WEBVTT

NOTE duration: "00:04:52.166"


NOTE Confidence: 0.98195267

00:00:04.720 --> 00:00:06.339
It has become very clear

NOTE Confidence: 0.98195267

00:00:06.559 --> 00:00:08.480
that aging is not just

NOTE Confidence: 0.98195267

00:00:08.480 --> 00:00:10.000
fait accompli. Aging is a

NOTE Confidence: 0.98195267

00:00:10.000 --> 00:00:11.059
malleable process.

NOTE Confidence: 0.9971924

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And it turns out that

NOTE Confidence: 0.9971924

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almost every intervention

NOTE Confidence: 0.97075737

00:00:16.395 --> 00:00:18.495
that extends lifespan and reduces

NOTE Confidence: 0.97075737

00:00:18.635 --> 00:00:20.095
disease burden in animals

NOTE Confidence: 0.9763794

00:00:20.635 --> 00:00:22.255
is a metabolic intervention.

NOTE Confidence: 0.99035645

00:00:22.954 --> 00:00:24.095
But there are also

NOTE Confidence: 0.99902344

00:00:24.475 --> 00:00:24.975
molecular

NOTE Confidence: 0.99902344

00:00:25.515 --> 00:00:26.015
pathways

NOTE Confidence: 0.9975586

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and sensors

NOTE Confidence: 0.9920044

00:00:27.994 --> 00:00:29.460
in the body that sense

NOTE Confidence: 0.9920044

00:00:29.699 --> 00:00:31.460
the energy that is available

NOTE Confidence: 0.9920044

00:00:31.460 --> 00:00:32.120
to cells.

NOTE Confidence: 0.9972168

00:00:32.500 --> 00:00:33.879
And if those are targeted,

NOTE Confidence: 0.95166016

00:00:34.180 --> 00:00:35.399
that extends lifespan.

NOTE Confidence: 0.9958191

00:00:36.100 --> 00:00:37.699
And when that happens, one

NOTE Confidence: 0.9958191

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of the things that's really

NOTE Confidence: 0.9958191

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exciting is that the immune

NOTE Confidence: 0.9958191

00:00:40.180 --> 00:00:40.680
system,

NOTE Confidence: 0.98856026

00:00:41.059 --> 00:00:43.300
which basically resides also in

NOTE Confidence: 0.98856026

00:00:43.300 --> 00:00:44.360
every organ,

NOTE Confidence: 0.9995117

00:00:45.335 --> 00:00:46.235
is rewired

NOTE Confidence: 0.96636355

00:00:46.775 --> 00:00:48.775
to have greater ability to

NOTE Confidence: 0.96636355

00:00:48.775 --> 00:00:50.635
repair the damage that occurs

NOTE Confidence: 0.96636355

00:00:50.775 --> 00:00:52.875
with age. So immuno metabolism

NOTE Confidence: 0.96636355

00:00:53.015 --> 00:00:54.695
or this interaction between these

NOTE Confidence: 0.96636355

00:00:54.695 --> 00:00:56.455
two systems, we think, has

NOTE Confidence: 0.96636355

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a lot of potential in

NOTE Confidence: 0.96636355

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terms of understanding the basic

NOTE Confidence: 0.96636355

00:00:58.935 --> 00:01:00.600
biology of the aging process.

NOTE Confidence: 0.9470215

00:01:04.200 --> 00:01:05.400
So we are interested in

NOTE Confidence: 0.9470215

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these two phenomenas where

NOTE Confidence: 0.95356333

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the thymus, this organ that

NOTE Confidence: 0.95356333

00:01:09.640 --> 00:01:11.319
produces protective t cells in

NOTE Confidence: 0.95356333

00:01:11.319 --> 00:01:13.159
the body that controls infections,

NOTE Confidence: 0.95356333

00:01:13.159 --> 00:01:14.095
but we also know it

NOTE Confidence: 0.95356333

00:01:14.095 --> 00:01:15.075
controls cancers.

