2022-02-11 - Interview Dr. David Sinclair - REVERSE AGING: What To Eat & When To Eat To INCREASE LONGEVITY

Length: 1:27:03 (advertisment for next episode starts at 57:09)
Interviewee: Dr. David Sinclair

Transcript

Intro

0:00	so sugar you're saying accelerates aging and restricting sugar actually helps increase longevity one of
0:06	the best predictors of your lifespan is your blood fasting blood sugar yeah if there was one thing i could tell people to do if there was nothing else is eat
0:12	less not to an extreme i think there's there's a lot of mental diseases where people are eating far too little but if
0:19	you're a regular person and know how to eat the right anorexic yeah yeah yeah um
0:25	you know in teenagers don't don't do this but anyone who's
0:30	through puberty uh knows how to eat the right foods a lot of plants uh
0:36	not a lot of carbohydrates in my view um get most of your protein from plants so occasional meat is fine but i try to
0:43	restrict my meat i know there are a lot of carnivores out there yeah joe rogan doesn't like it when i tell him that meat might be but you also don't eat
0:49	carbohydrates so people get confused carbohydrates can be good right so the right ones broccoli is a carbohydrate so is you

Carbohydrates

0:57	know a bagel and they're very different exactly right and and you know and you've spoken a lot about this so i
1:04	don't need to hammer it too much but the right carbohydrates for sure uh but yeah be hungry once in a while so that's
1:09	that's the first point so keep your blood sugar low if you can but not too low because you
1:15	need your energy you need to your brain needs glucose another thing i do is i um i exercise
1:22	now i'm always at a keyboard or on my phone so it's it's hard so i spend about four hours at the gym
1:28	uh on a sunday with my son which is does two things it's fantastic four hours yeah we'll have to make up for it
1:35	somehow i don't think it works like that you don't okay i'm probably wearing out
1:40	my body but i do a combination of weights uh and then some aerobic yeah some high impact
1:46	uh training intensity training and then i also do something else that's that i think is becoming more common which is um
1:54	so those are two uh what i call hormetic what you would call hormetic induces stresses small
2:00	stress yeah better exactly what doesn't kill you makes you live longer yeah that's why organic food has more
2:05	nutrients because the phytochemicals are there to protect it and then when you have the stress of being organic which
2:12	is harder to survive you actually make more nutrients right so that that was one of the theories that i put out
2:18	xenophomesis the idea you can get the messages from stress plants and get them
2:23	for our body yeah um so the other stresses which we know less about but there's enough data which i put have put
2:30	in the book that says this is probably real is uh sauna and cold stress oh my god i do that all

Sauna Cold Stress

2:36	every day really i have like a steam shower and i find a sauna and i have a big bathtub and i go hot and then go in
2:43	the ice bath fantastic ice bath it's like the best thing ever well it'll certainly wake you up and it makes you
2:49	feel good if nothing else but i've looked into the data i did a lot of research for the book and so the cold stress um it'll boost your brown fat
2:57	brown fat has a lot of mitochondria puts out a lot of good molecules so that's what you can cryotherapy is not nonsense
3:02	i don't think so yeah but you know there's not hasn't been long-term studies but it makes sense um anyway i'm
3:07	a harvard professor but there's not been long-term studies [Laughter]
3:12	uh you're tenured now you can say whatever you want i get slept on the wrist
3:18	but the the the what's interesting about it is that the the brown fat we didn't know it existed
3:24	in humans until fairly recently only a decade ago but it seems more you have the better and the best way to induce
3:30	brown fat is to be cold especially across your back there's a lot of it back there if you can induce it the problem is i found
3:36	that at least in animals the older you get the harder it is to build up so you want to start early in life if you can
3:43	and and build it up then the heat stress i looked into and i was really skeptical that any of this was real my my wife told me about saunas i
3:50	went come on that that can't be good for you but you look and actually there's a lot of studies in helsinki
3:55	of course yeah well they're selling the saunas so they they've done a lot of research thousands
4:01	of finnish men mostly have been studied and in in those studies it's pretty
4:06	clear that men who go to the sauna a few times a week have less cardiovascular disease risk and heart attacks now
4:13	there's one caveat which they actually admit in one of the papers is that people who are sick or in hospital don't
4:18	go to the sauna as often so there's that caveat but i looked at the data to me it looks like it could be real

resveratrol

4:25	so i do both and it does increase the uh resiliency of your cardiovascular
4:30	system when something called heart rate variability improves and heart failure patients do better when they actually go
4:35	in saunas yeah that's right so these are the stresses that i do on my body um i take
4:42	a gram of resveratrol in the morning with a tiny bit of homemade yogurt not not a lot of food but
4:47	uh i found that there's a type of yogurt that's that's really great um
4:53	for me at least like wine yogurt now with the refrigerator well i i don't know if if uh if you want me
5:00	to talk about actual products but uh there is one out there that i use and make it it's it's pretty tasty uh the
5:06	resveratrol dissolves in the yogurt that's the important part um if you just take a dry pelletive reservation most of
5:12	it won't be absorbed and that's the problem i take metformin a couple of them a gram
5:19	wow sometimes in the morning sometimes at night depending on how i feel i don't do well on metformin it's actually
5:24	pretty rough on my stomach so i don't really need it no not if you do the other things
5:30	yeah well probably probably i'm trying i'm trying to see on my body what works what doesn't it's
5:36	an experiment progress uh what else do i do so at night uh i take the usual things i take coq10
5:43	i take a statin you'll probably frown on that but i had very high cholesterol when i was a kid
5:49	uh i started on a stratin when i was 29 and my grandmother had a stroke when she was in her 30s so
5:54	i have really bad estrogen about the mitochondrial effects of statins i am um but i'm also worried about
6:01	really high cholesterol up in the high 200s oh yeah yeah so i had to do something
6:06	i'd like to go off the statin that would be probably the best thing i could try well there's experiments you can do where you can change your diet change
6:13	your lifestyle do different things stop it see where you do restart it check your particle size number i mean those
6:19	are all relevant right right i also have another bad gene on particle size so i'm not destined to live long enough so i do

