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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 David Sinclair - ARDD2022 - Great release of unpublished data from David Sinclair's Lab: Difference between revisions

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2022-10-24 - Presentation Dr. David Sinclair - ARDD2022 - Great release of unpublished data from David Sinclair's Lab (view source)

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* https://www.youtube.com/watch?v=mfeu3nTuNbc&ab_channel=ARDD
* https://www.youtube.com/watch?v=mfeu3nTuNbc&ab_channel=ARDD
== Transcript ==
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| [Music]
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| foreign
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| [Music]
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| we are on to our final speaker who is on
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| Zoom
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| David we are ready for your talk
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| whenever you are ready to share your
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| slides all right let's do it hi everyone
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| wish I could be there wish I was there
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| uh next year for sure next oh that's
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| great
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| I'll hold you up to that promise I've
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| got my uh my father visiting from
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| Australia he's 83 and
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| I think that took precedent but uh next
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| year I'll bring him with me that would
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| be amazing that would be amazing okay
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| well thanks for inviting me let me get
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| my
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| presentation up and running
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| perfect great and I'll set a timer so
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| that we're good
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| okay all right so um yeah it's it's uh
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| it's amazing to be here this conference
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| to your credit uh and the other
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| organizers um just it's growing to be
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| one of the Premier conferences in the
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| world in this topic so hats off to you
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| and I've really enjoyed the the talks
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| uh so just because I don't have much
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| time I'll get straight into it
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| uh so I've been doing this for a while
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| started at MIT working in little yeast
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| cells and we discovered that and by we I
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| mean a lot of other people as well uh
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| the team discovered that uh their
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| reaction to genomic instability uh
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| particularly repetitive regions uh leads
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| to the reorganization of Chromatin which
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| leads to changes in gene expression and
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| phenotypes of aging and what we work on
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| in the lab is that that process that we
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| worked on in Lenny grunty's lab in yeast
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| in the mid-1990s uh is also true for
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| mammals um and that there's a backup
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| copy of information to reset the
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| epigenome
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| uh so what I'll do today is I'll share a
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| fair bit of unpublished research it's uh
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| it's really a coming out moment here
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| um so this is how we think in my lab
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| um similar to many others we like to
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| understand why we get old
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| uh and we think that the Hallmarks are
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| part of a whole system and we think that
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| the loss of information in particular is
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| is very important and information comes
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| in two types in in biology mainly it's
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| the DNA and the epigenome control
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| systems and we have a a lot of evidence
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| in the field increasingly so that the
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| epigenetic noise as we call it and the
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| loss of differentiation is a major
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| driver of of the process we call aging
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| and illness
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| 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
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| many organisms including humans to slow
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| down aging by targeting epigenetic
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| modifiers
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| um which include the sirtuins which we
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| worked on and continued to do so
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| I'm going to talk about the ability to
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| reverse aspects of Aging including
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| epigenetic age
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| and I'm going to talk about what we
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| really have talked about a lot at this
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| conference and in my lab we are
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:02
| fascinated with the
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| um the goal of having accurate clocks
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| that represent epigenetic aging if not
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| other aspects of Aging
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| 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
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| it does cover what we work on in my lab
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| this was from a review back in 2008 when
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| we published a paper that showed that
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| not just in yeast but in mammals
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| chromatin modifiers move around during
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| aging and that process can be
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| accelerated by extreme cellular damage
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| and what we used in this case was the
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| double-stranded DNA break or dsb and we
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| use an enzyme called people ppo1 to
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| accelerate what looked like aging and I
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| think you've heard probably me talk
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| about this before so I'll go quickly but
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| we've used this system to understand the
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| process of Aging in mammals and and how
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| to reverse it and just some some aspects
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| I want to point out
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| NAD is a cofactor co-substrate as you
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| know so Twins and we found that up
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| regulating cert one gene expression as
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| well as NAD levels in the cell can slow
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| down this reorganization of the
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| epigenome and prevent loss of gene
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| expression patterns and we did this in a
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| mouse back in 2008 in in neurons in the
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| brain but we've gone a long way since
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| then
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| come a long way oh we also I want to
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| report a little bit about mib626 which
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| is an NAD
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| precursor uh it's a polymorph of
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| nicotinamide mononucleotide that is GMP
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| pure it's been in humans and I'll update
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| you on that and how that seems to work
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| and our goal there is to have a drug
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| that will treat
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| um not just aging but diseases of aging
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| and they're about I think right now
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| we've got five clinical trials up and
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| running and I'll share some results of
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| that
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| um so what about the clocks uh we have a
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| paper that's up online it's not yet
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| published this is work by Patrick
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| Griffin and Jen Lee in my lab two
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| students who came up with the idea that
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| you can greatly reduce the the cost of
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| sequencing by uh transposon tagging DNA
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| samples and we can pull 500 or more
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| people or dogs or mice and we've built
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| some and Patrick and Jenna built some
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| really accurate clocks for Mouse tissues
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| and in humans you can see down below
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| 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
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| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:31
| go follow up on this news
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| um these are hot off the press human
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| clocks from Patrick they're really great
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| they've got um
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| all the attributes that you'd want this
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| is from human blood we have brought in
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| over a thousand human samples from
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| people a variety of Ages and you can see
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| that the the uh our values are really
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| great and uh the uh midday of 3.5 uses
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| it's not bad for a first start uh and
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| this is again just half the presses uh
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| the mouse ones look really good too I
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| would also phenotypic age clocks which
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| 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
|-
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| 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
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| 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
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| 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]
|}
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