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Practical Recommendations from David Sinclair’s Lifespan

Last week, I posted my summary and notes for David Sinclair’s thought-provoking book, Lifespan. In the book, the Harvard professor details his research into aging as a disease. Like any other disease, aging can be prevented, treated, and potentially cured. While Sinclair readily admits that more research and scientific inquiry is needed before we can cure aging—an audacious goal to be sure—there are a number of practical habits and behaviors available today that can forestall the effects of aging. This post highlights those recommendations.

Note that Sinclair is explicit that none of the ideas in his book constitutes health advice or should be substituted in lieu of professional guidance. The following is purely for informational purposes and does not constitute medical advice.

The Basics

Most of the practical recommendations for the book are found in three chapters:

  • Chapter 4: Here Sinclair discusses exercise, diet, cold exposure, and things to avoid (to maintain epigenetic and genetic health).
  • Chapter 5: Here Sinclair discusses molecules (pharmaceuticals and supplements) that mimic or amplify the benefits of health and diet.
  • Conclusion: Here Sinclair presents his personal habits in a short bulleted list.

The underlying cellular biology and metabolic reactions that are promoted by Sinclair’s recommendations are explained in detail in Part I of the book. The core principle is that we want to encourage cellular repair, reduce cellular inflammation, and encourage the recycling of old proteins (autophagy). Activities that promote these beneficial cellular processes are to be encouraged. Those that inhibit or impair these processes should be avoided. Activities like exercise and caloric restriction stimulate cellular survival and repair processes. This type of cellular “stress” (hormesis) is beneficial. It’s the same idea as the old aphorism “that which doesn’t kill you, makes you stronger.”

With that in mind, let’s look at the longevity-promoting actions and behaviors available to us today.

Diet: Eat Less

We might be tired of hearing about diet, but the fundamental role of diet where individual health is concerned is indisputable. Where longevity is concerned, “eat less” is the key recommendation. Studies suggest a strong link between calorie restriction and longevity. Moreover, caloric restriction stimulates many beneficial cellular processes noted above. Caloric restriction is also beneficial as a weight-loss strategy. There are two main approaches for eating less:

  1. Caloric Restriction (CR): Set a daily caloric target below the recommended daily allowance (RDA). Sinclair mentions 25% as a good target. He also cites human studies that show benefits with a 12% caloric reduction. There are different approaches for maintaining a CR diet over time. CR cannot be practiced indefinitely, you’ll need to maintain some level of BMI equilibrium at some point. Some practitioners cycle between CR periods and non-CR periods (e.g. one week on, one week off).
  2. Intermittent Fasting (IF): Practitioners only eat during designated feeding windows. Instead of 3 meals per day, an IF practitioner might eat 2 or only 1 meal per day. For instance, a 16:8 IF schedule means that 16 hours are spent fasting (no food) and 8 hours are spent eating (usually two meals).

Of course, there are a number of other ways one can eat less:

  • The 5:2 diet: Eat 75% fewer calories for two days a week.
  • Eat Stop Eat: Skip food a couple of days a week.
  • Quarterly fasting: Go hungry for an entire week every 3 months (Peter Attia does this).

Per Sinclair: “Almost any periodic fasting diet that does not result in malnutrition is likely to put your longevity genes to work in ways that will result in a longer, healthier life.”

Diet: Eat Healthy

Sinclair doesn’t go into great detail about what to eat, but does touch on some key points:

  • Eat less meat, eat more plants. Diets higher in plant-based foods reduce all-cause mortality.
  • Reduce sugar consumption: evidence suggests high blood sugar increases epigenetic clock.

If in doubt, look to the diets of people who live in “Blue Zones.” These are populations (like Okinawa) where the average lifespan is particularly high. Diet and lifestyle might offer hints to their longevity (genetics is another plausible explanation).



Exercise offers many benefits including increased NAD levels (which activate the survival network). In addition, “longevity regulators like AMPK, mTOR, and sirtuins are all modulated in the right direction by exercise.” Remember: the goal is benign stress.