alpha lipoic acid

6:24	something uh plant sterols i'm trying that to see if i can use those to replace the statins but coq10 is good
6:32	and i take um actually alpha lipoic acid yeah for mitochondria yeah
6:37	and one of the actually the thing that turned me on to that was uh i spoke to
6:42	denim harmon's family so denim harman you may know him he's the father of the oxidative stress theory of yeah and and
6:49	so he i i was fortunate to win an award with his name on it and i went out there
6:55	and his family were very generous to host me and he was still alive at the time he passed four a few years ago but
7:01	he was still healthy and going into work at 92 and so i said what is what's his secret oh lipoic acid
7:07	i thought well at the very least it didn't hurt him so again that i take it every day yeah it's it's if
7:12	you understand what it does it's basically one of the most powerful antioxidants that helps boost glutathione which is detoxifier it's
7:18	anti-inflammatory it helps your mitochondria it helps detoxify from metals it it sort of uh
7:24	helps with blood sugar and diabetics it helps with diabetic neuropathy i mean it's a really well studied molecule and
7:29	it's all about the mitochondria well yeah i would say that too the the other thing that i should point out is

monitor yourself

7:36	um so i monitor myself fairly regularly um i'm i'm not crazy about it i don't like having my blood drawn often but you
7:43	know i'm looking at myself with rings i've got the watch i've got the blood drawers if something goes out of whack
7:49	and i change my diet or i do something i'll know about it i measure through inside tracker others can do
7:55	that yeah about 34 different things and you know i'm i'm adding things i'm
8:00	subtracting them like you i know if something's going wrong so i just had a blood test because i'm going to africa
8:06	and uh i sat down with it with the nurse actually yesterday and she took me through my blood test yeah and she went
8:13	perfect perfect better than perfect better and so she said and you're turning 50 and you've got those blood markers
8:19	yeah she goes i'm jealous i said what do you think and she goes just keep doing what you're doing right right so i think
8:24	that's the proof that we're not hurting ourselves and we'll know it if we were yeah maybe long-term you don't know yeah
8:31	when we we see it all the time i see it you know treating patients where they're they're literally biology can reverse at
8:37	any time you know you see people who are in their 60s who have all these end stage diseases like heart failure and diabetes
8:44	and severe obesity and hypertension and kidney failure and you see these things go away when
8:49	you start to modify these factors that drive inflammation and blood sugar and mitochondria it's pretty amazing yeah

paradigm shifts

8:55	well there have been a few paradigm shifts in the field so when i started out and this is we're talking about the early 1990s
9:01	the idea was our bodies are like cars we eventually wear out there's not much you can do about it you can slow down the rusting
9:08	free radicals and that's about it but what we discovered in the 90s thanks to works by cynthia kenyon and lenny
9:13	guerinian and others is that these genes are tunes and there are some others we can talk about later
9:19	i think but these these protective pathways exist we didn't know that we had protective pathways it's as though we've
9:25	discovered the not just that our bodies are better than cars that we actually have
9:30	inbuilt repair systems yeah it's like it's so clean like a self-cleaning uh oven right yeah and they get they get
9:36	lazy if you if you're lazy they get lazy if you become obese and don't eat well and if you eat too much
9:42	um there are other things you can do to kick them into action with how you eat what you eat but also what we found is
9:49	that that you can they're basically inbuilt survival mechanisms that are very ancient they're found in yeast cells and plants in our bodies probably
9:56	our microbiome plays a role uh and that so we can we can basically make a call to the
10:02	to the pentagon of the body and they can send out the troops without actually damaging the body you don't have to have a war to get ready for war and these
10:10	protect us against diseases and many cases reverse aspects of aging another paradigm shift was that we could delete
10:16	the the bad cells in the body the senescent cells that accumulate and there are some molecules in
10:22	in clinical trials as well that might be paradigm shifting how do you delete those well they're called synalytics uh
10:28	senescent lytics lytic meaning lice the cells kill them yeah and there are molecules that can do that there are
10:34	some natural molecules quercetin corsetin from onions and apples
10:39	to satin nibs a drug on the market we well actually work at the mayo clinic
10:44	primarily and judy campesi out at the buck institute found that you can treat animals and delete their senescent cells
10:50	and they get younger so you basically like go in and like clean up all the bad cells yeah we call these the zombie
10:56	cells uh they they're half dead they sit there
11:01	they should be dead but they they're actually causing havoc they're they're secreting inflammation factors cytokines
11:07	that cause other cells to siness and to become um potentially cancerous
11:13	and when you delete them uh mice live longer and what's exciting about that technology
11:18	is you can instead of taking a pill every day which is the kind of stuff that i work on if their stuff works you can have a
11:24	treatment once every decade maybe and that's it and the treatment is a drug is it a
11:30	quercetin well you you can supplement there's nothing fully proven in humans yet uh there are some early
11:36	studies from the mayo clinic um just this year the study in humans came out that was promising from jim kirkland uh
11:44	but in mice a lot of studies now point to this being a phenomenal way to address aging so you have kind of
11:49	different pathways you can work on at the same time right you can work on the killing all the bad aging cells and you work on optimizing and revving up your
11:56	engines for like tuning up your engine well we're in a remarkable time for aging because we've moved from

we are in a remarkable time

12:02	just understanding what's causing it and how we might intervene to truly understanding
12:08	what can be done and now we're in a phase where the question is what are the right combinations of diet exercise
12:15	food supplements and eventually drugs that are on their way um and so i mentioned two paradigm
12:20	shifts there's a third one that maybe we can touch on later um and that's reprogramming cells and
12:26	with an understanding of actually what's controlling the clock of aging and how to wind it back because you said you

the clock of aging

12:31	know this limit of 100 years or 120 is not necessarily a hard stop that there there may be ways
12:38	of understanding the aging process that we can interrupt that well there are plenty of animals and
12:44	certainly species across the planet that live longer than we do it's not a biological
12:49	impossibility to live hundreds actually thousands of years there's even some corals that live for ten thousand
12:55	years so it's it's not a fact of life that we have to die at 120. uh if you remove predators and war and
13:02	disease species evolve longer life spans it's happening right now on a japanese island where a lizard was released and
13:08	it's got no predators it's breeding slower and living longer that's what happens and give us a few moments
13:14	doesn't it it doesn't actually just it sits there in the sun all day right well you know we we don't have
13:19	we we you know we don't have to necessarily live at the bottom of the ocean like a greenland shark or on a rock but what what these organisms show
13:26	us is that life lifespan is malleable it changes over millions of years sometimes
13:32	in the course of a few generations as we're seeing with this lizard what is happening that's what we i want
13:38	to figure out what is it about those organisms that we can learn from and instead of letting us evolve by having
13:43	to wait for us to evolve over millions of years why don't we just accelerate
13:48	gene editing or is this going to involve more of these other kinds i touch on gene editing in the book in my lab we're using gene therapy to
13:56	kind of leap frog and really see how powerful
14:01	our genome can be we're having some remarkable results in mice and truly reversing the clock of aging and seeing
14:07	what can happen and uh you know maybe maybe i'll tell i'll reveal that later okay it's fascinating
14:13	i i i have an apoe2 gene and a three which is two is like the
14:19	ones who can live forever drink smoke and not exercise and live to 120. and then the four is the bad one you get
14:25	alzheimer's so how do i like change my three out for a two can i do that i'm gonna get a double two it'll it'll be

