Recently stumbled on a lot of interviews with longevity scientist and researcher David Sinclair. Many on YouTube. He is saying that research is showing that eating less and having longer periods of fasting activate genes that keep us younger and healthier. He is eating a mostly plant based diet. He has been basically eating one decent size meal a day for the past several years and says he feels better and looks younger. Some of the keys being a long period of fasting. Keeping glucose levels as low as possible. Just wondering what some of you thought about his ideas and research if you are familiar with it.
Guided_by_Voices
Well-Known Member
Anti-aging is a huge topic. I would recommend Josh Mittledorf's Aging Matters Blog and Paul Jaminet's Perfect Health Diet as a starter set of reading. One of the primary mechanisms behind Time Restricted Eating seems to be keeping insulin down, since chronically elevated insulin seems to drive almost every major disease state (Cancer, Dementia, CVD, and others.) Paul Jaminet has an excellent view on what healthy plant-based really means, and it doesn't mean there is anything inherently wrong with animal products.
Deleted member 16042
Member
Contoversial. Sinclair's work on resveratrol has apparently been debunked. His results could not be replicated. In the meantime he made 720 million selling the technology to Glaxo.
Is Sinclair or Stanfield bunk?
Is Sinclair or Stanfield bunk?
SteveCleves
Well-Known Member
I think its pretty well accepted as conventional wisdom in the longevity world that calorie restriction, whether through actual calorie restriction or through tricking the body into thinking your calorie restricted, is a key to longevity.
At the risk of "knowing just enough to sound stupid"...I think the theory is basically when the body thinks its starving it slows down all the growth and aging systems.
At the risk of "knowing just enough to sound stupid"...I think the theory is basically when the body thinks its starving it slows down all the growth and aging systems.
FunkOdyssey
Seeker of Wisdom
I was a moderator of a longevity forum for many years, called the Immortality Institute in the early days and now Longecity.org. That gave me a front row seat to the rise and fall of resveratrol and Sinclair's fall from grace along with it. Somehow, he has managed to rebrand himself as the public face of anti-aging science after writing a very popular book, Lifespan: Why We Age and Why We Don't Have To.
The most exciting compounds available right now are rapamycin and senolytics, including fisetin, dasatinib, and quercetin. These may actually slow or reverse signs of aging. Rapamycin consistently extends lifespan in animal studies even when started in mid or late life. I've been trying to get my father to start on it with Dr. Alan Green who prescribes it via telemedicine.
Peter Attia doesn't have a book but he is a better source of information in my opinion if the topic interests you.
peterattiamd.com
Back to Sinclair, listen to him talk for five minutes about TRT and why he thinks it will shorten our lifespans in this podcast:
The basis for his opinion is purely theoretical: factors that suppress growth and reproduction generally extend life (IGF-1 knockout, mTOR inhibition, calorie restriction). Testosterone supports tissue growth and reproduction so it must shorten lifespan.
Two of the very best predictors of how much time you have left are your grip strength and walking speed. What effect do you think testosterone will have on those parameters?
The only facts cited to support his position are that eunuchs have been observed to live longer than intact males. There is no acknowledgement of other variables that could have influenced their longevity. In my opinion his thinking is sloppy.
The most exciting compounds available right now are rapamycin and senolytics, including fisetin, dasatinib, and quercetin. These may actually slow or reverse signs of aging. Rapamycin consistently extends lifespan in animal studies even when started in mid or late life. I've been trying to get my father to start on it with Dr. Alan Green who prescribes it via telemedicine.
Peter Attia doesn't have a book but he is a better source of information in my opinion if the topic interests you.
Home - Peter Attia
OPTIMIZE YOUR HEALTH AND LONGEVITY Begin your journey by selecting a topic #1 New York Times Bestseller Outlive: The Science & â¨Art of Longevity Wouldnât you like to live longer? And better? In this operating manual â¨for longevity, Dr. Peter Attia draws on the latest science to deliver...
peterattiamd.com
Back to Sinclair, listen to him talk for five minutes about TRT and why he thinks it will shorten our lifespans in this podcast:
The basis for his opinion is purely theoretical: factors that suppress growth and reproduction generally extend life (IGF-1 knockout, mTOR inhibition, calorie restriction). Testosterone supports tissue growth and reproduction so it must shorten lifespan.