Here are the book's recommendations:

  • Aim to raise the heart rate and respiratory rate.
  • Higher intensity is better than low intensity.
  • Breathing should be deep and rapid at 70-85% of max heart rate.
  • Should be sweating and unable to speak more than a few words without pausing for breath (aka the hypoxic response).

As for specific exercises, Sinclair mentions:

  • High Intensity Interval Training (HIIT)
  • Running and walking

He doesn’t talk much about weight-lifting, except to say that he does do periodic weight-lifting of his own. Presumably strength, flexibility, and endurance are all desirable physical traits.

Lastly, he mentions two simple fitness tests that use bodyweight exercises (pushup and squat) to measure biological age:

  1. Pushup test: If you are over 45 and can do more than 20 pushups, you are doing well.
  2. Sitting-rising test (SRT): Sit on the floor, barefoot, with legs crossed. Lean forward and in one motion get up to a standing position. Fit people can do this without pushing off with their hands or an intermediate move to their knees. This is effectively a squat.

Cold Temperatures

Exposing your body to uncomfortable temperatures activates longevity genes and “revs up” brown adipose tissue (aka brown fat). Once again, the underlying idea is inducing a tolerable level of stress. Remember: the goal of cold exposure is to induce benign stress NOT to cause hypothermia.

Examples noted in the book:

  • Exercise in the cold.
  • Wear fewer layers.
  • Leave a window open (day and night).
  • Sleep with a light blanket.
  • Turn off the heater.
  • Take cold showers.

It’s worth mentioning that one side effect of calorie restriction is that it reduces the body’s core temperature (bonus).

Sinclair also discusses heat (such as saunas). While he suggests heat therapies may be beneficial, there’s far less scientific research, vis a vis longevity, compared to cold therapies.

Things to Avoid (aka keep your cells healthy)

Recommendations that fall under this umbrella are all about AVOIDING situations that carry risk of increased cellular, genetic, and epigenetic damage. As Sinclair states “we can’t prevent all DNA damage...but we do want to prevent extra damage.”

Specific things to avoid:

  • Cigarettes. “There aren’t many legal vices out there that are worse for your epigenome than the deadly concoction of thousands of chemicals smokers put into their bodies every day.”
  • DNA-damaging chemicals that are part of modern life: pollution, PCBs, plastics, take-out containers.

    • Avoid microwaving plastic containers which releases toxins.
    • Azo dyes (such as aniline yellow) can also damage DNA.
    • Organohalides used in solvents, degreasers, pesticides and hydraulic fluid can damage genomes.
    • N-nitroso compounds are present in foods with sodium nitrite (beers, cured meats and bacon). These are potent carcinogens.
  • Natural and human-inflicted radiation: UV light, X-rays, gamma rays, radon, all damage DNA.

Pills: Drugs and Supplements

Certain molecules are capable of mimicking the benefits of diet and exercise. These are typically available as dietary supplements or controlled substances (prescription medications).


  • Rapamycin (aka Rapamune, Sirolimus)

    • What it does: Immunosuppressant. Inhibits mTor which may benefit longevity.
    • Availability (USA): Controlled substance, prescription needed.
  • Metformin

    • What it does: Used to treat type 2 diabetes. Mimics aspects of calorie restriction.
    • Availability (USA): Controlled substance, prescription needed.
  • Resveratrol

    • What it does: A sirtuan activating compound (STAC) that stimulates sirtuan activity (like DNA repair). Found in red wine.
    • Availability (USA): Available as a supplement.
  • NR (Nicotinamide riboside)

    • What it does: Precursor to NAD (Nicotinamide adenine dinucleotide) which is a STAC.
    • Availability (USA): Available as a supplement.
  • NMN (Nicotinamide mononucleotide)

    • What it does: Precursor to NAD which is a STAC.
    • Availability (USA): Available as a supplement.

While there is some disagreement over the efficacy of NR vs. NMN, both are precursors to NAD. NR is, in fact, converted into NMN. According to Sinclair, “Give an animal a drink with NR or NMN in it, and the levels of NAD in its body go up about 25 percent over the next couple of hours, about the same as if it had been fasting or exercising a great deal.”