gene therapy

14:31	possible where we're at with gene therapy is so there are a couple of drugs on the market that are used for rare diseases
14:37	because that's usually when new technologies are first used uh
14:42	you know there are scientists who could probably do this to themselves if they're crazy right now technology is there where we're not at the science
14:49	doesn't doesn't allow us to change every cell in the body right now even in a mouse where we've been
14:55	studying this longer and my lab does this every few weeks in in the lab the problem is we can infect
15:03	about 30 of the cells and it infects and changes the genes in some more organs
15:09	more than others yeah so it's very easy to change most cells in the liver yeah but not so much in the muscle in the
15:14	brain and you only get one or two shots at it because an adenovirus which is what carries the gene therapy
15:21	causes in an inflammatory response right that's not good uh so i you know i'm not i'm not
15:26	planning on doing that any time soon yeah uh but if i had a rare disease and i was gonna it was gonna kill me or i
15:32	was 95 and i had nothing else to lose maybe i'd consider it unbelievable so
15:38	the whole goal here isn't just to extend lifespan right it's to spend extend health span
15:44	right which is how long vibrant ears you have and uh there there's a lot of thinking that
15:50	if we extend lifespan there's going to be a lot of old people are going to be sick and cost the system money and drain this you know our society and that's not

survival curve

15:57	a great thing and yet there are others that sort of pointed to research that maybe that's not the case that if we
16:02	figure out how to create health then we can do what we call rectangularize the survival curve james
16:08	freeze wrote about this decades ago where we talked about how people who didn't smoke who exercised and kept the
16:13	normal body weight live longer and were healthier and just didn't get sick they just basically fell
16:19	off the cliff and died as opposed to long slow painful deaths they died quickly painlessly and cheaply yeah well
16:25	that's what the science is pointing to and in my lab we see that a lot when we intervene with a molecule uh we see
16:30	those mice that are healthier for longer and actually you know when i talk to people about living longer and i ask how long do
16:37	people want to live a typical answer is oh i wouldn't want to live over 100 because they people have seen what 100 year old looks like
16:43	it you know god forbid that we get there but what changes their minds is what if you could
16:49	be 100 and still play tennis and hang out with your great-grandkids and still be productive you don't have to be
16:56	earning a living you can be helping the community non-profit work and then everyone raises their hand pretty much so it's all about health
17:03	and that's the key point um i want everybody to know that i don't know how to extend lifespan without keeping
17:08	people healthy in fact the reason that's how you do it that's how we do it right that's the only way we can extend
17:14	lifespan is to keep animals and eventually people free of disease for longer and then eventually
17:19	something gives out fairly quickly typically and that's the idea someone like my father who's 80 now and still
17:25	traveling the world and going out every night and hanging out girlfriends 20 years younger well yeah multiple uh friends or girls i

healthcare costs

17:33	don't know if they're girlfriends but but that's a life that that i think is is well lived and if he can keep going
17:39	and helping my family and his community which he's doing for another 10 or 20 years the the
17:44	economics show and we've modeled this for australia we've done some others have done this for the uk gdp goes up
17:51	it's not that there's a drain at all in fact the the amount of healthcare at 17 of gdp right now in the us it's only
17:57	going to keep going up the reason is we're getting older and sicker the last 10 years of life can be spent
18:04	in in wheelchairs and not going outside and being spoon-fed i've seen that with my grandmother so my father's mother at
18:10	80 could barely walk she was in a wheelchair spent the last 10 13 years of
18:15	her life in a state that you wouldn't wish on your enemies and the expense to keep her alive was
18:22	ridiculous my father on the other hand he's contributing yeah you know what that's
18:27	that's what i talk about in the book is that the future is bright if we can tackle this problem keep people healthy
18:32	for longer the problem is if we don't succeed we we have an issue too the world's economy is
18:38	going to be dragged down by all the sick elderly people that are coming along it's true i just read a study the other
18:43	day that was a macroeconomic analysis of chronic disease just the united states the direct and indirect costs over 35
18:49	years it's 95 trillion dollars with a t that's over 3 trillion a year and if we figured out how to fix that
18:56	we literally have money for everything we need in this country infrastructure free education forgiveness of student loans free health care for everybody uh
19:04	yeah basic you know raising everybody out of poverty i mean it just would be a game changer right yeah you know you i

why work on aging

19:10	couldn't have said it better one of the things that that people challenge me on they say why work on aging don't we have more
19:16	important problems global warming species extinction i'm all for that i'm the biggest greeny and
19:22	and you know i was going to be an animal rights activist if it wasn't working on aging but i think the best way to tackle the
19:28	problems we have is actually first solve the biggest drain on the planet which is taking care of the sick and the elderly
19:33	yeah and then like you said there's trillions of dollars if we could uh just reduce one disease of aging by ten
19:39	percent it's about three trillion dollars over the next decade we're talking about a lot more than that and
19:45	that's money you can use to to fix the world and your thinking is actually the thinking that i think can solve the
19:50	problem because in medicine most of the thinking is focused on disease you're focused on the mechanisms of health
19:57	well i mean it's important to know why people die and we have a list of fourteen thousand diseases in yeah well
20:03	it's 155 000 yeah but but knowing why people fall off a cliff i would argue
20:10	it's also just as important if not more important to know what drove them to the cliff in the first place so it's fascinating you know one of the
20:15	things that we uh think about in terms of aging is it this it's this inevitable and external
20:22	process that goes in one direction and you're challenging that idea you're saying maybe what we see is aging isn't
20:27	actually healthy aging it's abnormal aging and then it it's really a based on a series

