Anti-aging Doc, David Sinclair Tells Joe Rogan About His Groundbreaking NMN Supplement Research

NMN supplement review

Dr. David Sinclair explains to Joe Rogan why his NMN supplement research convinced him and his family to take NMN, as well as resveratrol and metformin. Watch, listen and read.

NMN supplement review

Harvard geneticist Dr. David Sinclair is perhaps the most famous anti-aging researcher on the planet, largely due to his NMN supplement research. In the video and audio files below, Dr. Sinclair tells podcaster extraordinaire, comedian and mixed martial arts commentator Joe Rogan about the science behind why he and his family supplements daily with a widely available supplement called NMN.

If you have two-plus hours to spare and are interested in ground-breaking anti-aging research that’s ratcheted down in layman’s terms, go take a listen or watch.

Or simply scroll down and read my written review. Either way, you’re about to get an explosion of information that could help you live a longer, stronger life.

 

Here’s what’s in this post:

  • Joe Rogan interviews Dr. Peter Attia, shown in both audio and video formats
  • Who is Dr. David Sinclair?
  • Dr. Sinclair’s Information Theory of Aging (the first unifying theory of aging)
  • Is it possible to reverse aging? (His NMN supplement research on mice says “Yes”)
  • Why Dr. Sinclair supplements with NMN, resveratrol and metformin
  • Dr. Sinclair’s health habits
  • Other health topics he discussed with Joe Rogan

Let’s dig in…

 

 

Who is Dr. David Sinclair?

David Sinclair is a Professor in the Department of Genetics at Harvard Medical School. He runs two labs devoted to longevity research: one at Harvard and the other in his native Australia. His new book, which I’m presently reading, is called, Lifespan: Why We Age and Why We Don’t Have To.

Click here for a rundown of all his awards

David Sinclair obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney in 1995. A chance meeting with Dr. Leonard Guarente lead to a posting as a postdoctoral researcher at M.I.T. with Dr. Guarente as his advisor. There he co-discovered a cause of aging for yeast, as well as the role of sirtuin2 in epigenetic changes driven by genome instability. (I’ll speak about sirtuins in a bit.)

If Dr. Guarente sounds familiar to you, it may be because he’s the founder of Elysium Health, the maker of the NAD+ activator, Basis (similar to Tru Niagin), which contains NR (Nicotinamide Riboside) and pterostilbene, a stilbenoid chemically related to resveratrol. I’ve been taking Basis for two years and first wrote about it in an article entitled, Can Elysium’s “Basis” Pill Really Make You Younger?

In 1999, David. Sinclair was recruited to Harvard Medical School where his laboratory’s research has focused primarily on understanding the role of sirtuins in disease and aging, with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration and cancer. He has also contributed to the understanding of how sirtuins are modulated by endogenous molecules and pharmacological agents such as resveratrol.

Dr. Sinclair is co-founder of several biotechnology companies (Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, Liberty Biosecurity) and is on the boards of several others. He is also co-founder and co-chief editor of the journal Aging. His work is featured in five books, two documentary movies, 60 Minutes, Morgan Freeman’s “Through the Wormhole” and other media. He is an inventor on 35 patents and has received more than 25 awards and honors including the CSL Prize, The Australian Commonwealth Prize, Thompson Prize, Helen Hay Whitney Postdoctoral Award, Charles Hood Fellowship, Leukemia Society Fellowship, Ludwig Scholarship, Harvard-Armenise Fellowship, American Association for Aging Research Fellowship, Nathan Shock Award from the National Institutes of Health, Ellison Medical Foundation Junior and Senior Scholar Awards, Merck Prize, Genzyme Outstanding Achievement in Biomedical Science Award, Bio-Innovator Award, David Murdock-Dole Lectureship, Fisher Honorary Lectureship, Les Lazarus Lectureship, Australian Medical Research Medal, The Frontiers in Aging and Regeneration Award, Top 100 Australian Innovators, and TIME magazine’s list of the “100 most influential people in the world”.

 

The book summarizes much of his research and presents his unique unified theory of aging, which he calls the “Information Theory of Aging“. If this theory proves to be true, it will be the first that explains the single cause of aging; that which is behind the widely accepted nine Hallmarks of Aging:

  1. Genomic instability (DNA damage)
  2. Telomere attrition (chromosome “caps” become less protective)
  3. Epigenetic alterations (gene expression becomes compromised)
  4. Loss of proteostasis (proteins are damaged)
  5. Deregulated nutrient sensing (imbalanced metabolism)
  6. Mitochondrial dysfunction (faltering energy)
  7. Cellular senescence (zombie cells)
  8. Stem cell exhaustion (tissues no longer get repaired)
  9. Altered cellular communication (cell “communication” is compromised)

(For more on the Hallmarks of Aging, see my article about it.)