NOTE Confidence: 0.9649251

00:01:15.935 --> 00:01:17.295
What happens is that this

NOTE Confidence: 0.9649251

00:01:17.295 --> 00:01:18.755
organ ages so fast.

NOTE Confidence: 0.9843084

00:01:19.055 --> 00:01:20.175
By the age of forty

NOTE Confidence: 0.9843084

00:01:20.175 --> 00:01:21.935
five, in a healthy human

NOTE Confidence: 0.9843084

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being,

NOTE Confidence: 0.99934894

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almost eighty five percent of

NOTE Confidence: 0.99934894

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the human thymus

NOTE Confidence: 0.989417

00:01:26.450 --> 00:01:27.670
is made up of fat.

NOTE Confidence: 0.989417

00:01:27.969 --> 00:01:28.850
So it's an organ that's

NOTE Confidence: 0.989417

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supposed to produce immune cells,

NOTE Confidence: 0.989417

00:01:30.049 --> 00:01:30.930
but it has now fat

NOTE Confidence: 0.989417

00:01:30.930 --> 00:01:31.829
cells in it.

NOTE Confidence: 0.9913018

00:01:32.209 --> 00:01:33.569
And the other end of

NOTE Confidence: 0.9913018

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the spectrum is the fat

NOTE Confidence: 0.9913018

00:01:35.490 --> 00:01:37.970
itself. The adipose tissue expands

NOTE Confidence: 0.9913018

00:01:37.970 --> 00:01:39.295
with age. Even if you

NOTE Confidence: 0.9913018

00:01:39.295 --> 00:01:41.134
maintain your normal body mass

NOTE Confidence: 0.9913018

00:01:41.134 --> 00:01:42.575
index, the fat that increases

NOTE Confidence: 0.9913018

00:01:42.575 --> 00:01:43.774
is called the visceral fat,

NOTE Confidence: 0.9913018

00:01:43.774 --> 00:01:44.975
the fat that lines our

NOTE Confidence: 0.9913018

00:01:44.975 --> 00:01:46.274
organs, internal organs.

NOTE Confidence: 0.9367879

00:01:47.854 --> 00:01:49.534
And what happens, very unique

NOTE Confidence: 0.9367879

00:01:49.534 --> 00:01:50.975
in this situation with aging,

NOTE Confidence: 0.9367879

00:01:50.975 --> 00:01:51.540
is that

NOTE Confidence: 0.99594724

00:01:52.020 --> 00:01:53.800
as that fat is expanding,

NOTE Confidence: 0.9962269

00:01:54.340 --> 00:01:55.700
the things that expand inside

NOTE Confidence: 0.9962269

00:01:55.700 --> 00:01:57.060
the fat are the immune

NOTE Confidence: 0.9962269

00:01:57.060 --> 00:01:57.560
cells.

NOTE Confidence: 0.9342288

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So on the other hand,

NOTE Confidence: 0.9342288

00:01:59.460 --> 00:02:01.140
you have thymus where it's

NOTE Confidence: 0.9342288

00:02:01.140 --> 00:02:02.180
supposed to produce the immune

NOTE Confidence: 0.9342288

00:02:02.180 --> 00:02:03.140
cells. It has now fat

NOTE Confidence: 0.9342288

00:02:03.140 --> 00:02:04.580
cells expanding in it. And

NOTE Confidence: 0.9342288

00:02:04.580 --> 00:02:05.655
then you have an adipose

NOTE Confidence: 0.9342288

00:02:05.655 --> 00:02:07.095
tissue whose whole purpose is

NOTE Confidence: 0.9342288

00:02:07.095 --> 00:02:08.235
to control metabolism,

NOTE Confidence: 0.9647042

00:02:08.695 --> 00:02:10.135
has now this excessive immune

NOTE Confidence: 0.9647042

00:02:10.135 --> 00:02:10.875
cell infiltration.

