171- Longevity science: caloric restriction studies, aging biomarkers & possible longevity molecules

Steve Austad is a distinguished professor of biology at the University of Alabama and director of one of the Nathan Shock Centers of Excellence in aging biology. Steve's current research seeks to understand the underlying causes of aging, specifically with a long-term goal of developing medical interventions that slow the age-related decay of human health. In this episode, Steve tells Peter about his unusual childhood and stints as a cab driver and lion tamer. He goes on to describe what led to his focus on studying aging and some of the major challenges and limitations of working with laboratory animals. Steve and Peter talk about the relationship between caloric restriction and lifespan, including some of the most important studies exploring this question. Additionally, they hypothesize what might explain the sex-related differences in longevity between men and women, explain the importance of finding longevity biomarkers, and discuss the most promising molecules as potential longevity agents.
We discuss:
00:00:00 - Intro
00:00:10 - Steve’s background and unusual childhood
00:07:19 - Steve’s adventures driving a cab in New York City
00:12:11 - How Steve drove to LA and accidentally became a lion tamer
00:22:18 - How Steve’s early graduate school experiences led him to study longevity
00:30:35 - The challenges and limitations of working with lab mice
00:43:49 - The connection between caloric restriction and lifespan
00:52:30 - Mice vs. rats and rodent aging experiments
00:57:32 - The impact of dietary composition and the harm of sucrose: Comparing two caloric-restriction studies in monkeys
01:12:22 - Challenges of studying animals due to major differences in the lab animal vs. wild animals
01:28:22 - Human studies of calorie restriction
01:37:18 - Better dietary protocols for humans: Alternatives to long-term caloric restriction
01:42:12 - The protective effect of fasting
01:50:53 - Reflecting on the sex differences in human lifespan, and why women have more neurodegenerative diseases
02:10:17 - The importance of identifying longevity biomarkers and which ones show the potential to change the landscape of longevity research
02:21:35 - Molecules showing the most promise as longevity agents
Show notes page: peterattiamd.com/steveaustad/
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About:
The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 30 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.
Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life).
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[@PeterAttiaMD]

In this episode we discuss: 00:00:00 - Intro 00:00:10 - Steve’s background and unusual childhood 00:07:19 - Steve’s adventures driving a cab in New York City 00:12:11 - How Steve drove to LA and accidentally became a lion tamer 00:22:18 - How Steve’s early graduate school experiences led him to study longevity 00:30:35 - The challenges and limitations of working with lab mice 00:43:49 - The connection between caloric restriction and lifespan 00:52:30 - Mice vs. rats and rodent aging experiments 00:57:32 - The impact of dietary composition and the harm of sucrose: Comparing two caloric-restriction studies in monkeys 01:12:22 - Challenges of studying animals due to major differences in the lab animal vs. wild animals 01:28:22 - Human studies of calorie restriction 01:37:18 - Better dietary protocols for humans: Alternatives to long-term caloric restriction 01:42:12 - The protective effect of fasting 01:50:53 - Reflecting on the sex differences in human lifespan, and why women have more neurodegenerative diseases 02:10:17 - The importance of identifying longevity biomarkers and which ones show the potential to change the landscape of longevity research 02:21:35 - Molecules showing the most promise as longevity agents

[@NunoCordeiroPT]

1:57 "There are many that get no X chromossome. They get two Ys." Lack of X chromosome is incompatible with life. There are several variants like XYY... maybe that's what you meant.

[@Beginnerarttutorials]

Wow! That story with the lion and his youth in general would make a great movie!

[@ItsBlissfulAcres]

The movie is called "Roar"

[@patrickwhelan2656]

This is very good. When you have a cursory knowledge of a subject, like I have, it’s easy to get swayed by a superficial read of an abstract or watch a podcast by a scientist perhaps with a book to sell or a project to push - no names mentioned, but we can all think of a few - whereas these two gentlemen give a non-biased deep dive into the subject matter.

[@TheBroSplit]

This guy had some stories to tell. Man ! Great podcast

[@espinosalexis]

Well said Dr. Steve! The same thing I said about the Richard Miller's "gold standard tests for longevity": they are finding that diabetes drugs extend life of mice in their experiments. I say: of course, if they give them a diabetes-producing diet to the mice, then yes, those drugs of course will help. But the control group should be eating a much better diet than the chow they give them. Then, from there, longevity drugs should be tested. So, yes, it is very important to find the ideal diets (and life style) for the lab mice and rats to start with.

[@jackiebardsley9946]

Thank you - another great interview. I always learn so much.

[@craigm7240]

I cannot believe how educational this was.

[@elbay2]

Fascinating discussion… thank you!