is aging healthy

20:33	of biological dysfunctions that we can understand and we can modify through either diet or lifestyle or
20:41	maybe nutri nutrients that we take or supplements right well um why why not first of all
20:47	just philosophically let's talk about that um is aging a condition well i believe it is i think you could argue
20:54	i make the argument in the book that disease is something that happens over time that's
20:59	deteriorates reduces function uh if it happens to less than 50 of the population if it happens to 51
21:06	we call that aging and it's arbitrary and the mere fact that it happens to most of us um if we live long enough and
21:13	if we're lucky enough doesn't mean it's any less important in fact i would argue it's more important
21:18	and so the one of the the things that i'm i'm very keen on explaining
21:23	to everybody is that that aging is something that we can tackle just as we've been tackling cancer and heart
21:29	disease and this inevitability uh cancer is inevitable if you live long enough so is heart disease so is dementia the
21:36	longer you live the more chance you'll get it okay but not inevitable well i would say every disease of aging
21:42	is inevitable as long as you live long enough right so you don't you have to die of something
21:47	you can't die of old age uh well something has to go wrong but what is the driver of all of those
21:53	diseases science says it's aging you if you're if you're a
21:59	teenager you don't get alzheimer's you don't get cancer and we don't often think why that is but the most important
22:04	factor by a factor of 100 or more is the aging process so if you can keep
22:10	the body younger and functioning like it did when we're in our 20s you're you're literally not going to get
22:16	heart disease you're not going to get alzheimer's yeah and as we learn more and more about how to reverse not just the effects of eating but
22:22	actual the age of cells themselves i believe we will be able to prevent in large part these diseases
22:29	because we've removed the largest cause of these diseases yeah i mean i think you know what you said is sort of implying that
22:36	there's common root causes of all these diseases we see with aging then if we
22:41	focus on those root causes that we can modify the trajectory of all those diseases and we don't have to
22:47	treat all of them independently right well i call it whack-a-mole medicine the way we do it now which is fine um you
22:53	know i think anybody who focuses on medicine and research um is doing a great service to to the world
23:00	i do think we can have a big impact if we can find out what's driving all those diseases and it's not intuitive unless
23:06	you're in the field that what's driving those diseases that we all see in our
23:11	families there's something common and actually in the book i have a theory that explains why
23:18	or what is the underlying cause of all the diseases that we get as we get older not just all diseases wrinkles yeah and
23:24	gray hair and all of that stuff it's all the same i believe it's all the same process that can not just be slowed down
23:29	but even reversed well this is such a radical shift in thinking in medicine right and in traditional medicine you've got your diseases and they're all
23:35	separate and dementia is different from heart disease different from diabetes from cancer different from you know all
23:41	these hypertension right they're all separate illnesses in in functional medicine we think about
23:46	the body as a system and it's having a few common root causes and a few key systems that when they function well
23:53	disease doesn't have a chance right so whether it's the mitochondria which you've been studying when you talk about
23:59	the powerhouse of the cell whether it's inflammation and your immune system or whether it's your microbiome or whether
24:04	it's your hormonal regulation these are all connected and and the key to solving the puzzle of disease and aging is
24:11	really understanding these common links right well that that's why i think we hit it off over a decade ago is that i'd
24:17	rarely met a doctor who talks like you do more and more are but uh it really it's
24:22	it's been missing and i teach medicine at harvard medical school uh for what that's worth and the way we
24:28	teach it is treat the symptom not treat the cause yeah yeah and it's in in so in aging it
24:35	seems like there's things that happen uh and and i want to get into why but we see increase in inflammation and aging
24:41	we see a decrease in mitochondrial function which are these energy cells so we lose energy basically our engine gets the carburetor gets full of whatever and
24:47	it doesn't work we see hormonal changes lower testosterone higher cortisol or growth hormone increased insulin
24:54	increased blood sugar we see changes in the microbiome that degrade over time we see changes in in our
25:00	ability to sort of metabolize things and toxins uh these are all these are all things that we can understand now with
25:06	the science we have which we couldn't even a few decades ago it's it's what we've been doing in functional medicine without really understanding that much
25:12	of the science because it's all emerging but your work has really started out with looking at the mitochondria as a

Mitochondria and aging

25:18	key to aging and that has sort of led you to some of these other linkages right well mitochondria i didn't set out
25:25	to study mitochondria it's our research pointed in that direction that they were part of the puzzle we started out when i
25:31	was with leona guerini you mentioned my former mentor and still friend uh we we started out
25:37	the question why do organisms grow old in the first place simple question very few people had actually
25:42	asked it and uh so we studied yeast cells from you know bakers and brewers use it all
25:48	the time why do ye cells not live forever and they typically live a week we actually found out that these
25:53	genes that you mentioned sirtuins are regulators of yeast aging and we have seven of these genes in our bodies and
25:59	they do phenomenal things they repair dna help teal a mist
26:04	and one of the things we found they do very well is keep the mitochondria healthy and actually we found what was
26:11	surprising was how reversible the aging of mitochondria are in animals at least and we're now doing human studies in
26:17	clinical trials that within just a week of treatment with a molecule that a few molecules that we've tested that
26:23	enhance the function of certains resveratrol was a famous one we we worked on now nad
26:29	boosters all seem to be able to reverse mitochondrial dysfunction within days and we never
26:36	knew that aging was that malleable until then yeah so so let's get down and deep a
26:41	little bit so the the thing you're working on now is is similar to what you're working on around
26:47	resveratrol which is the active ingredient in red wine um except
26:52	you know the equivalent amount of dose you use i think was like 1500 bottles of red wine so it's not something here
26:57	people should try at home but you you've because that worked on certains would work on mitochondria but now you're