NOTE Confidence: 0.9626116

00:02:11.575 --> 00:02:13.435
And what's now becoming clearer

NOTE Confidence: 0.9626116

00:02:13.495 --> 00:02:14.235
is that

NOTE Confidence: 0.9786784

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both these processes

NOTE Confidence: 0.9849609

00:02:16.135 --> 00:02:18.590
actually converge to produce inflammation,

NOTE Confidence: 0.9796753

00:02:19.130 --> 00:02:20.410
which is now one of

NOTE Confidence: 0.9796753

00:02:20.410 --> 00:02:22.270
the central features that controls

NOTE Confidence: 0.9796753

00:02:22.410 --> 00:02:24.570
degenerative changes that happen with

NOTE Confidence: 0.9796753

00:02:24.570 --> 00:02:25.070
age.

NOTE Confidence: 0.9841657

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What we're trying to do

NOTE Confidence: 0.9841657

00:02:30.570 --> 00:02:31.470
is to

NOTE Confidence: 0.99902344

00:02:32.724 --> 00:02:33.465
really understand

NOTE Confidence: 0.98514813

00:02:33.845 --> 00:02:35.364
what are the mechanisms that

NOTE Confidence: 0.98514813

00:02:35.364 --> 00:02:36.965
are now dormant in humans

NOTE Confidence: 0.98514813

00:02:36.965 --> 00:02:37.845
that are living in the

NOTE Confidence: 0.98514813

00:02:37.845 --> 00:02:39.685
modern world. Because when we

NOTE Confidence: 0.98514813

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hit these dormant pathways,

NOTE Confidence: 0.9523926

00:02:41.845 --> 00:02:43.364
it actually extends lifespan in

NOTE Confidence: 0.9523926

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animals.

NOTE Confidence: 0.9906982

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Calorie restriction is a very

NOTE Confidence: 0.9906982

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good example of it. Okay?

NOTE Confidence: 0.9906982

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If you reduce the amount

NOTE Confidence: 0.9906982

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of calories that you're consuming,

NOTE Confidence: 0.9857422

00:02:50.970 --> 00:02:52.830
now there are adaptive mechanisms

NOTE Confidence: 0.9312391

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that we never actually have

NOTE Confidence: 0.9312391

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to utilize in our modern

NOTE Confidence: 0.9312391

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life that are now upregulated.

NOTE Confidence: 0.9729004

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Okay? And we want to

NOTE Confidence: 0.9729004

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harness that.

NOTE Confidence: 0.96501607

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So we're very much interested

NOTE Confidence: 0.96501607

00:03:01.764 --> 00:03:03.044
in nature. So there is

NOTE Confidence: 0.96501607

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this species that lives in

NOTE Confidence: 0.96501607

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the desert in Middle East.

NOTE Confidence: 0.96501607

00:03:06.805 --> 00:03:08.084
It's very unique in the

NOTE Confidence: 0.96501607

00:03:08.084 --> 00:03:09.285
sense that it lives close

NOTE Confidence: 0.96501607

00:03:09.285 --> 00:03:10.905
to six times longer

NOTE Confidence: 0.9182129

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in the desert.

NOTE Confidence: 0.98349607

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And this species of golden

NOTE Confidence: 0.98349607

00:03:14.325 --> 00:03:16.610
spiny mouse is extremely resilient

NOTE Confidence: 0.97906494

00:03:17.230 --> 00:03:18.689
to age related decline.

NOTE Confidence: 0.9624721

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And we're trying to understand

NOTE Confidence: 0.9624721

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what is

NOTE Confidence: 0.99174803

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present in this species that

NOTE Confidence: 0.99174803

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is now dormant in us.

NOTE Confidence: 0.9265625

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So the hope obviously is

NOTE Confidence: 0.92414737

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that these mechanisms that we're

NOTE Confidence: 0.92414737

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trying to understand that become

NOTE Confidence: 0.92414737

00:03:34.255 --> 00:03:35.555
dysfunctional with age

NOTE Confidence: 0.9554913

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and identify which ones are

NOTE Confidence: 0.9554913

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actually the drivers of that

NOTE Confidence: 0.9554913

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process of aging

NOTE Confidence: 0.98772323

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versus the ones that are

NOTE Confidence: 0.98772323

00:03:42.015 --> 00:03:42.835
just passengers.