Note that supplements are poorly regulated compared to pharmaceuticals. Because of this, extra care must be taken to source supplements from reputable sources. Look for products with the “GMP’ label (Good Manufacturing Practices).

Sinclair’s Regimen

In the concluding chapter of his book, Sinclair shares his personal regimen:

  • Dietary habits:

    • Practices intermittent fasting daily. Usually by skipping breakfast (18:6) and often lunch (20:4).
    • Has increased ratio of plant to meat (but eats meat when exercising).
    • Restricts carbohydrate intake (avoid sugar, bread, pasta).
    • Maintains a BMI between 23-25.
  • Exercise habits:

    • Walks every day (high step count).
    • Exercises at the gym on weekends.
    • Workouts consist of weights and jogging.
  • Cold therapies:

    • Takes ice plunges and spends time in saunas.
    • Keeps ambient temperature cool throughout the day to keep his body on the cool side.
  • Avoids:

    • Does not smoke.
    • Avoids microwaved plastic, UV exposure, X-rays, and CT scans.
  • Pills and supplements:

    • Prescription drug: 1 gram of Metformin per day.
    • Supplement: 1 gram of NMN per day.
    • Supplement: 1 gram of Resveratrol per day.
    • Supplement: Vitamin D, vitamin K2, and 83 mg of aspirin daily.
  • Miscellaneous:

    • Runs quarterly blood panels to track biomarkers and adjust diet and exercise accordingly.

What I Do

I’m no paragon of youth or vitality, but per my most recent routine physical, blood test, and vitals were all good for a middle-aged man. Moreover, I’m happy to say I score well on the physical tests to measure biological age (I regularly do pushup sets of 30-40 reps and can perform the sit-stand test with no problem).

  • Dietary habits:

    • Intermittent fasting 16:8 schedule. My feeding window runs between 12pm and 8pm. I’ve been doing this for the last two months and one and off before that. Given that I’ve never been much of a breakfast person, this is no big sacrifice for me. I may restrict the window further since many days I effectively go 18:6 with no noticeable hunger pangs. The end-goal would be something more strict like a 20:4 schedule, but I’m not there yet.
    • Increased plant:meat ratio. I love meat in all its forms, so this is a challenging habit. When my daughter moved to a vegetarian diet at the start of 2019, I decided to support her and learn to cook more vegetarian dishes. These days, half of my meals are vegetarian. I still like meat and don’t anticipate giving it up entirely, but it is possible to move the needle and still enjoy a burger from time to time.
  • Exercise habits:

    • High daily step count. I aim for 10-12k steps which is made possible by my living in an urban environment where I walk to conduct many of my errands and daily tasks.
    • Cardio exercise: 3-4 times per week. I do a mix of running and HIIT. Usually for 30-60 minutes per session.
    • Resistance exercise: 3 times per week I lift weights (dumbbells or barbells) and/or perform bodyweight exercises. My preference is for the main barbell power lifts: deadlift, back squat, bench press and overhead press. I supplement those lifts with a variety of auxiliary exercises (e.g. rows, Romanian deadlifts, pushups, pull-ups, etc.). My goal is to hit the big muscle groups regularly: back, chest, legs, shoulders. In addition to strength, I believe flexibility and mobility are key: resistance training can help with this.
  • Cold therapies:

    • I keep the thermostat off most of the time which means my home is quite chilly.
  • Avoid:

    • I don’t smoke.
    • I avoid microwaved plastic, UV exposure, X-rays, and the like.

I have yet to try any of the prescription drugs or dietary supplements recommended by Sinclair. Were I to experiment with these, I’d likely try either NMN or resveratrol first.

Further Reading

This is a big topic and this post only considers recommendations from Sinclair’s book Lifespan. Naturally, there are many other scientists and researchers investigating and writing about human longevity. While I cannot claim expertise on this subject, I can point readers to other reliable sources of information—some will augment Sinclair’s ideas and others may contradict him.

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