Why mitochondria are important

27:03	working on a different mechanism which has to do with with increasing the
27:08	function and health of mitochondria using a compound that helps increase
27:14	nad now can you explain what nad is a little bit about why mitochondria are important and before you just want to
27:21	sort of back up a little and say that all the studies on aging that have shown any benefit to increased lifespan and
27:26	animals have all been often through calorie restriction which means you eat less like two thirds a third less
27:32	you live a third longer and and also new things like fast and mimicking diets are
27:37	being studied and other things related to calorie restriction now that that apparently affects the mitochondria that's how it
27:43	works and that's really what you're trying to figure out how do you get around having to starve yourself all the time yeah well the large part of it is
27:49	mitochondria um they do other things which we can touch on this they probably do 100 things that yeah that we'll we're
27:55	still working on um let's go back to yeast because i think that's a good framework in when we started in yeast we didn't know
28:01	why they were dying we figured that out it's mainly genome instability that that affects
28:07	their cell identity and then they die discovering the sirtuins was a game changer because what we figured out was
28:14	um there are three levels to aging um there's the base level which is the things that kill you
28:19	uh dna damage telomere shortening mitochondrial dysfunction okay that was pretty much
28:26	worked out in the 90s then there was a level above that that there were these regulators of aging the saturn's are
28:31	major regulators and and but then in the 2000s my lab and others found there was this
28:37	top layer which is the environment and when the environment is a little bit harsh
28:42	adversity or even perceived adversity it kicks these protectors into action
28:47	and then they slow down or reverse these causes of aging so think of it as a hierarchy pyramid yes what you want to
28:53	do is start at the top so how do you trick the body into thinking that it's
28:59	going to run out of food or that there's some other adversity and we found in yeast cells if you reduce the amount of
29:04	sugar getting back to sugar they kicked into action the sirtuins talk about how they did that in a minute
29:11	and then the yeast cells lived longer they protected the dna they boosted the mitochondria and they lived longer wait i just want to pause here so sugar
29:17	you're saying accelerates aging and restricting sugar actually helps increase longevity in
29:23	these wealth certainly for yeast and a lot of data on humans that lower sugar
29:28	is better and fasting blood sugar is lower is better too for longevity but there are other ways to kick these
29:34	returns into action uh so there's in humans um intermittent fasting is is easier i find than calorie
29:41	restriction i tried calorie restriction for a week it was pretty yeah i met a guy once who's i said he's doing calorie restriction
29:47	and he was a member of the calorie restriction society so what after breakfast i have five pounds of celery
29:53	and three pounds of tomatoes and i'm like uh no thank you

Intermittent fasting

29:59	well eating is one of life's pleasures but i find uh if for me if if i skip breakfast it's no big deal yeah right so
30:06	intermittent fasting is basically time-restricted eating where you eat within a certain time window of eight hours or or
30:12	ten hours right yeah there are plenty of varieties uh i talk about them in the book there are some other books that
30:17	talk about that um you mentioned this many times on your show the there are some
30:24	uh skipper meal protocols that skip two days a week yep there are some people uh
30:29	peter ortiz doing skip a week of food he says after three days magical things happen he thinks
30:35	i haven't tried that yet but i'm going to uh but yeah no one knows actually what the optimal
30:40	amount of fasting is what i can tell you is some time of being hungry is good
30:46	we can see that in our animals there's no question if we give our animals our mice food every other day they live longer
30:53	and in fact if we gave them resveratrol and the combination of eating other every other day we got some very long-lived mice and the combination was
31:00	great so that's one of the things i do to myself is get have resveratrol and try to be hungry once in a while that's
31:06	what the the okinawans are they call hare hachibu which is 80 false so you push yourself away from the table when
31:11	you're eighty percent fall there's a lot to that for sure you know having a lot of food and glucose in your bloodstream
31:17	just not a good thing so getting back to how to mimic uh this
31:23	mimic exercise and diet you can do it in in yeast you can do it in mice by
31:28	either taking resveratrol we showed that was one of the ways to activate sir to an enzyme that protects
31:34	the the body but we have something that's i think more interesting now which is the nad molecule you mentioned so nad
31:41	let me tell you what that is uh anyone who's studied biology will have heard of nad but probably forgotten
31:47	about it because it's a boring cycle yeah it's it's it's the molecule that nobody really wants to care about
31:53	yeah what we discovered uh is that it isn't just a housekeeping molecule for biochemical reactions germans discovered
32:00	100 years ago you needed it for life without it we're dead in 30 seconds but what became interesting was in uh thanks
32:06	to lenny's work when i was in his lab and then later in my lab we showed that the nad levels of an organism
32:11	are important for controlling the sertuan protective enzymes and as they get lower
32:17	they're not as active and if you can get them higher either artificially or by exercising or dieting they get kicked
32:24	into action we get the benefits of calorie restriction and exercise without actually having to do those things and the but they're added i don't that's a
32:31	good message no i was going to add to that which is but if you add them to you is that it
32:37	well we just published last year actually in the journal cell that if you have a mouse and you give it an nad boosting molecule and you
32:44	exercise then they become super mice and they can run okay that's good so you it's a
32:49	it's a lot of added value if you eat well and exercise oh definitely because i remember reading original studies way
32:55	back when and i was like wow these mouse these mice were eating terrible diets and they were metabolically younger they
33:01	were fitter and they didn't do any exercise i'm like whoa but then i was like wait a minute it's 1500 bottles of red wine it's not
33:08	gonna work yeah well in the research study we did show that you could you could live
33:13	make a mouse live just as long on a high fat diet um as a healthy mouse uh with resveratrol
33:20	in the diet but i don't want to send the message that that's all you have to do and you'll be fine no there's there's other things that that
33:26	go wrong and we're not mice after all um and you feel better if you're healthier
33:32	anyway right um so anyway getting back to the nab yeah we we can raise nad in
33:38	everything from a yeast to a human by giving them what are called nad boosters and these are
33:43	either nad itself or precursor molecules to allow the body to make an ad the one
33:49	that we use a lot in my lab is called nmn nicotinamide mononucleotide is its real name
33:54	and the cell cells in the body take it up there's a transporter they get sucked up into cells and they immediately convert it
34:01	into nad and we can see that there's a spike of nad produced after nmn after about two to three hours and then it
34:07	eventually goes back down but what we are seeing especially in mice where we can take out tissues i'll look at
34:13	tissues and blood is that that has phenomenal effects on the body's protective mechanisms through lightly
34:19	through the sertuans and mitochondrial activity so on the market there's a lot of these

Are resveratrol supplements safe

34:24	products out there that are being sold as nad or some varieties of them
34:29	combining them with resveratrol and is it ready for prime time should people
34:34	be running out and getting this stuff or is the data not there i mean is there clinical studies uh there are there are a few clinical
34:40	studies um so lenny guaranty and i he's my mentor we took two different paths
34:47	and i can only guess why i think one was that lenny's i think 15 years older than me and clinical trials take about a
34:53	decade so yeah he was in more of a rush than i was so he's gone supplement route and decided to use
35:00	that supplement to test in clinical trials and he's just had a a paper that came out i
35:05	think yesterday in parkinson's that looks really promising that parkinson's patients do better on his
35:10	um combination of an another na boost nad booster called nr which you can buy
35:17	and a resveratrol analog called terrorist stillbin now that's actually one of the first
35:23	studies if not the first that says that there's some positive benefits in people yeah they've been quite a few safety
35:28	studies and so far everything looks safe but i i know i just conjure the

