neurons in the retina you can |
12:30 | restore vision and gene expression this |
12:32 | way |
12:33 | um of course I'm standing on the back of |
12:34 | some very big names uh in this field who |
12:37 | uh showed pointed the way uh this is new |
12:41 | data unpublished I was allowed to share |
12:43 | this from Bruce Cassandra's lab |
12:45 | uh he and I are infecting not the |
12:47 | neurons here but the retinal pigment and |
12:49 | pythelium cells rpe and these give rise |
12:52 | to uh the photoreceptors and these |
12:54 | degrade over time particularly in |
12:56 | macular degeneration and what Bruce has |
12:58 | found is that he can actually restore |
13:00 | the morphology and the function of these |
13:02 | cells and restore eyesight back to a |
13:04 | young State similar to what happens when |
13:06 | you rejuvenate neurons in the eye as |
13:08 | well |
13:09 | the system uh in the lab now that we're |
13:11 | doing is more human we have inducible |
13:13 | human neurons uh where we can |
13:16 | differentiate them both into flat |
13:17 | cultures and three-dimensional and we do |
13:20 | pro-aging with ice and reversal with osk |
13:22 | typically okay I'll give you some |
13:25 | examples of what we do |
13:27 | and this is work mainly by Xiao and Jay |
13:29 | in the lab we grow the nerves on these |
13:31 | little culture dishes that can sense |
13:33 | electrical signals uh when we have a |
13:35 | control induction of no osk there's not |
13:40 | very good electrical firing but when we |
13:42 | rejuvenate them |
13:44 | uh with uh the osk treatment uh just for |
13:48 | a short amount of time this just takes a |
13:50 | little over a week we see that there's a |
13:54 | great induction of function |
13:57 | um and it continues out the longer we go |
13:59 | this is day 50 that you're seeing on the |
14:01 | right so that's just neurons that's |
14:03 | human neurons we've got Alzheimer's |
14:04 | patient neurons as well we can make |
14:07 | these into little brain organoids you |
14:09 | can see here that we can turn on all of |
14:11 | the three yamanaka factors that we like |
14:13 | in these organoids which have a similar |
14:15 | brain structure to ours great models |
14:19 | um for human aging we can age these |
14:21 | forward and get them to take on |
14:23 | inflammatory and senescent signatures |
14:26 | which I think will be a useful model |
14:28 | in terms of reversal uh we've done this |
14:30 | in mice as well we can now deliver the |
14:33 | osk system into various places in the |
14:37 | brain whole brain or in this case on the |
14:39 | right the excitatory neurons and in both |
14:43 | cases we get an improvement in learning |
14:45 | in these old mice which is what I think |
14:49 | might have we might find out as a field |
14:51 | is that diseases of old age particularly |
14:53 | in the brain I'm thinking of like |
14:55 | Alzheimer's if you make the the brain |
14:57 | young then the diseases just go away |
14:59 | because most of these diseases of Aging |
15:01 | are caused by edging I mean it's obvious |
15:03 | to a lot of us but to the rest of the |
15:05 | world it's not |
15:07 | um so I want to thank the people who |
15:09 | made this possible uh there's a large |
15:11 | group The the clinical trial group is at |
15:14 | Brigham and Women's Hospital there are |
15:16 | four other clinical trials that are |
15:18 | ongoing there's one actually for |
15:20 | Alzheimer's disease that's starting to |
15:21 | recruit there's one um well I won't say |
15:25 | the whole lot but they're interesting |
15:26 | ones |
15:28 | um you can see that we've got |
15:29 | collaborators both for exercise |
15:31 | physiology the hormones and this is um |
15:34 | the mib636 group at Metro biotech |
15:38 | uh here we have uh the people in my lab |
15:40 | that helped or did major contributions I |
15:43 | want to point out the work of Jay who |
15:45 | did the Ice Mouse |
15:47 | um and matoshi I want to thank everyone |
15:49 | really but I want to focus on I |
15:52 | mentioned Xiao Jian |
15:55 | um for the osk work uh Yuan Chang Liu |
15:58 | who left the lab after he published |
16:00 | rightly so uh he's uh not listed but he |
16:03 | was the first author on that nature |
16:05 | paper and I also want to point out Chris |
16:07 | who's doing reversal of senescence uh |
16:10 | Gerald who's working on a lot of the |
16:13 | mouse projects I could go on I won't uh |
16:15 | do that but I do want to thank Patrick |
16:17 | who I probably didn't mention enough he |
16:19 | was the one that came up with this idea |
16:21 | to do the time seek clock |
16:23 | um so many collaborators it's impossible |
16:25 | to thank everybody these are the |
16:26 | highlights and I am so grateful for |
16:29 | their uh advice uh reagents and uh and |
16:32 | friendship over the years and the people |
16:34 | who uh supported the work financially |
16:36 | have been amazing too |
16:38 | um so I'll stop there and take any |
16:39 | questions thank you for having me |
16:47 | thank you so much David we have a |