 

Dr. Sinclair’s Information Theory of Aging

To describe his Information Theory of Aging, Dr. Sinclair uses the analogy of digital and analog systems that store and transfer data (information) and declares that the fundamental cause of aging is a loss of cellular information that degrades over time.

Our genome (genetic code) is digital and thereby easy to preserve and replicate, Sinclair explains, as it’s “written” in a linear sequence of four letters corresponding to two nitrogen-containing compounds: Purines (consisting of A and G, or adenine and guanine), and Pyrimidines (consisting of C and T, or cytosine and thymine). The genome stays very much intact as we age.

Our epigenome is analog. The other part of the “information” we inherit from our parents is epigenetic information. Epigenetics is the study of changes in organisms, like us, caused by modification of gene expression rather than alteration of the genetic code itself. This pattern of gene expression speaks to which genes are turned on, and when.

Each cell turns on only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation, which plays a critical part of normal development. Genes are turned on and off in different patterns during development to make brain cells look and act different from liver cells or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments.

(There’s much more to Sinclair’s Information Theory of Aging. If interested, read the article about it I wrote for ProHealth Longevity.)

 

Does NMN Supplement Research Show It’s Possible To Reverse Aging?

Various of studies have reversed aging in several animal models; namely, yeast, worms, fruit flies, mice and monkeys. Humans are much harder to study. We’re long-lived and don’t take kindly to alteration, whether it be or biology or environment. But what can be measured in humans is how our biometrics respond to various potential anti-aging interventions.

For instance, various forms of caloric restriction (complete fasting, intermittent fasting and fasting mimics, such as the ProLon Fasting Mimicking Diet, have improved various biometrics associated with human longevity, such as lower blood pressure, lower fasting blood sugar, less coronary artery disease, less chronic inflammation, etc. Moreover — and central to Dr. Sinclair’s work — caloric restriction and its mimics activate sirtuins, a family of proteins that play a role in aging by regulating cellular health.

Although it only involved nine people, a 2019 study conclusively showed that a combination of metformin, DHEA, and human growth hormone resulted in a decrease of two years of the subjects biological age. A reduction of a protein called C38 also occurred. C38 resides in immune cells and increases in quantity as we age. This is unfortunate, because C38 is the main enzyme in our body that degrades NAD+, a conezyme required for sirtuins to properly function. The older we get, the less NAD+ or body produces.

NAD+ levels decline over time

Much of Dr. Sinclair’s research work (and that of his mentor and post doctoral advisor, Dr. Lenny Guarantee) is focused on the role that sirtuins have in how we age and how to support their function. (As you’ll soon see, this led Dr. Sinclair to his NMN supplement research.)

Sirtuins, nicknamed “the longevity genes”, are a family of protein enzymes involved in regulating cellular processes, including the aging and death of cells and their resistance to stress. They remove acetyl tags from histones and other proteins and, by doing so, change the packaging of the DNA, turning genes off and on when needed. These critical epigenetic regulators sit at the very top of cellular control systems, controlling our reproduction and our DNA repair.

DNA breaks in chromosomes distract the sirtuin complex resulting in genes that inappropriately get turned on. You may recall from your high school biology that chromosomes are threadlike structures of nucleic acids and protein found in the nucleus of most living cells. They carry genetic information in the form of genes. Mammals like us have seven sirtuins.

Insults to the genome, such as a double strand break, distract sirtuins from their job of responding to various cellular stresses as they go into gene repair mode. Over the term of, say, an 80-year life, the cumulative damage caused by gene expression (getting turned on) when they should not is a good part of what makes us old.

Simply put: Sirtuins are genes which protect all organisms (like us) from deterioration and disease.

The focus of the research on sirtuins done by Dr. Sinclair and others is to find out how to make them more robust and then see how that affects the aging process. In all the animal models studied, improving sirtuin function extended both health and lifespan, but what about in humans?  We don’t know for sure, but that hasn’t stopped researchers like Sinclair and Guarantee (and myself and thousands of others) to take the supplement compounds that worked so well in animal models.

The reason for this is the convincing results of David Sinclair’s NMN supplement. Such results have lead him, his family, and the rest of us to supplement with resveratrol and NMN (and in my case, NR as well), along with metformin (in his case, not mine as yet).

 

Dr. Sinclair’s NMN Supplement Research and Why He Supplements With NMN, Resveratrol and Metformin

NMN supplement research

NMN boosts sirtuin function

It’s a cause and effect chain of events. The NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) molecules boost NAD+ (nicotinamide adenine dinucleotide), which turn nutrients into energy as a key player in metabolism and works as a helper molecule for proteins that regulate other biological activity; namely, the sirtuins.

