Get hungry, out of breath and a little cold.

Do that each day and you’re likely to have a lot more healthy days and a longer life.

That’s the advice of a doctor who lives by his own advice. But he’s not your local practitioner. If science had rockstars, this guy would have a one word name, like Bono or Sting.

Instead we know him as Dr. David Sinclair — Professor of Genetics at Harvard Medical School & Author of “Lifespan: Why We Age- And Why We Don't Have To.”

As a professor, scientist and researcher, Dr. Sinclair doesn’t prescribe methods for individuals or recommend any products by brand but he is assiduously testing NMN (he’s perhaps the world’s most vocal proponent of this Vitamin B3 derived molecule) which is showing jaw-dropping results in age-reversing, longevity and lifespan testing.

Dr. Sinclair recently logged on to Reddit for an AMA (Ask Me Anything) session open to the public. For over four hours he sparred, informed and urged us to alter our behavior and eating habits to do a few basic things, including dietary supplementation, that he’s finding will add years of healthy living to our lives.

After poring over every question and every answer, we’ve distilled and abridged the AMA session to these highlights, which are sometimes edited for clarity. You are also welcome to review the Reddit post here.

Here’s Dr. Sinclair’s introduction:

Hi there, this is David Sinclair. I'm a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. I spend most of my waking hours working to better understand why we age and how to slow the effects of aging.

I'm happy to answer questions on any topic. Recent discoveries, NMN/NR, resveratrol, fasting/CR, the future, my book Lifespan: Why We Age- And Why We Don't Have, favorite movies…

To keep up on what I'm doing, here are my social media accounts:
Twitter
Instagram

I also have a newsletter that shares updates on current research and other things I'm paying attention to. That can be found on my website here.

Please remember that the responses here should not be taken as medical advice. Consult with your physician for medical needs. I’m a PhD, not a MD.

Q: Is there even a timeline currently or are the mechanisms of aging proving too difficult for current research to crack?
A: Nothing's too difficult. We are a small group of scientists. If we put as much effort and money into aging as we do luxury goods, we'd have it solved.

Q: Would you be kind and briefly summarize at what point we are in the process of research? What is the main focus? What are the recent discoveries? Where would we be in the next 5 years?
A: We are at the same stage as the Wright Brothers. We've built a glider that works well. We have engines were strapping on. We know it’s possible. We have seen birds fly. The main focus is finding ways to turn on longevity genes, what is the effect of combining them, how to delete senescent cells, and epigenetic reprogramming. Next 5 years I hope to see medicines available based on this research. Hard to know what will be first. I hope to have reversed aging in the eye to restore vision.

Q: What assurances do we have that anti-aging technology will work across the entire body and organ systems? What if you have a 95 year old who, because he uses anti-aging technologies has the cardiovascular system of a 40 year old, but he still has the joints and bones of a 95 year old? Do anti-aging technologies work across all organ systems?
A: So far these treatments benefit the entire body of animals. They probably wouldn’t extend health and lifespan otherwise.

Q: What particular things do you think will be bottlenecks in the practical application of longevity research?
A: Main impediment is that aging is not something doctors are inclined to treat. Why? Because aging is not yet defined as a disease or even an ailment by regulators, even though it's the main cause of disability and disease. It's considered “natural." If this were to change, and aging was defined formally as a medical condition (as suggested by the WHO), then doctors could more easily feel comfortable prescribing medicines that slow aging to people over a certain biological age, instead of waiting until it's too late. Other things to do are to educate doctors, do research in this area, help increase funding of aging research and development. Getting the word out is a good start. Thanks to everyone who has made it a topic of discussion among friends and colleagues.

Q: On the topic of supplementation – would you consider it to be wise for someone to start in their mid-twenties?
A: I started eating well in my 20s.I started Resveratrol in my early 30s (as soon as we discovered it activates SIRT1). NMN and metformin in my 40s. No desserts after 40. More serious intermittent fasting as much as I can in my 50s. It's a risk-reward calculation. Would I take metformin and NMN in my mid-20's. Hard to say. I'd focus on the other things first – IF, gym, sleep because I don't think it's necessary if you can do all the other things.

Q: How many years would you reasonably expect a person take NMN and resveratrol to add to their life? Are these supplements in the range of 1-10 years of added life/health span or more?
A: It's somewhere between 0 and 10 years. Increased healthspan is also something to consider. That is a possible side-effect.
Consider: these lifestyle changes prevent cancer or a heart attack at 65, then they could have a big effect for that individual. My father is still going strong @80.

Q: You mentioned on the mindbodygreen podcast that you were able to bring your age down from 10 years older than you were at the time to a significantly younger age. What is the protocol or the things/steps you implemented? How can regular people measure their age?
A: Well, it's not a perfect test of age, of course, it's an indicator that I was doing the right things…What I did to improve my bloods over those months was to start on NMN and metformin (which suppresses my appetite). It worked so I kept doing it. Test, change, retest. That's what I do. The two tests are InnerAge from InsideTracker (the one I did) and the other is the epigenetic clock (which I hope to do soon). *disclosure: I have invested in InsideTracker and am an unpaid advisor.