NOTE Confidence: 0.98346627

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And one of the things

NOTE Confidence: 0.98346627

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that we have discovered along

NOTE Confidence: 0.98346627

00:03:46.050 --> 00:03:47.650
with several of our colleagues,

NOTE Confidence: 0.98346627

00:03:47.890 --> 00:03:48.870
across the world

NOTE Confidence: 0.95377606

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is a sensor

NOTE Confidence: 0.99975586

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in the immune system

NOTE Confidence: 0.91522217

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which senses damage. The sensor

NOTE Confidence: 0.91522217

00:03:54.849 --> 00:03:55.989
is called as the NLRP

NOTE Confidence: 0.91522217

00:03:56.050 --> 00:03:56.870
three inflammasome.

NOTE Confidence: 0.920166

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It's a long, long, complicated

NOTE Confidence: 0.920166

00:03:59.155 --> 00:03:59.655
name.

NOTE Confidence: 0.99679905

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But it is now becoming

NOTE Confidence: 0.99679905

00:04:01.715 --> 00:04:02.855
more and more clear

NOTE Confidence: 0.9851074

00:04:03.555 --> 00:04:04.035
that,

NOTE Confidence: 0.9691732

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as people are doing, you

NOTE Confidence: 0.9691732

00:04:05.635 --> 00:04:07.235
know, the omic studies in

NOTE Confidence: 0.9691732

00:04:07.235 --> 00:04:08.935
humans and in animals across,

NOTE Confidence: 0.8880615

00:04:09.475 --> 00:04:10.295
time span,

NOTE Confidence: 0.88991004

00:04:10.720 --> 00:04:12.800
that this mechanism, NLRP three,

NOTE Confidence: 0.88991004

00:04:12.800 --> 00:04:13.780
gets upregulated

NOTE Confidence: 0.95713586

00:04:14.080 --> 00:04:15.360
with age, something that we

NOTE Confidence: 0.95713586

00:04:15.360 --> 00:04:16.560
had been studying for close

NOTE Confidence: 0.95713586

00:04:16.560 --> 00:04:17.779
to fifteen years now.

NOTE Confidence: 0.9921875

00:04:18.240 --> 00:04:19.779
And if you lower it,

NOTE Confidence: 0.9512329

00:04:21.120 --> 00:04:22.080
you can not only extend

NOTE Confidence: 0.9512329

00:04:22.080 --> 00:04:23.200
lifespan in the animals, you

NOTE Confidence: 0.9512329

00:04:23.200 --> 00:04:24.020
actually reduce

NOTE Confidence: 0.9946289

00:04:24.320 --> 00:04:25.460
the onset of diseases.

NOTE Confidence: 0.9420166

00:04:27.015 --> 00:04:28.135
And good news is it's

NOTE Confidence: 0.9420166

00:04:28.135 --> 00:04:29.595
actually imminently druggable.

NOTE Confidence: 0.8659668

00:04:30.775 --> 00:04:32.075
So the hope obviously

NOTE Confidence: 0.97602767

00:04:32.455 --> 00:04:33.975
is that these mechanisms that

NOTE Confidence: 0.97602767

00:04:33.975 --> 00:04:35.515
we and others are discovering

NOTE Confidence: 0.97602767

00:04:35.815 --> 00:04:37.255
are eventually targetable. And if

NOTE Confidence: 0.97602767

00:04:37.255 --> 00:04:38.775
they are targetable, then whether

NOTE Confidence: 0.97602767

00:04:38.775 --> 00:04:40.135
that actually improves the health

NOTE Confidence: 0.97602767

00:04:40.135 --> 00:04:41.100
of older adults.

NOTE Confidence: 0.9657593

00:04:41.740 --> 00:04:43.260
And, obviously, you know, this

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has huge implications

NOTE Confidence: 0.9806858

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for for all of us

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because aging affects everyone.