So:

↑NMN/NR → ↑NAD+ →  ↑Sirtuins → ↑longevity (in animals, potentially humans too)

Dr. Sinclair takes one gram of NMN powder every morning mixed in yogurt in order to for the fat in the yogurt to improve NMN assimilation. He also takes 500 mgs of resveratrol mixed in the yogurt and an unknown amount of metformin.

His confidence in this NMN molecule comes from the many studies he’s done for his NMN supplement research on various animal models, such as mice. With mice, taking NMN has proven to make them appear more youthful, and “they get the benefit of exercise without having to exercise”, such as increasing the amount of time and distance run.

I have not confirmed the brand of NMN that Dr. Sinclair (and his family) uses, but Rich Carson, the Founder of ProHealth, says it’s sourced from the same manufacturer as ProHealth uses to make its NMN powder and capsules.

Resveratrol stimulates the body’s defense against aging and disease

Resveratrol is a polyphenol that’s well known for its (mild) antioxidant properties. Dr. Sinclair points out to Joe Rogan that, “Antioxidants have been the biggest disappointment in the aging field… Antioxidants have, with very few exceptions, failed to extend the lifespan of any organism.” (Read my piece, If The “Free Radical Theory of Aging Is Dead”, Should You Take Antioxidants?.)

He supplements with resveratrol anyway (as do I), because:

  • “… it really works is it stimulates the body’s defenses against aging and disease”, says Sinclair, by binding to sirutins.
  • His research on mice show that at a human equivalent of 250 mgs/day, the mice become resistant to the negative side effects of consuming a high-fat/Western diet; specifically, their livers, arteries, and metabolic markers mimicked those of healthy, lean, and young mice.

I don’t know what brand of resveratrol that Dr. Sinclair uses, but Life Extension’s Optimized Resveratrol is approved by the independent supplement review company, ConsumerLab.com.

By the way, a similar plant compound, pterostilibene, may be more effective than resveratrol, which is why Dr. Lenny Guarantee blends it with the NR product his company, Elysium Health, makes, called Basis.

Click here to learn more about Pterostilibene

Pterostilbene is a is a stilbenoid (a class of molecules found in plants) chemically related to resveratrol that’s been shown to improve metabolic health in lab studies.

Pterostilibene is similar to resveratrol. Recent studies suggest that Pterostilibene is actually superior to Resveratrol, which might sadden Dr. Sinclair, as he also was one of a team of scientists who discovered that Resveratrol, a molecule in red wine, can “stick to this protein that controls ageing and makes it more active”, he said.

 

Does Metformin decrease physical performance?

Metformin is a drug that’s being re-purposed that I’ve written about. Traditionally used to help diabetics, metformin has become a potential anti-aging drug, and it’s on the fast track for human trials.

Researchers have already proven that the diabetes drug extends the life of animals, and the US Food and Drug Administration has green-lighted a trial to see if the same effects can be replicated in humans.

Here’s some tibits about metformin:

  • Scientists think metformin may be the best candidate for an anti-aging drug because it increases the number of oxygen molecules released into a cell, which appears to boost robustness and longevity.
  • Metformin is safe given that it’s the world’s most widely used diabetes drug.
  • It’s cheap, just six cents per pill.
  • Mice treated with Metformin increased their lifespan by nearly 40% and their bones became stronger.
  • Last year Cardiff University found that when patients with diabetes were given the Metformin lived longer than others without the condition, even though they should have died eight years earlier on average.

That all sounds good, but recently new evidence suggests that there are some metformin side effects that may diminish your hard-earned physical fitness. Dr. Sinclair thinks that metformin may be interfering with our mitochondria (the cells “energy factory”), disrupting its energy production at a time (post exercise) when it (the mitochndria) needs to be amplified. Because of this, Dr. Sinclair only takes metformin on days he does not exercise.

 

Dr. Sinclair’s Health Habits

Dr. Sinclair’s Workout and Eating Routine

He admits that although it’s far from ideal, Sinclair only spends about three hours a week in a gym, and all of those hours are in one day! During that time, he lifts weights for an hour, stretches, and then does some hot/cold therapy (a sauna/cold tub).

He gets hungry at least once a day

Sinclair fasts intermittently as much as he can. For him, that typically means skipping breakfast and eating a late lunch. It’s important that become comfortable experiencing hunger, he says, because sirtuins are activated when you’re hungry due to a rise in NAD+ levels. This is why NAD+ boosters like NMN and NR are considered fasting mimics — they have a similar biological effect as does fasting itself.