[@scottgilliland2061]

Ouch, as a 5’7” person, I was saddened to hear I’m not normal 😝 Great video, as always! Thank you for sharing these great conversations with us, I always learn a lot.

[@mary_puffin]

Haha. I laughed at that too. I don't think Peter is much taller, so you're in good company. :)

[@iss8504]

5'9" is average height for guys ie Peter's height. I think he is also including weight in his discussion. Steve was really short and light before...5'4' is small for a guy.

[@elizabethk3238]

You just didn't want to know...

[@richardlawson6787]

Cheer up....studies show tall people don't live as long as short people

[@awnzotheman]

5'7 perfect.

[@nadernayo]

wow.. Lots of knowledge.. Thanks peter for making this knowledge available to us..

[@lucretiasulimay1968]

My best friend, Diane, and I were just talking about how we can't believe we are still alive!! We are 64 , after all the crazy things we did in our early 20ies !!!! Thank you for the laughs and great conversation and information !!

[@markveen1373]

I've seen a woman in pristine condition at age 103. Could still walk without any help. Clear voice and hold long conversations. Hardly any wrinkles. Looked like a healthy 75 year old. Doctor checkups every season. Everything seemed more then fine for her age. One summer day however she took a midday nap and was gone. With a smile on her face. Family told nothing strange was going on the day before. I would imagine at those extreme ages. You would need to have a very strong will to live, and still have goals. If you're happy and content. Did everything you wanted to do. The body just gives up I think, eventhough it could go on for longer. Ultimately, the mind controls the body.

[@knowledgelibrary1141]

At any age, purpose is what fuels human life. Hence why most people "die" very early in life. They navigate the world without purpose and live cookie-cutter lives until they reach old age and then pass away. I would argue that the elderly person you speak of live ten lives relative to others as clearly something kept her going for many decades beyond average human life span.

[@iss8504]

Absolutely you are right. My father in law was a spry 85 year old, living independently and he had an accident that resulted in a leg injury that ended his independence. He had to live in a nursing home. He couldn't drive or cook or do amything without help. He lasted a year. Refused to leave his room. He was a social guy. He just gave up on life.

[@elizabethk3238]

At 74 the only goal I have is doing what it takes to remain healthy. Some need GOALS (usually those who have not yet begun to examine their lives), those of us who have done self examination just enjoy living in the present.

[@gloriasaliba3395]

@@elizabethk3238 agreed - I’ve contributed much to my family work friends and the community I live in - it’s now my time to focus on me - walking Pilates strength training reading books from cover to cover being mindful and relaxed when cooking spending time with friends long lunches the cinema opera ballet spending quality time with the second generation in my family and treasured sleep ins - when people ask me how I spend my day I just smile

[@kirstinstrand6292]

I've heard it said that we can choose when to die; my mother did. ❤

[@IvicaOS]

what a great guest, as always…🤗 what a great pod, as always…👊🏻

[@armandsriekstins7646]

This was really good!

[@khaledzurikat7190]

Genius person with unlimited humility!

[@HkFinn83]

59:02 Squirrel monkeys, my spirit animal

[@bottymcbotface007]

"But you're a normal sized person, its not as if you are 5'7 now, so where did the growth spurt come from?" 5'7 man crying here :'( Thanks Peter! Made my day!

[@kirstinstrand6292]

Got a growth hormone injection during childhood.

[@focusedvegetable3655]

Loved his background and overall perspective. I am not sure I would known him to be such an exciting scientist from his papers.

[@carlaharmon4552]

This is AMAZING!

[@melisasurprisebox9978]

This is the best episode that i’ve ever had on yours for fun. I heard this one third time and I still laugh about the lion.

[@Dan-jo8py]

"As rats they're fatter, more diseased, reach puberty quicker, have too many kids" ...sounds the perfect model for human research to me.

[@tonynoonan3723]

Thanks Dr Attia, Great Podcast,whats your view on giving metformin to an asymptomatic patient with 35% generalized coronary artery plaque deposits with a view to stabilising the disease process..

[@jakobw135]

So which has a more positive effect overall on your health: caloric restriction, or time restricted eating?

[@ES-qe1nh]

CR irrespective of timing is what matters. TRF makes CR easier for some people. Unclear if TRF by definition has additional benefits over CR

[@bernhardwalther]

Great content! Thanks for being so accurate. I heard the way is long to go for people over 40. Let's hope to be lucky on rapamycine very soon...

[@tablecork]

I think we would all would like to know what they injected him with in high school, could've used some myself! LOL

[@joetart9905]

Would love a interview with Dr Ron Rosedale!