Two of the very best predictors of how much time you have left are your grip strength and walking speed. What effect do you think testosterone will have on those parameters?
The only facts cited to support his position are that eunuchs have been observed to live longer than intact males. There is no acknowledgement of other variables that could have influenced their longevity. In my opinion his thinking is sloppy.
Belekas
nobody
Grip strength and walking speed?I was a moderator of a longevity forum for many years, called the Immortality Institute in the early days and now Longecity.org. That gave me a front row seat to the rise and fall of resveratrol and Sinclair's fall from grace along with it. Somehow, he has managed to rebrand himself as the public face of anti-aging science after writing a very popular book, Lifespan: Why We Age and Why We Don't Have To.
The most exciting compounds available right now are rapamycin and senolytics, including fisetin, dasatinib, and quercetin. These may actually slow or reverse signs of aging. Rapamycin consistently extends lifespan in animal studies even when started in mid or late life. I've been trying to get my father to start on it with Dr. Alan Green who prescribes it via telemedicine.
Peter Attia doesn't have a book but he is a better source of information in my opinion if the topic interests you.
Home - Peter Attia
OPTIMIZE YOUR HEALTH AND LONGEVITY Begin your journey by selecting a topic #1 New York Times Bestseller Outlive: The Science & â¨Art of Longevity Wouldnât you like to live longer? And better? In this operating manual â¨for longevity, Dr. Peter Attia draws on the latest science to deliver...
Back to Sinclair, listen to him talk for five minutes about TRT and why he thinks it will shorten our lifespans in this podcast:
The basis for his opinion is purely theoretical: factors that suppress growth and reproduction generally extend life (IGF-1 knockout, mTOR inhibition, calorie restriction). Testosterone supports tissue growth and reproduction so it must shorten lifespan.
Two of the very best predictors of how much time you have left are your grip strength and walking speed. What effect do you think testosterone will have on those parameters?
The only facts cited to support his position are that eunuchs have been observed to live longer than intact males. There is no acknowledgement of other variables that could have influenced their longevity. In my opinion his thinking is sloppy.
Thank you everyone for the responses. I may not have looked into this enough but on the surface he doesn’t seem to be pushing any specific plans or supplements etc. His podcasts are supported by some sponsors which they acknowledge and thank during the podcasts. Athletic Greens being one. I guess if he is selling off his research or technology to big companies that could raise some eyebrows.
The one question for me about the fasting is whether the body adapts over time to that one meal a day and comes to accept that as the new norm. So it doesn’t perceive that as a physically stressful state but accepts it as everything is ok. Maybe that’s not how it works. He does say somewhere that their research is showing that simply restricting calories while eating 3 meals a day doesn’t have that same affect. It has to be combined with a large period of fasting at least according to their research.
It will be interesting to see what else comes out of this.
The one question for me about the fasting is whether the body adapts over time to that one meal a day and comes to accept that as the new norm. So it doesn’t perceive that as a physically stressful state but accepts it as everything is ok. Maybe that’s not how it works. He does say somewhere that their research is showing that simply restricting calories while eating 3 meals a day doesn’t have that same affect. It has to be combined with a large period of fasting at least according to their research.
It will be interesting to see what else comes out of this.
lunchbeast
Member
I would not go so far as to say 'debunked', but Dr Stanfield has raised serious questions that Dr Sinclair has so far dodged. It might be because he's embarrassed by Dr Stanfield's questions, or he might simply look at Dr Stanfield as an attention-hunting newbie. Either way, I really feel Dr Stanfield's questions have merit and I do wish Dr Sinclair would respond in a credible manner. Dr Stanfield invited him to sit down face-to-face to discuss the concerns, but that went nowhere. I'm not writing off either one - Dr Sinclair, even if resveratrol does turn out to a big nothing, has made amazing discoveries and advancements in our understanding of aging, and Dr Stanfield does an outstanding job of breaking down complex studies into layman's turns so people like me can understand them. Following both closely.
lunchbeast
Member
One more thing. Based on current evidence, being big and strong appears to conflict with living a long time, mostly due to the calories and food required to attain and maintain that strength and size, which conflicts with the fasting requirements Dr Sinclair (and many others) promote. Think about it - does Dr Sinclair look like he lifts?
Happened to find this article which mentions a dizzying number of connections to companies and labs and universities.
KHN article
Hard to tell what this all means.