He tries to optimize his sleep

Dr. Sinclair gets between six and seven hours of sleep a night, less than most studies suggest is ideal, which for most of us is between seven and nine hours. He also wears an Oura Ring (similar to the less expensive Motiv Ring) to track his sleep. He sometimes takes a small dose of melatonin as well. (Although not said in the podcast/video, a small dose of melatonin is between two and five milligrams. I find the sublingual form works best.)

He stresses that there’s a direct correlation between a lack of sleep and Alzheimer’s disease, and therefore he focuses as best he can given his hectic work and travel schedule to get rejuvenating sleep, which includes wearing blue light blocking glasses a few hours before bed; that, he says, has greatly improved his sleep quality.

 

Other Interesting Topics Discussed by Sinclair and Rogan

What follows are some other interesting topics related to longevity that were covered by Dr. Sinclair and Joe Rogan.

The Horvath Clock is becoming the most reliable way to measure biological age

Biostatistician Steve Horvath can determine chronological age and predict mortality by measuring DNA methylation, a type of epigenetic modification, says Elysium Health. Dr. Sinclair says:

“Using the same 353 locations in DNA, and an identical mathematical algorithm, allows you to measure the age of a person based on DNA from any tissue. I wish I could tell you a good rationale for it. On some level, it is simply a miracle.”

I think, as we use this clock, we’re going to figure out a whole bunch of stuff that we can do to not just slow aging, but reverse it. And not just by 2.5 years. With some of the technology I talk about in my book, I think we could turn the clock back by a decade or more.”

My bioage

Dr. Horvath’s “clock” is behind the math and statistics I used in a Google spreadsheet to determine my own biological age. Get the scoop and test yourself here.
Dr. Sinclair’s 80-year-old Father’s Supplement Protocol

Like Sinclair and the rest of his (adult) family, his 80 year-old father takes NMN, metformin and resveratrol. It’s anecdotal, but his father attributes to his NMN supplementation his ability to regularly exercise vigorously. To showcase his growing prowess, he recently climbed 40 flights of stairs in just 15 minutes, boasts his son, David.

Wear sunscreen and beware x-rays

Why? – Over time, the sun causes DNA damage (it “breaks ” chromosomes) which accelerates aging.  X-rays and airport scanners also do this — going through an airport scanner gives you the same radiation dose you’d get on a five-hour flight. For this reason, it might be a good idea to supplement with NMN (or NR) before and after a flight or getting an x-ray, as Dr. Sinclair’s mice studies show that NMN protects against the effects of radiation.

Consider taking Senolytics

Senolytics are drugs or some natural compounds that kill off senescent cells, which is the phenomenon by which normal cells cease to divide, thereby becoming “senescent”.  As the website Fight Aging describes it, once cells become senescent they pollute surrounding tissue with inflammatory and other signals that evolved for short-term benefit only. When present over the long term, the signals secreted by even a comparatively small number of senescent cells will significantly degrade tissue structure and function, disrupt regeneration, and produce chronic inflammation. This accelerates the development and progression of near all common age-related diseases.

As I wrote in Can New Senoltyic Drugs Delay Aging, researchers from the Mayo Clinic in Rochester, Minnesota aim to move the testing of Senolytic drugs from animal research to human clinical trials. They outlined potential clinical trial scenarios in a paper recently published in the Journal of the American Geriatrics Society.

Said Dr. James Kirkland, director of the Kogod Center on Aging at the Mayo Clinic and lead author of the new paper:

“This is one of the most exciting fields in all of medicine or science at the moment.”

Sinclair says that one study found that by genetically deleting the senescent cells that had accumulated in old mice delayed their aging.

Three over-the-counter supplements that are available now that might vanquish senescent cells are:

  1. Quercetin, a bioflavonoid,
  2. Piperlonguminine, basically pepper, and
  3. Fisetin, a plant polyphenol.

For the latest science on these, read my article, Three Senolytic Drugs Available Now.

 

Your Takeaway

Remember these four things discovered through NMN supplement research:

  1. Sirtuins are genes which protect all organisms studied from deterioration and disease. They need NAD+ to function, which declines dramatically as we age. NMN and NR are two precursors that can boost our body’s production of NAD+
  2. Resveratrol is thought to increase sirtuin activity
  3. Hunger is your friend — try to be hungry often. Sirtuins are activated when you’re hungry due to a rise in NAD+ levels
  4. Wear sunscreen and avoid x-rays/airport scanners. Over time, the sun causes DNA damage which accelerates aging. NMN and NR can be protective.

 

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Joe Garma
 

I help people live with more vitality and strength. I'm a big believer in sustainability, and am a bit nutty about optimizing my diet, supplements, hormones and exercise. To get exclusive Updates, tips and be on your way to a stronger, more youthful body, join my weekly Newsletter. You can also find me on LinkedIn, Twitter and Instagram.

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