[@cryptomusician4039]

At the age of 72, I am at 20 a year low point at 239 lbs. It is now 30:00 of an extremely interesting KZbin and I am on a calorie restricted nutritious diet. Will continue to watch and report...

[@kirstinstrand6292]

What's your height?

[@HkFinn83]

As a person who is natural...weight gainer, fasting is one of the only things that works for me, good luck:) Edit, comments a year old, hope it’s going well😂

[@y.g.1313]

2:11:08 - NIA (National institute of aging) in 1990 rec'd $100M for biomarkers of aging and got nothing. - probably the most valuable statement in the whole interview.

[@anthonylawrence5842]

I have a personalised story and n of 1 but I seem to have established an interesting effect. I am aged 69. I have worked out for the last 45 years 3 times per week HIIT and HIRT for 1 hour. The last 5 years fairly strict Keto diet, almost no sugar and starch and only complex carbs. (no nuts I'm allergic) I weigh 70kg at 5'10" height. I take a daily, limited but strict, daily supplement stack daily. I use IF only, eating within a 6 hour window twice per day between 1pm and 7pm. I have recently had a GlycanAge Test for biological age. It came back at 32 (they've never seen this out of 150,000 subjects). Interestingly, I have recently increased my calorie intake by at least 400 calories using natural yoghurt, double cream, pure Whey protein powder and a few blueberries. In a month it has made no difference to my baseline weight. Anyway, seems to be interesting so far?

[@LTPottenger]

Great! You are getting the result everyone hopes is possible. Do you do any longer fasts?

[@anthonylawrence5842]

@@LTPottenger No, just the daily 6 hour window 1pm to 7pm. Small daily supplement stack. Multi B complex with C, Calcium AKG, Vit E (only Tocotrienol) Omega3 (only DHA) Seaweed caps, Adaptogens, Pottasium and slow release Magnesium, K2 (special formulation) CoQ10 with Resveratrol, Phospholipid complex, mixed Japanese mushroom complex.

[@oolala53]

@@anthonylawrence5842 May I ask what you spend on a monthly basis on supplements? You have ahd good results, though you are doing so many things that it could be hard to determine if something wasn't actually optimal. Longevity researcher Valter Longo has said that the only daily fasting window that has not shown any issues is 12 hours. Also, what do you mean by complex carb? I thought it was pretty hard to have what I think of as complex carb at all on keto. In any case, you have found a lifestyle that gets you what you want!

[@anthonylawrence5842]

@@oolala53 Hi - I spend in the region of £150 per month on supplements. I workout 3 to 4 times a week - 15 minutes HIIT and 45min to one hour with weights. At now 70, maintaining muscle mass is more important than aerobics. I can drop the weight and increase the reps. I'm not too religious about keto but the complex carbs are usually cruciferous vegetables, avocados, avacado and selective nuts. (not cashews or peanuts) I only use avacado and coconut oil. No fruit at all - I use fermented veg and Inulin for fibre. (awesome!) BTW I can still bench press at world championship level for my age and weight!

[@oolala53]

@@anthonylawrence5842 Goodness! You have to admit that is quite a big budget for supplements, though obviously worth it to you. I thought to maintain muscle a person would want to keep weight high. I guess you buy inulin separately. I eat about a half a cup of fermented veg a day. That doesn't amount to much fiber, but magnesium helps as well as some greens. Do you eat mostly fatty meats for the core of your calories? I don't mean to be disrespectful but in first post you said you had a fairly strict keto diet but later said you are not too religious about it. I guess that just means you don't have a hard-and-fast limit, but know from experience where you land with your plant intake. Fair enough! Your consistent exercise regimen sure keeps you in the elite! Reminds me of a former Crossfit champion who changed his sights and dropped way back in training. His former life, though resulting in a strong body, also wore him out. What he does now he says he can continue for decades. I believe his name is Marcus Filley. Maybe he should be featuring you in a video!

[@loginusers5812]

I would want to be part of calorific or dietary restriction studies and I promise to follow them diligently.

[@pavelchorda8425]

Great interview. As a biologist, I was always interested in longevity, my thirst of knowledge brought me to Studie Taoism (I was doing martial arts since I was 4), I went deep into the topic and in the practice, the point here is, in men the shortering of life span comes directly from the loss of jingchi, directly associated to the loss of sperm, Of course as animals we need to pass on our genetics to the next generation, improving if it's possible 😉, This could be the relationship between sexual hormones, longevity. It's a long topic

[@digantasarma7727]

I think we should also observe people around us. I have seen many who eat less and active and are healthy in their seventies.

[@cbbhvjc]

Dr. Attia, please activate KZbin's "Clip" feature.