16:50 | question here in the front from one of |
16:52 | our Inspire ambassadors |
16:54 | they're the high school students that |
16:56 | are involved in the erdd organization |
17:00 | hi my name is Andrea |
17:02 | um I was just wondering so you you said |
17:05 | that you used three of the Fourier |
17:06 | Monica factors when looking at eyesight |
17:09 | Rejuvenation have you tested any other |
17:11 | combinations of these yamanaka factors |
17:15 | we tested all combinations |
17:18 | um and |
17:19 | we needed three uh four uh worked as |
17:23 | well but we were concerned about the |
17:26 | loss of cellular identity so we left c |
17:28 | MC out and those three are necessary if |
17:31 | we just do one or two combinations uh it |
17:34 | did not work and if we gave them |
17:36 | individually in different viruses it |
17:39 | still didn't work so it seems like we |
17:40 | need to package them into the same AV |
17:41 | three of them put them in a polycystron |
17:44 | and get those in were there slight |
17:46 | changes maybe but the the big difference |
17:49 | was when when we put in all three now we |
17:52 | were trying for years different factors |
17:53 | so we tried nanog and that didn't work |
17:55 | very well it was pretty toxic |
17:58 | um and I think I mean it sounds like we |
18:00 | just tried something and it worked but |
18:01 | it was actually many years of one |
18:03 | Chang's efforts to find this particular |
18:05 | combination |
18:08 | great thank you so much uh it's quite |
18:11 | late here and we have we have a couple |
18:13 | questions Paul sorry it's late for me I |
18:15 | guess it's a couple of questions in the |
18:17 | back there |
18:19 | hi I was wondering if you also tested |
18:21 | the data that you showed in rpe cells in |
18:24 | pathological conditions either genetic |
18:26 | or chemical |
18:29 | oh uh yeah so it's been done in a uh a |
18:32 | mouse model of macular degeneration |
18:37 | um with the the iodide model if you're |
18:39 | familiar with it and it uh it works well |
18:42 | in that situation okay cool cool thanks |
18:46 | there's another one from Lawrence |
18:48 | hi David uh I don't know if you can see |
18:50 | me it's Lauren Zion from vitadel I am |
18:53 | wondering about the the time sake if you |
18:55 | can talk a bit about the implications |
18:57 | there uh how would it look like for the |
19:00 | consumer what does this enable what are |
19:03 | the uh downsides as well |
19:07 | uh yeah I don't know of any true |
19:10 | downsides uh |
19:12 | the cost is the main thing so what we do |
19:14 | is we we barcode each each person's |
19:17 | sample and we run them through the same |
19:19 | sequencing reaction there's also an |
19:21 | enrichment step that I didn't mention uh |
19:23 | and so it currently costs us |
19:25 | less than a you know basically a few |
19:27 | dollars less than five dollars per |
19:29 | sample and that's just on the bench here |
19:30 | not high throughput not optimized so we |
19:33 | think we can get the test down to really |
19:35 | low amounts and for the consumer that's |
19:37 | of course a benefit |
19:40 | um it this technology is licensed to a |
19:42 | company that next year will if all goes |
19:45 | well provide a product to Consumers |
19:48 | um to try this out but I wouldn't |
19:50 | release that until we've shown that it |
19:52 | works well we've done I think a couple |
19:53 | of thousand people so far we have 10 000 |
19:56 | samples waiting to be tested and about |
19:58 | 250 000 people on the waitlist so we |
20:01 | will use those numbers to aim to get a |
20:03 | really good clock and not put it out |
20:04 | there at all if it doesn't work I'm |
20:07 | assuming the costs doesn't include the |
20:09 | the logistics right so it would only |
20:10 | make sense in in batches with shipping |
20:13 | or something like that |
20:14 | yeah you know the shipping will be more |
20:17 | expensive than the cost of the test |
20:18 | eventually but yeah that that's just the |
20:21 | cost of the reagents and the the |
20:23 | sequencing yeah |
20:25 | great one more uh hello David uh so my |
20:29 | question is have you ever tried to uh |
20:31 | combine also fasting and color reduction |
20:34 | as a synergistic effect in your |
20:36 | reprogramming with the harmonica factors |
20:38 | uh we have not we have not we |
20:42 | have tried a few chemicals in |
20:43 | combination and we're still working on |
20:45 | that but no I think it's a good idea |
20:48 | um |
20:49 | it may be that some of the genes that I |
20:52 | talked about today could be involved |
20:54 | we'll try it |
20:56 | thank you |
20:57 | all right very cool thank you so much |
20:59 | David that was a fantastic and inspiring |
21:02 | talk we're looking forward |
21:08 | and we're living we're looking forward |
21:10 | to seeing you here next year so thank |
21:13 | you so much and everybody will |
21:16 | reconvene in 13 hours maybe we'll see |
21:19 | each other in the bar thank you so much |
21:21 | for today and see you later |
21:29 | [Applause] |
21:33 | [Music] |