Mitochondria and Parkinsons

35:34	main organelles are the things that get injured in parkinson's
35:39	and that mitochondria is exactly the cause of parkinson's science when the mitochondria aren't working well you
35:45	can't have proper motor function because it runs your muscles and they're easily damaged by toxins and other things so
35:51	using something that helps upregulate and i've had patients where i've given them nad and their parkinson's tremors
35:56	get better it's impressive fantastic yeah i hope that this is the the first glimmer that this is a really big change
36:04	in how we can approach many diseases not just parkinson's um the so lenny took
36:09	the supplement route i'm taking the pharmaceutical route um they're both going to be complementary there's no right way yeah we we have clinical
36:16	studies that are just finishing up phase one at harvard where things look good we can raise nad in humans and um
36:23	no sign of toxic effects our plan is to next year early next year go into diseases where mitochondrial are

Mitochondria and Diabetes

36:30	dysfunctional yeah we know for example in diabetes half of of of primary relatives of of type 2
36:37	diabetics like you know son under daughter brother scissors they have a 50 function of their mitochondria even if
36:42	they're quote healthy yeah so there's genetic things that regulate mitochondrial function that can be
36:48	inherited but then can be modified through some of these approaches well they can in going back to the mouth
36:53	studies we we could we showed i think 2013 now that within a week we could
36:58	make old dysfunctional mitochondria function and appear exactly like a young
37:04	animal's mitochondria in their muscle and to me that was remarkable because we were told that mitochondrial dysfunction
37:09	was largely due to my mutations that were irreversible and that we can find mutations there's
37:14	no question about that very late in life in a mouse and in humans they exist but if you catch it early enough and in
37:22	the case of a mouse it was about the age equivalent of a 60 year old we could turn a 60 year old equivalent mouse back
37:28	to a 20 30 year old within a week and to me that that defied all everything that we expected yeah it's true you know i

Mitochondria and Mercury

37:35	first became interested in mitochondria because mine stopped working really yeah i i had um
37:42	about 25 years ago i lived in china and i got exposed to a lot of mercury
37:48	and came back and got very sick uh from the mercury and and
37:54	it caused severe muscle damage and my muscle enzymes cbk was like 600 which is
38:00	really high and i had muscle fasciculations and twitching and aching and pain and i had severe chronic
38:06	fatigue and my systems just shut down i went from like riding my bike 100 miles a day to not being able to walk up the stairs my
38:12	cognitive function basically was like i felt like i was severely impaired i had add and
38:18	depression and dementia all at once it was really bad and so i began to sort of learn about
38:23	functional medicine and mitochondria and started treating myself by actually
38:29	upregulating all my mitochondrial pathways and all the cofactors and nutrients and removing the mercury
38:36	and i've used this approach in my and it made me get better my numbers are great and i feel good
38:41	and i see this a lot of my patients who have sort of these weird sort of mitochondrial problems like my wife has
38:47	this so if she goes for a walk or aerobic exercise she'll feel crappy afterwards and there's a syndrome of
38:53	patients who just when they exercise they don't get the runners high they don't feel good and they feel tired and
38:58	wiped out to take a nap and so i started saying well why don't we just try to give you a mitochondrial cocktail so i
39:03	gave her a whole bunch of things including nad coq10 carnitine ribose some amino acids
39:11	b vitamins i don't know something else maybe and uh and she would do that before she'd go
39:17	for a walk and no problem and i've seen this over and over again so i think you know
39:22	it's it's a lot of these things that we have to think about not just sort of one pathway right yeah well what's been
39:28	amazing to me is that we yeah we used to think aging and these diseases were one-way streets and we were lucky if a
39:35	medicine could help and slow down the disease but what you're saying and what i've learned is our bodies are remarkably
39:41	good at healing yeah better than we thought as long as you just tweak them the right way and we're at that point in medicine and history where we we have a
39:48	fundamental understanding it's not perfect we have a lot more to do future generations will look at us and think of us as primitive but we do have the the
39:56	tools right now to be able to change a lot of our disease um processes and our aging process as
40:03	well it doesn't surprise me that this is happening with my father he was going downhill he was approaching 80. he was
40:09	seeing his friends go downhill he started taking the anna man and saw in his view the same thing we saw in the
40:16	mice what we saw was it wasn't just mitochondria going up we actually found that the muscle started growing new capillaries or
40:23	capillaries as though they were being exercised and so he's bloody american and australian i try
40:28	that's right you've got a global audience so you may as well watching these english shows with my wife
40:34	she's from new zealand i literally have to pause the show and say what did they say and she's like we're watching the crown and you know i'm like what did she
40:41	say she like translates and then i'm like okay right or game of thrones like what did you say
40:48	yeah well stop me if i'm unintelligible no you're good you're kidding you've been here a long time so one of one of the things
40:54	that that is remarkable is so we one of the things i've i've found is that aging is also caused by a lack of blood flow
41:01	so build up of toxins lack of oxygen and by in inducing mitochondria to get them
41:07	healthy and give them more energy more of the ability to take in the nutrients
41:12	and get rid of the toxins in mice it's remarkable in people we think we'll be able to give them a lot
41:19	more vitality if my father's any indication of what we're going to see it's going to be remarkable we haven't
41:24	tested on vascular dementia but i'm hopeful that this could be a way around that too i've seen data somehow on