Q: How do you cycle NMN and Resveratrol during the week?
A: I take NMN daily in the AM. Resveratrol also in the AM in my small bit of home made yogurt. Metformin daily 500mg in AM then PM (considered a medium dose) unless I work out, then I skip metformin. More info on page 303 of my book and in Part 2, if you'd like.

Q: why 1000mg of NMN and Resveratrol?
A: That's the dose that seems to work for my bloodwork. Clinical trials indicate I need 1g to improve insulin sensitivity.

Q: Why combine Resveratrol with NMN (or other NAD boosters)?
A: Accelerator pedal plus fuel.

Q: I wanted to ask if you have a preference, and why, between consuming Resveratrol vs pterostilbene? I read that you take 1 gram of resveratrol per day with yogurt but that pterostilbene is more bioavailable.
A: There is a lot more data on Resveratrol. Positive results in humans. I'm data -driven.
https://www.ncbi.nlm.nih.gov/pubmed/25137036
https://www.ncbi.nlm.nih.gov/pubmed/24695890

Q: If you wouldn’t have access to Metformin would you be using berberine (or berberine/curcumine combo) instead?
A: Likely berberine. I've predisposition to diabetes in family history and in my genes. We've shown Berberine to be an effective mitochondrial enhancer and it looks effective in human trials I’ve read.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366688/

Q: Recently, I've given my grandparents to try NMN/Resveratrol (0.75g/day) for 20ish days test period and there weren't any visible differences. Do you have any observation on what and when there could be visible results?
A: In mice we don’t see visible differences in such a short amount of time. The effects seen in mice are mostly a slowing of frailty over time, with delays of CVD, inflammation, and increases in endurance. Possible effects of resveratrol based on previous human studies might be lowering of blood pressure, insulin, and inflammation. Anecdotally, some people report more energy, alertness and better sleep, which is at least consistent with mouse data, albeit anecdotal.

Q: Why does NMN reportedly have an energy boosting effect? Wouldn’t the benefit of DNA repair be felt a lot more gradually?
A: The energy-boosting is thought to mostly be from an increase in the number and activity of mitochondria (ie. the power packs of cells) that make chemical energy in the form of ATP.

Q: How are NAD levels measured in an animal? If it’s blood, please be specific about how exactly it is detected in the blood, if possible.
A: We measure NAD in blood and tissue. In humans, blood. There are a few ways to do it. Fluoresent assays and liquid chromatography are the most convenient. Mass Spec is another level up. We use Mass Spec in our Cell 2007 paper but its not easy.

Q: Last year I was diagnosed with Chondromalacia patella at age 26, a thinning of the cartilidge under the kneecap. My orthopedist essentially told me all I can do now is lessen further damage, but that I can't grow new cartridge, and will have this for the rest of my life. Could it ever be possible to slow or even reverse the damage done to my knee with the drugs/supplements you see coming in the future? My second question is: one of the common signs we see of aging (and one I'm starting to see myself) is hair thinning or hair loss. Is this an area that could be addressed or dealt with through engaging our longevity genes?
A: I'm becoming very interested in regeneration and hope to be testing our ability to fix cartilage or joints. We tried NMN on mouse joints and didn't see a benefit. Perhaps our new reprogramming tech will help.
Every sign of aging should be addressable by engaging longevity genes. That would include hair. Why? Rodents that are calorically restricted (CR) aren’t just healthier, they have less grey hair and less hair loss, and longevity genes are mediators of CR's effects. 🙂

Q: With intermittent fasting, is there a minimum fasting period necessary to see metabolic health benefits? I know some people do the 16:8 method, but what is the minimum fasting period necessary to benefit from IF?
A: It’s not known but if I were to make an educated guess, you need to do more than skip breakfast, because people have always done that and we don’t see them all living >100. I try to skip breakfast AND lunch. It's hard. I often fail. But I don’t give up.

Q: I think its widely accepted that dietary intervention is currently the best and safest method of extending health-span in humans. Would you agree? Is it likely that the health benefits of pharmaceutical interventions will surpass that of dietary interventions in the next few decades?
A: Don’t eat 3 meals a day + snacks is the best advice I can give. I expect drugs to beat IF, and remember an elderly or sick person cant be expected to fast (or run a few miles a day).

Q: Do you see the field of aging research converging toward a unified theory of aging? I notice a lot of similarity between your information theory of aging and the somatic restriction theory proposed by Dr. Michael West, for example.
A: Exactly. Michael and I recently spent an afternoon together brainstorming. It does feel like we are making progress.

Q: Do you have an opinion on Curcumin? Based on the Life Extension Magazine, they say that it reduces low-grade inflammation, increases the activity of sirtuins, decreases the activity of mTOR, enhances AMPK, boosts autophagy, etc. Sounds like it would be really useful to add to the regimen.
A: It's an interesting molecule from turmeric/tumeric. Raises SIRT1 protein levels (not apparently a direct activator). Activates FOXO pathway. Holds a lot of promise.