[@happynjoyousnfree]

OMG how were you not laughing HYSTERICALLY at the lion story??? I would have been rolling on the floor 🤣🤣🤣🤣🤣

[@aquamarine99911]

tl/dr We still don't know anything, because we don't yet have the appropriate biomarkers for judging the efficacy of rapamycin, metformin, fasting, NAD enhancer or whatever. But still an excellent conversation.

[@jeffrey4577]

Which mice species does valter lingo use?

[@scottk1525]

I think the monkey studies prove one thing: excessive sugar is a death sentence.

[@t.t.8878]

My mother ate large amount of sugar all her life. She never exercised ,& never took any meds or vitamins. She liver to be 89 & died in her bed reading the bible.

[@scottk1525]

@@t.t.8878 Oh well in that case, we should all stop exercising and eating healthy because it clearly doesn't matter. Nice work. Make sure to call Attia. I think he still believes that exercise is healthy and sugar is harmful. Crazy, I know.

1:56:50 I don’t think a human embryo with a 46,YY karyotype would be viable (or a human embryo with any total monosomy other than 45,X).

[@sciencesimplified3890]

im starting to really agree that methylation clocks are just a big effort to find a signal in a bunch of noise.. but its mostly just noise or different proxys for different things depending on the clock.. like im sorry if a certain lifestyle reverses clock by 6 years, does that mean that lifestyle will make you age in reverse in live forever? of course not.. of course its all more nuanced different clocks are measuring different things but it is starting to feel like hype

[@spek2554]

I have listened to many talks on this subject of calorie restriction and it seems that the message is the more that your body struggles to stay alive by not starving to death, the longer you do stay alive. Dietary hormesis. As though it is mutating everything to achieve that goal. SAD dieters are telling their bodies “hey, I am satisfied, it’s a great time to die.”

[@lk-ky3rw]

I find it interesting that Dr Attia is chasing longevity and yet the activities he participates in are higher risk such as extreme swimming or car racing, quite the paradox... almost like he can't get rid of the thrill seeking aspect of his life

[@iss8504]

Forever consists of nows. You're better off having lived and experienced than just living a long time and avoiding risk. Life is an adventure !

[@oolala53]

I believe he has curtailed a lot of his extreme activities because of that very issue.

[@BubbaBeast321Go]

Is that a picture of Richard Feynman in Peter's office?

[@peterz53]

Yes

[@LTPottenger]

good eye

[@RanAmitay]

1:25:50 is a small Easter egg. Loved this discussion!

[@kirstinstrand6292]

After listening here, it seems that longevity studies are just getting started. Oddly, I always find myself agreeing with Dr. Attia's judgement.

[@ES-qe1nh]

Indeed! At least the rigorous, useful ones

[@LTPottenger]

Sounds like there is zero benefit to caloric restriction than not overeating and a lot of drawbacks. Now let's see fixed ad libitum compared to fixed healthy diet compared to 23:1 compared to fasting one day and eating ad libitum, fixed budget and or 23:1 on the eating day. Then maybe we will get some idea if the actual lifespan can be improved

[@Chris_Kunce]

The story about the CR mice that were climbing the cage was interesting. Presumably they were devouring their food and incidentally eating OMAD. Could you pair feed two mice, both CR, but one OMAD and the other in a time-released schedule that mimicked meals and snacks? Would there different outcomes?

[@elvay6847]

02:24:45 LOL guess he hasn't turned on a television in a year.

[@AlexEats]

I’ll volunteer

[@korchansan]

Wow this guy took an arrow to the knee and lived to tell the tale

[@johnditraglia8345]

Dr. Austad that's called constitutional short stature (that also runs in families like familial short stature) where you go through puberty later and finally wind up more average height. 0

[@espinosalexis]

As my past 12 comments: Everytime you touch this topic I wonder when are you going to invite Prof. Longo to your show? Or, put in other way, I wonder if you guys don't like each other? It appears incredible to me that Longo has not been yet in "The drive"!

[@doctork1708]

Lingo probably disagrees with his life philosophies.

[@LTPottenger]

Where is longo though? That may be an issue

[@oolala53]

@@LTPottenger He works in Italy and Los Angeles. Yeah, he would have a lot of contradictory interpretations.

[@iss8504]

@10:40 NYC is back to the 70s. I used to live in NYC , glad i am not there now. The stabbings and random attacks...its back to Batman's Gotham.

[@junepagan8715]

Profilings offered a calorie restricted program at 1200 calories.

[@zack_120]

20:20, 34:45, 1:57:35

[@BigPictureYT]

Not only are the lab mice genetically bizarre, their environment is totally weird. Wild mice are nocturnal. They forage. They interact with other mice. They are not locked in prisons and feed balanced meals without exerting any effort.