Inflammation and NAD

41:30	alzheimer's and nad2 right an amyloid yeah there's some at least in mice do
41:35	you know of any human results yeah in mice yeah no pretty exciting so
41:40	does nad also affect inflammation does it affect glucose and blood sugar and how does it work to those other
41:46	mechanisms that are so essential to aging yeah so the certains do a lot they control blood sugar they control liver
41:51	and and the pancreas the muscle um so they do a lot and often people say this sounds too good to be true but
41:57	it's not just my lab it's not hundreds of people working on this on the blood sugar side of things that was shown way back in 2012
42:04	by shin mi at washington university instant lewis um so yeah it does reduce blood sugar it controls the pancreas out
42:12	insulin levels it controls uptake of blood sugar on inflammation we know a
42:17	little less about that but my lab has done a fair bit we haven't published a lot but we find that
42:23	as macrophages one of the main inflammatory cells in the body as they become hyperinflammatory
42:30	they move into that stage that requires nad and if if you control that
42:37	and don't prevent and can and prevent them from chewing up their nad which they need to to convert
42:42	into the inflammatory state we suppress inflammation so what we're finding is if we give them our nad
42:49	booster or we block them from chewing up their nad as they convert into this inflammatory state we can reduce
42:56	inflammation and one of the problems with aging we think is that the nad levels of these cells and across the
43:01	body they go down with time and not so much in the bloodstream but in tissues we think that the levels of
43:08	nad such as the skin are we can measure that go down about half by the time you're 50. but at about a 60 year old
43:14	but i'm sure you you're looking after nad i'm hopefully i'm taking it yeah that that well that that certainly is a
43:21	way to boost it i like to sort of experiment on myself so i try different things how it works yeah uh me too um if we wait 30 years
43:29	for this all to be proven we will be gone by that point and my my view is what's the risk what's the benefit

RiskReward

43:34	what's the cost what do we know like is there a scientific premise that makes a reasonable explanation of why this
43:39	should work is it safe right does it cost a million dollars or 10
43:45	cents and you know just some simple metrics allows you to sort of try stuff with pretty much
43:51	impunity for sure well let's get into that because that's a good point um the nad levels are 50 you get them back
43:58	up to young level or even beyond that's when we see this reversal of aging so that i think
44:04	it makes sense what you're doing of course we don't have proof yet but we will a lot of people are doing iv is that better
44:09	i don't know we have we've done uh ip which is in the gut for mice yeah uh i
44:14	i've heard a lot about it um i think it makes sense that that that should work just just as well
44:21	but getting back to the risk reward thing of that that's really important so it's a fact that a lot of these molecules are relatively cheap um
44:29	in the case of metformin what is it less than a dollar a day might be a few cents a day for some countries okay so that's not a
44:35	lot of money all right that's that's that's the cost what's the risk something like metformin has been in
44:42	probably a hundred million people used for the last 40 years risk is extremely low oh there's some side effects like gut issues and things
44:48	yeah exactly you're a real doctor i'm just a phd but metformin you can have you know i think the biggest risk is
44:55	you'll have an upset stomach but there can be some severe side effects you'll want to do these you want to do these things under medical supervision do some
45:01	blood tests okay so now we know the cost we know the risk okay so just use metformin as an example
45:07	um the the downside what's the upside well
45:12	the upside is you you might have a few extra years maybe another five years of healthy longer life
45:18	that's a pretty good trade-off yeah um what i think what most people have trouble
45:23	in the calculation that we just did and you and i have done this calculation similarly is what's the risk if i don't do
45:30	anything yeah all right but most people are in denial you know when you when you're five years old you realize that
45:37	everything dies your parents you'll die it's horrifying every kid goes through this and we we don't remember typically
45:43	going through this i remember you know it's horrifying that may be why you you and i do what we do because we have
45:49	we've we haven't forgotten the shock but i think most of us we don't we don't like to think about this every day yeah
45:56	it takes a lot of guts to think about your loved one's mortality and it's even worse if you seriously contemplate your
46:01	own mortality every day that's that's brutal you don't want to do that but if you if you do think about it at least
46:07	you know once in a while that calculation that we just did becomes pretty easy to do yeah um
46:14	yeah it's it's pretty scary what what is going to happen to everybody it's not pretty um and we're all in
46:20	denial that this is something that we might be able to do something about and that's what i'm talking about in the

Lifespan

46:26	book is so you this book lifespan the revolutionary science of why we age and why we don't have to
46:31	uh is is kind of a manifesto for how we can think differently about aging and
46:37	the things we can actually do to slow or even reverse aging i first
46:42	really got interested in the whole science of aging when i went to this conference i don't even know if you were there was uh with the dalai lama
46:49	it was at robert thurman uma thurman's dad's place up in um
46:55	a mental retreat in upstate new york and there was all these tibetan doctors and dilemma but all these extraordinary
47:01	scientists people like elizabeth blackburn who studies telomeres and leonard guarta who was one of your mentors at mit who studied aging
47:09	and i remember just sort of walking down the field with leonard and saying so what is the deal with aging why do we
47:14	age and essentially and how do these certuans work and what's driving them and how do they get regulated and
47:22	what he said to me was shouldn't have been surprising but it was kind of surprising it was like sugar like sugar is the thing that's screwing up our
47:28	aging process and our mitochondria and that's what actually causes these sirtuins not to function the way they
47:34	should and i thought wow that's fascinating and it sort of got me thinking about the whole process of aging
47:39	and then um i was watching one of your interviews online and you you mentioned that you
47:46	are um obviously studying aging but you're also looking at your own aging and you did
47:53	some tests that indicated that you were older than you actually were chronologically and then you did some things and you actually found that you
48:00	were younger than you were chronologically so how did that work what just let's start with your own
48:05	journey of how you actually made yourself younger well yeah cause you're the guy who knows
48:10	about this stuff uh well i gotta say you're turning 60 i wouldn't have thought so so whatever you're doing keep doing that and look at
48:17	him he's like awesome looking uh well so this is the book lifespan that's an awesome book well that this is
48:24	uh a download of my brain into that book uh of everything that i've thought about over the last 25-30 years
48:30	uh in terms of my age you know this is not a clinical trial so i'm not going to be publishing these data anytime soon nf1 is good nf1
48:37	but you know when you're on the cutting edge of science you start with an n of one all science begins that way um
48:42	so what i did was i went to a company that does blood tests should i mention
48:48	their name doesn't matter to me inside tracker i'm a consultant to them if anyone wants to know
48:54	and they have a a five uh factor blood test that
48:59	goes with proven correlates for longevity so glucose ferment testosterone liver function
49:06	uh crp um there might be one thing i'm missing but those things uh add up blood sugar
49:12	inflammation definitely blood sugar is a major thing for aging actually one of the best predictors of your life span is
49:19	your blood fasting blood sugar yeah so yeah it does and by the way not not within the normal range it should be
49:25	optimal right so if we consider normal up to 100 but if you're going get up to 100 it's not good right oh yeah we could
49:31	get into that i i find it crazy that a lot of times we don't treat high blood sugar until it's too late yeah anyway so
49:38	the so what i did was i had my blood tested and i i've been doing it since 2011 i've seen things creep up as i got
49:45	older uh and at the time i was 48 when i had this test
49:51	uh when i got a real shock that it said that i was 58 oh wow ostensibly for the the aging researcher to be 10 years
49:57	older not a good look because it's not a good thing yeah right right i i'm worried i might die from a heart attack
50:03	and they want to go okay i'm writing this book about lifespan but i'm actually like way older than i look right that would be bad so uh i did a
50:11	couple of things um i started taking uh metformin actually so this is the many
50:16	people know this is the frontline therapy for type 2 diabetes yes and i felt justified doing that for two
50:22	reasons one is i'm a scientist i can see what happens um it's fairly safe drug
50:27	we can talk about to safety but millions of people have tried it and i also have high blood sugar in my
50:34	family and it was edging up so my father's on it my grandmother was on it so i figured why not start before it
50:40	gets out of control so that was the science part of me uh and then i also um
50:46	well i saw my age come down a little bit a few months after that it wasn't great it was better yeah i
50:52	came so i started out at 58 and i was a bit worried what came down to about 57
50:57	56 as i recall not that great no no it's still still not good so i went on uh
51:03	the molecule that we were studying in the lab which we were giving to mice and we could see was improving their health
51:08	and making them run further and as far as you could tell reversing some aspects of aging particularly in muscle
51:14	and i started taking it again just as an experiment not as a clinical
51:19	trial and next time i measured again a few months later it went down to
51:25	uh 31.4 amazing so you're now older but younger
51:30	well it was a good day i my wife would tell you i was running around showing her the graph going look at this independent studies show i'm younger
51:38	and it it stayed down and um but one thing that happened was with combination of these two things i wasn't as hungry i
51:45	lost a bit of weight about seven pounds which certainly wouldn't have hurt um but one thing about the
51:51	this inside tracker thing and other things such as i noticed you i think that's what same ring as i've got yeah
51:56	the ordering when you've got data in front of you every day you think more about it and you can react and and
52:02	before i would never know what was going on if i did something to my body yeah now they have these continuous glucose monitoring yeah yeah and that that bio
52:09	feedback the bio tracking as we call it um it's beneficial in in nothing more if if
52:15	nothing more just gives you more clarity about how you're doing and more mindfulness we know more about our cars
52:22	than we know about our bodies actually with all the sensors over 100 sensors in our cars how many do we have on our bodies yeah
52:28	eventually we'll have many more so what does it look like 10 20 50 years from now in terms of aging i mean i'm