@lunchbeast - You’re right, he‘s probably not trying to bulk up. One podcast he mentioned weighing around 150+ lbs when he started the fasting a few years ago. Now I think he mentioned being in the 130+ lbs
KHN article
Hard to tell what this all means.
@lunchbeast - You’re right, he‘s probably not trying to bulk up. One podcast he mentioned weighing around 150+ lbs when he started the fasting a few years ago. Now I think he mentioned being in the 130+ lbs
Hyrulewarrior1978
Active Member
I think you’re either one type of person or the other. Do you want to focus on being muscular and eating surplus calories and be on trt or do you want to take rapamycin and live longer with potentially longer healthspan/lifespan. For those who have kids maybe the latter would be the better choice. I don’t think being on trt and taking rapamycin makes sense.
Does it have to be one or the other? Why can't you do TRT and Rapamycin, and get the best of both worlds?
FunkOdyssey
Seeker of Wisdom
Grip strength, gait speed, chair stand test -- these basic physical function tests are the biomarkers that rule them all. They predict everything from depression, cognition, surgery recovery, CHD risk, cancer risk, dementia risk, and most importantly all-cause mortality. Here's a good free text review: Grip Strength: An Indispensable Biomarker For Older Adults - PubMed
Here's a typical study associating grip strength with all-cause mortality:
Associations of handgrip strength with all-cause and cancer mortality in older adults: a prospective cohort study in 28 countries - PubMed
these results indicate an inverse dose-response association between incremental levels of handgrip and all-cause mortality in older adults up to 42 kg for men and 25 kg for women, and a full linear association for participants aged 65 years or over. These findings warrant preventive strategies...
pubmed.ncbi.nlm.nih.gov
The literature on this is overwhelming to the point that I don't even know where to start to present some interesting findings. I searched "gait speed mortality" on pubmed and it returned over 900 results: gait speed mortality - Search Results - PubMed
So this is where I think the research anti-aging scientists are doing in lower life forms may not directly translate to human longevity. If you restrict calories and protein and avoid anything anabolic you might reduce your cellular rate of aging and then become so frail, sarcopenic and osteoporotic that you die anyway from a simple fall.
I would like to pursue the hybrid approach and I don't see why you wouldn't. Look at Peter Attia, he talks often about how he is training for the "centenarian olympics" and is very concerned with carrying enough muscle mass into old age to maintain his mobility and physical function, while using time-restricted feeding, periodic fasting, and a weekly dose of rapamycin to slow his aging. I suppose professional bodybuilding is incompatible with longevity but there's no reason you can't be both athletic and long-lived.
Testosterone probably has a mixture of dose-dependent positive and negative effects on longevity, and the net effect doesn't seem obvious to me. Contrast with growth hormone: GH and IGF-1 are without question having a strong negative impact on lifespan at increasing levels. That's definitely one to avoid if you are concerned.
Hyrulewarrior1978
Active Member
Correct me if I’m wrong, but I don’t think Peter attia is on trt. None of those longevity doctors and scientists are. Even Huberman mentioned stopping trt after one year. Also i mean trt does increase gh and igf-1 and also shortens telomeres. I would also like to add that rapamycin only increased mouse lifespan by 15 percent so I’m assuming it’s lower in humans. So not sure if risks outweigh benefits of taking it. Peter doses it at 8-10 mg weekly and complains constantly of getting mouth ulcers.
FunkOdyssey
Seeker of Wisdom
I don't think they are on TRT but why would they be if they weren't hypogonadal? Did Huberman explain why he stopped? As far as I know, the only reason he started was to develop some firsthand experience for a book he is writing on hormone optimization.
To the extent that TRT increases GH and IGF-1, that would be a negative effect among a mix of positive and negative effects of TRT on longevity. And what makes you think TRT shortens telomeres in human men? Some researchers are suggesting testosterone supplementation for the express purpose of lengthening telomeres:
Epidemiological and Mendelian Randomization Studies of Dihydrotestosterone and Estradiol and Leukocyte Telomere Length in Men
AbstractContext:. Advancing age is accompanied by an accumulation of ill health and shortening of chromosomal telomeres signifying biological aging. T is m
academic.oup.com
The effects on mouse lifespan are variable but always positive and in some cases very impressive:
Effect of rapamycin on aging and age-related diseases—past and future - GeroScience
In 2009, rapamycin was reported to increase the lifespan of mice when implemented later in life. This observation resulted in a sea-change in how researchers viewed aging. This was the first evidence that a pharmacological agent could have an impact on aging when administered later in life...
link.springer.com
Peter pushes the envelope of rapamycin dosing and that's why he has the mouth ulcers. I experimented with it at 5 mg weekly and had no trouble with that, although it did make my thumb twitch. It's like TRT or anything else where you can titrate dose to prevent side effects.