Q: Could you please elaborate on your workout routine? Is it more or less the same thing as what your father does, or does he do something different?
A: Each Sunday its up to 2 hours of hip-hinge, dead-lifts, benching, lats, bicep, triceps, chin ups, seated row, leg presses etc. Its very similar to my Dad's workout, but he does rowing too. In fact he and I have been working out together the last 3 weeks. Then 30 min of stretching and aerobics (my least favorite). Best HIIT exercise for me – sled push x 5. Pulse goes to 170. You can do this on some treadmills. Im lucky to have an amazing trainer who is very scientific about it. I do extra lifts at home during the week if Im home. Ben, our son, is almost as strong as me at 11 and my Dad at 80 is stronger 🙁

Q: Any negative symptoms or side effects from NR/NMN supplementation that you've seen or heard of in animal models or humans?
A: We haven't seen any. NMN does grow new blood vessels (in muscle), which is something to keep an eye on vis a vis cancer. There is a study from Wash U showing lowing NAD in cells slows the growth of cancer cells, which was interpreted by some as showing NAD causes cancer. This isn’t the correct interpretation of the data. In mice, we've seen protection from breast cancer growth.

Q: Do you think there is a significant difference in sublingual vs oral administration of NMN?
A: I've not seen a head-to-head comparison. Don't know if there's an advantage to one or another. We all need to be data-driven. Someone should publish a study if they've done one. I can tell you that oral NMN can raise NAD levels in the bloodstream of mice and people.

Q: Would you please comment on ways to protect Telomeres?
A: People who have consistently high levels of physical activity have significantly longer telomeres than those who have sedentary lifestyles. Get moving.  https://www.cell.com/fulltext/S0092-8674(07)00973-7

Q: Can you comment on the potential of aging research to be self-serving and take resources away from research on childhood disorders – particularly since these latter disorders are underfunded to begin with and they lack representation in legislative bodies that fund research? How do we maintain parity and equity in healthcare related research?
A: Great point. We spend $300B on coffee in the USA each year. There should be more money to cure diseases so there isn't a fight about whose ailment is more important. The good news is that aging research should also help childhood diseases and rare diseases, too. Aging research is all about finding and activating the body's defenses against diseases and deterioration. Reprogramming might fix eye and ear defects. MetroBiotech, a company I co-founded, is working to treat a rare disease called Freidrich's ataxia that affects the young.

Q: Are onions a superfood because they taste so vile and cause physical pain?
A: They are a superfood because onions have high concentrations of allyl sulfides, calcium, folate, vitamin C, quercetin (and lesser amounts of isorhamnetin and anthocyanins). Quercetin is a direct SIRT1 activator and a part of the combo that kills senescent cells. Not because they cause physical pain (though activating heat TRP receptors is thought to be healthy also).

Q: That we know of, is there a point at which hormesis is not as beneficial? I don’t mean overdoing one thing constantly, but a combination of things…being slightly cold most of the day, fasting, exercising, eating stressed plants, etc. Is there evidence of a balance somewhere…to where total comfort and sanity contributes to the effect or is adapting to consistent misery key? And once a regular practice of hormesis is attained, is there a need to increase it to new levels to grow stronger, as we do in exercise performance?
A: This is the main topic of discussions at conferences on aging. We've made breakthru's figuring out single treatments/interventions – and now we are trying combos. It will take time to know the answers. The key seems to be to pulse things. Don't always be hungry or work out. Do something hormetic, then switch it up. Fast then eat…run and lift weights, then rest.

What I do while we wait for that data is try combinations and see if my body reacts ok. If I don't feel right or my bloodwork doesn't look good, then I have a good idea that it was too much. So far, I haven't found that doing all the things on page 303 is too much. I feel great, my bloodwork is great, heart rate great, and haven’t been sick in years. Not even a sniffle.

Q: Got your book when it was first released. Mind blowing stuff. Is there a long lead time for NMN to produce any results? What are the latest developments on human trials of NMN?
A: I didn’t feel different in my 30s. I’m now 50 with no grey hair or hair loss or any ailment. Bloodwork excellent. Haven't had a cold in years. My Dad's 80 and feeling in perfect health (though he lost his hair at 30!). This isn’t proof anything works, but the point is don’t expect to suddenly be young. Anecdotally in people, and in mice, NMN may improve energy and sleep in short-term. I’m working with a team to test an NAD booster in human clinical trials now.

Q: Have you ever undergone any cosmetic enhancement such as botox, liposuction, or dyeing hair?
A: No. I wish. I did find a grey hair last year and ripped it out.

Q: Does the Resveratrol/NMN regime prevent physical aging? I noticed since you started this regime, you aged quite fast in terms of physical appearance.
A: Must be all the time spent on my computer answering questions instead of exercising 🙂

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This article is for informational purposes only, even if and regardless of whether it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of RenovoVita.