[@QueOndaWhey]

Clearly haven't been to #NYC recently....

[@LTPottenger]

heh

[@moontrack4625]

Concerning that all lab research with these meices may have almost no real scientific applications r/t humans!

[@LTPottenger]

I don't think that's true. Being homogenous has a lot of benefits.

[@peterz53]

Keeping monkeys caged for decades, alone in small cages, was extremely inhumane. Brutal. Don't understand how this could be allowed.

[@HkFinn83]

We still do it to humans

[@riddlescom]

I'm glad I'm not a mouse.

[@Thomas-kx5nj]

Vous avez bon cœur et nous vous sommes reconnaissants pour tout ce que vous faites Dr akhande Merci de nous avoir fourni le traitement contre l'herpès 1:28.

[@mightbefire]

1:43:00 Who are these monsters? This is the path to Josef Mengele. You can do whatever you want, and feel justified, as long as you decide something’s pain, suffering, or even life, doesn’t matter.

[@trismegistus3461]

tl;dr what can we (humans) do to increase longevity?

[@ES-qe1nh]

Exercise, have friends, avoid saturated fat, ingest DHA/EPA, get your APOE alleles and Lp(a)+ApoB checked

[@user-87jnfdcssbmjj]

Good overall but the conversation about the origins of risk-taking behaviors in young men vs. women veered off in a real non-scientific and clueless direction

[@user-po7te6hn2s]

talk to programmer who improves code of "blind programmer" like Nature is

[@TheBroSplit]

Right away hearing about the kidney blood restriction test on mice seems cruel to me. Like we are nazis and other species are the test subjects

[@AlexEats]

I balance my 5 days of 1k calories with two days of 5-7k days. Get yo weight up 💪😂

[@Ayrad160]

How can you be on a calorie deficit your whole life without losing all your fat

[@kicknadeadcat]

Labs are now getting away from rats and have settled on lawyers. For 2 reasons…..lab technicians do not get as attached to the lawyers and lawyers will do things the rats won’t. Robin Williams……

[@johnbaker8742]

Haha

[@neilpbullock157]

Almost half way thru and no specific health, medical or research data beneficial toward aging. These basic approaches & insights could have been covered in 10 min or less.

[@kirstinstrand6292]

I eventually skipped ahead. lol

[@user-po7te6hn2s]

just for the record: in this episode Peter is dead-wrong on epi-genomic info for longevity-science.

[@pimvisser3874]

Elaborate?

[@user-po7te6hn2s]

@@pimvisser3874 will do once paper released

[@pimvisser3874]

@@user-po7te6hn2s ETA :D

[@quantumuniverse5771]

X longevity is way big area, you need to be a bit specific when you're saying smt like that!

[@bugsbunny2357]

Somehow the idiocy of men I do not find surprising. LOL I have no doubt the difference is testosterone (but, then again, it's not my job to prove it).

[@elvay6847]

Idiotic yet better at just about everything ♂

[@mary_puffin]

@@elvay6847 Better at caretaking and childbearing too? LOL. What a sexist comment! Men and women contribute differently - you don't have to put women down to say men are good at something.

[@MikeG-js1jt]

Stupid behavior like swimming the Catalina channel?................. stuff like that?

[@mikefinlayson9907]

Why is it a “problem” that women live longer? Other than an intellectual perspective?

[@csn583]

"CO2 is highly sedating", Peter?! Sure you're not thinking of CO? For obvious reasons, CO2 buildup is the MOST guaranteed fear-inducing environment across all sorts of air-breathing lifeforms. Dragging that on longer could maybe have a frog-in-boiling-water effect; that could be the logic to the new methodology. But while 5 seconds may not be long to suffer it, that is a final shot of adrenaline as sure as a bag over the head. Surprising flaw in thinking in what was otherwise impressive diligence in fighting bias. Perhaps what it takes to internally justify exterminating hundreds of thousands of animals as a career is a bit of a blind spot. Doubt me? Try it. Bring a friend so you don't kill yourself.

[@brookstorm9789]

Such an entitled attitude about torturing animals for things that could be easily known through common sense and anecdotal evidence. It seems just that the main torturer dies of a violent injury himself. "I don't think the animal research tells us that much about people". He admits it. These people are not wise or compassionate. The animals also have the mind of God, the full spectrum of feeling and suffer greatly. Look at the researcher's face and hear his broken voice. Nothing he has done has benefited him or anyone The human population is being used as lab rats as well and how has that worked out?

[@ES-qe1nh]

What?