Hyrulewarrior1978
Active Member
Yea I mean huberman gave that response and I was like what? Not sure i believe that’s the reason. But he’s buddy buddy with all those longevity experts and doctors so who knows? And what’s your definition of hypogonadal because every doctor has their own definition of what that is apparently. T does shorten telomeres I have to find the pubmed article.I don't think they are on TRT but why would they be if they weren't hypogonadal? Did Huberman explain why he stopped? As far as I know, the only reason he started was to develop some firsthand experience for a book he is writing on hormone optimization.
To the extent that TRT increases GH and IGF-1, that would be a negative effect among a mix of positive and negative effects of TRT on longevity. And what makes you think TRT shortens telomeres in human men? Some researchers are suggesting testosterone supplementation for the express purpose of lengthening telomeres:
Epidemiological and Mendelian Randomization Studies of Dihydrotestosterone and Estradiol and Leukocyte Telomere Length in Men
AbstractContext:. Advancing age is accompanied by an accumulation of ill health and shortening of chromosomal telomeres signifying biological aging. T is m
The effects on mouse lifespan are variable but always positive and in some cases very impressive:
View attachment 24563Effect of rapamycin on aging and age-related diseases—past and future - GeroScience
In 2009, rapamycin was reported to increase the lifespan of mice when implemented later in life. This observation resulted in a sea-change in how researchers viewed aging. This was the first evidence that a pharmacological agent could have an impact on aging when administered later in life...
Peter pushes the envelope of rapamycin dosing and that's why he has the mouth ulcers. I experimented with it at 5 mg weekly and had no trouble with that, although it did make my thumb twitch. It's like TRT or anything else where you can titrate dose to prevent side
Hyrulewarrior1978
Active Member
Experimentally elevated testosterone shortens telomeres across years in a free-living songbird - PubMed
Reproductive investment often comes at a cost to longevity, but the mechanisms that underlie these long-term effects are not well understood. In male vertebrates, elevated testosterone has been shown to increase reproductive success, but simultaneously to decrease survival. One factor that may...
pubmed.ncbi.nlm.nih.gov
FunkOdyssey
Seeker of Wisdom
I saw that study but it isn't clear that the free-living songbird is a good proxy for us on TRT, if higher DHT and E2 in men correlates with longer telomeres. Every human study I find on this topic is showing that either T or its metabolites DHT and E2 are associated with longer telomere length.
pubmed.ncbi.nlm.nih.gov
onlinelibrary.wiley.com
Don't tell Danny higher E2 lengthens telomeres or we'll never hear the end of it.
Relation between sex hormones and leucocyte telomere length in men with idiopathic pulmonary fibrosis - PubMed
Plasma testosterone is associated with LTL independent of age or rare protein-altering variants of telomerase. No genetic variations of androgen-related pathway genes are associated with androgen concentrations. Further studies are warranted to examine whether hormonal interventions might retard...
pubmed.ncbi.nlm.nih.gov
Error - Cookies Turned Off
Don't tell Danny higher E2 lengthens telomeres or we'll never hear the end of it.
FunkOdyssey
Seeker of Wisdom
The results of a very large prospective study (150k men) on the relationship between testosterone level and mortality that also cites many previous studies in the discussion:
pubmed.ncbi.nlm.nih.gov
The relationships between testosterone and various types of mortality are always either inverse or neutral. There's no sign here that testosterone is a longevity-reducing hormone (in the physiological range).
Serum Testosterone is Inversely and Sex Hormone-binding Globulin is Directly Associated with All-cause Mortality in Men - PubMed
Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related, and cancer-related mortality. Confirmation and determination of...
pubmed.ncbi.nlm.nih.gov
The relationships between testosterone and various types of mortality are always either inverse or neutral. There's no sign here that testosterone is a longevity-reducing hormone (in the physiological range).
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