Future of Aging

52:34	you know turning 60 i'm like what's going to happen in the next 20 30 years in this aging research and what's coming
52:40	on the horizon that's going to help me live long and meet my great grandchildren
52:45	yeah well so i've been blown away because it's all about me after all right i just want to
52:51	live longer well sure i mean if if we're all honest we don't want to get sick and we do want to see what the future looks
52:56	like most of us well so the last 10 years have been remarkable just made my head spin we can we can
53:03	challenge and test high policies in a week things that used to take a decade
53:08	so the the power that we now have these hallmarks of aging that we've all in the field agreed on cause aging mitochondrial dysfunction
53:15	telomeres uh we've heard the mold pretty much senescence cells i mentioned um there's been a new
53:22	change um and it's we're undergoing a new paradigm shift and it's it's a it's a theory that i put in
53:29	the book called the information information theory of aging and the idea is that all of these
53:35	hallmarks actually are manifested by a loss of sailor information from when we when we were young and
53:42	essentially what that means is that our genomes which have the digital information in our bodies
53:48	are largely intact it's the reason we can reverse mitochondrial aging pretty quickly in an old mouse it still has the
53:54	information to do that in its genome the problem is that we have this other type of information called the epigenome
54:00	which is the next layer of information that controls the digital yeah so it's similar to a dvd player uh the
54:08	the information's on the disk but the ability to read the songs at the right time degrades uh over time and so the
54:15	epigenome gets uh less and less accurate and it's similar to scratching the dvd and you
54:21	can't read the genes at the right time you can't read the songs and what i've been
54:27	questioning uh or at least curious about for the last 10 years and what's funny
54:32	let me just tell you something mark as a secret with millions of people is that
54:38	um i've been so busy i haven't written a lot of these ideas down in scientific publications
54:43	i've been working on the book yeah so it could be that the world will be able to read about all this science before a
54:50	scientist do which is very unusual um we are about to uh submit these so
54:56	what am i what is the idea is that if you scratch the cd do you end up with premature aging and
55:02	we've done that now in a mouse we can actually do that we can mess up the epigenome and the mice get rapidly old
55:08	and actually we can measure their age now we've got what's called the epigenetic clock or the horvath clock named after steve
55:15	horvath and we can do that i could take your blood and measure your biological age very
55:21	accurately okay i'm coming in we should both do that i haven't done it yet for myself uh but those mice we can
55:27	accelerate their actual age they're not just looking old they're old and so that's the scratch dvd the
55:32	question is is there a way to polish that and get back the ability to read our genomes correctly like we were young
55:38	again and i think we've figured out a way to do that and that's what what
55:43	we're working on we have this i can't say too much because i'll scoop not only the book but my publications
55:50	but we've got this combination of genes that tells the cell how to be young again and reverse that
55:56	clock of aging the epigenetic clock and polish the cd and one of the things that's been remarkable is that if we
56:02	take an organ or an or a part of the body that normally would never get young never would regenerate and we chose the
56:08	hardest thing of all which is the eye we looked at old eyes or damaged optic
56:14	nerves we can actually damage them or glaucoma these are things that right now you just can't reverse you're lucky if
56:20	you can slow them down if we give our reprogramming treatment and it's it is a gene therapy currently
56:26	we put in the eye and old mice can see like were young again within just a few weeks of treatment it's like jesus
56:32	well yeah that's why i see right well i went when we discovered this and i have to give full credit to my collaborators
56:38	at harvard who actually do this i don't know how to do it but they're exposed i went home and said to my family we've
56:44	cured blindness in old mice you know who cares right my kids went uh yeah that's fine um can
56:50	you set the table and my wife goes oh no first can you empty the dishwasher come on jesus got respect what's going
56:56	on yeah but it's it's early days but i think that we've we've cracked a big one is that we don't don't just slightly
57:04	reverse aging we might actually truly reprogram the body this is so exciting hey youtube if you like this video