I recently became aware of two doctors in the field of human longevity (the study of why we age and how to extend healthy lifespan). The first is Dr. David Sinclair, a geneticist at Harvard Medical School. The second is Dr. Valter Longo, a biologist at USC.

Here’s a summary of what I learned. First, from Sinclair:

• Scientists have been able to extend the lifespan and even reverse aging in mice through calorie restriction (fasting) and through giving them certain molecules.

• Fasting has been shown to extend the lifespan of mice, because of something called sirtuin genes. All organisms on the planet have them, including humans. Sirtuins protect against deterioration and disease. When we’re hungry, sirtuins, “send out the troops to defend us,” Sinclair says. “You need a period in the day when you’re hungry. This puts your body in a defensive mode.”

• Sirtuins need a molecule called NAD. Levels of NAD go down with age. For humans, by the time we’re 50 we have approximately half the levels of NAD we had when we were 20.

• Increasing the level of NAD in mice has been shown to extend their lifespan, protect them from disease, and even reverse aging. Researchers increased the NAD levels in mice with a molecule called NMN (a precursor to NAD).

• The results of human trials with NMN aren’t finished yet, but Sinclair has been taking it for years. [A less expensive alternative to NMN is another molecule called Nicotinamide Riboside]. He also takes a Resveratrol supplement. Resveratrol is a molecule that has been shown to make fat mice as healthy as thin mice. Sinclair says it acts as an accelerator for NMN. Resveratrol is like the accelerator pedal for Sirtuins and NMN is the fuel.

• NMN mimics what diet and exercise do (fasting and exercise boost NAD levels), but putting it all together is even better: fasting, healthy food, exercise, NMN, and Resveratrol. When mice were given NMN and also exercised, they lived longer than they could with either of those alone (same thing with a Resveratrol and fasting combo).

• Sinclair takes 1 gram of NMN and 1 gram of Resveratrol every morning. He mixes the Resveratrol in yogurt, because our bodies aren’t able to absorb the powder unless taken with fat or protein. Resveratrol is found naturally in the skin of grapes and blueberries, but in low amounts. There’s a higher concentration in red wine, but still not a lot.

• Sinclair regards the supplements as safe for himself and hasn’t experienced any negative side effects and says he has more energy since taking NMN (though he doesn’t tell other people to take it). He says his 80-year old father takes NMN and Resveratrol and lives an active lifestyle. Sinclair himself is 50, but looks 40. (He said his family doesn’t have good genetics for health or longevity.)

• Other things Sinclair does for himself, include: exercise, skips meals, avoids sugars and carbs (doesn’t eat desserts anymore), eats lots of green leafy vegetables, minimal protein, takes Metformin, takes vitamins D and K2, and puts his body under temperature stress (hot and cold).

• Metformin is a drug that diabetic patients take. Though Sinclair doesn’t have diabetes, he says Metformin is likely to extend lifespan and prevent cancer and heart disease even in non-diabetic patients (decreases athletic performance though). And temperature stress refers to alternating between sauna and cold bath. He says it makes yeast in the lab live 30% longer. “What you’re doing when you do that is activate longevity pathways. The trick is to activate your body’s defenses against aging.”

• Sinclair used to follow an Okinawan diet, because the island of Okinawa has a high number of people who live to more than 100-years old (10-times more than most other places). It could be that Okinawans have good genes for longevity, but it might also be because of their lifestyle. They work most of their lives and stay physically active, they fast, they eat a lot of green leafy vegetables and fish, and they stop eating when they’re 70% full.

• Damage to the “epigenome’ is a major cause of aging. The epigenome is what reads our genes. The reader loses the ability to read the genes the way it did when we were young. Exposure to radiation accelerates that process. For that reason, Sinclair tries not to have too many x-rays or get too much sun exposure. Flying in jets also exposes us to more radiation and the body scanners at airports are believed to as well.

• Sinclair is also wary of getting too much iron, especially for the elderly, because too much iron can damage our cells.

Note: Another leading researcher in this field, Aubrey de Grey, has said that the types of things mentioned above have the potential to extend human lifespan, but not by much — no more than 3 to 5 years. He says that the larger the organism, the less life can be extended through those methods. Since humans are much larger than mice, we won’t get the same degree of benefit. He also says that fasting has been shown to decrease illness in humans.

Sinclair says Dr. Valter Longo is the main expert on fasting. Here’s what I learned from Longo:

• Don’t fast any more than 12 hours at a time, otherwise you’ll be at higher risk for getting gallstones, gut leakage, and lose muscle.

• If you’re going to fast longer than 12 hours, do a “fasting mimicking diet.” Which means restricting calories to 800 to 1100 per day for a 4 to 5 day period (1100 on day 1, and 800 on days 2-5). This regime has been shown to radically improve health.

• As a general rule, the less healthy you are the more often you’d need to do it. For relatively healthy people, 2-4 times per year is enough.

• Calories for the fasting mimicking diet consist of vegetables, nuts, olive oil, vegetable soups, some vitamins, fish oil supplement, and lots of water. Basically, it cuts out all animal proteins, saturated and trans fats, sugar, carbs (except for vegetables), coffee, and alcohol. And no exercise.

• Fasting and calorie restriction cause the body to get rid of damaged cells and burn unneeded body fat, especially “visceral fat” (fat that wraps around your abdominal organs deep inside your body), which is the worst kind (because of higher risk for diabetes).

• A normal daily diet should be consumed in a 12-hour period (fast the other 12 hours), consisting of 3 meals, plus 1 snack (of no more than 100 calories), and eating should stop 3 to 4 hours before bedtime. An overweight person should probably eat 2 meals per day. For unknown reasons, skipping breakfast is associated with a greater risk for developing heart disease.

• Number of calories per day depends on bodyweight, age, and gender. For example, a 190lbs, middle-aged man (me) needs around 2500 calories per day. For women, typically around 1800-2000.

• Calories should consist of 60% complex carbs (mostly vegetables, but some whole-wheat pasta and bread is okay), 30% fat (mostly from fish, olive oil, and nuts), and 10% protein (mostly from fish, nuts, and legumes).

• High saturated and trans fat diets put you at higher risk of disease and early death. Same is true for high-fat “ketogenic” diets, though they can produce good results in the short-term (not good for long-run). Same thing for vegan and vegetarian diets (you need more protein when you’re old, because of frailty).

• High protein diets shorten lifespan and increase risk of disease. Protein consumption should be 1/3 (in grams) of your bodyweight (in pounds). For example, if you weigh 190 lbs, consume no more than 63 grams of protein per day. Elderly people need more protein, because the risk of frailty outweighs risk from protein consumption. Sinclair touched on this as well, saying that a high protein diet can help with physical performance, but you likely won’t live as long or be as healthy in the long-run. He also said that there’s a molecule called TMAO found in animal sources (especially red meat) which is linked to heart disease.

The long and the short of it is that the types of practices mentioned above can help us stay healthier while we’re alive, if not help us live a bit longer too.

P.S. I recently consumed 300mg of Nicotinamide Riboside (NR) per day for 30 days (no noticeable effects). I stopped for a couple of reasons:

• It’s expensive. $50 per month just for that small amount, which might be too little to do any good (very small dose compared to what the mice were given). Spending more for a larger dose isn’t worth it unless I know beforehand that it’s going to be beneficial (human studies are still ongoing).
• It has to be kept cool at all times, otherwise it might actually be bad for you. I have no way of knowing if it’s being stored properly before I buy it, especially since I can only get it through the mail and the warm months are approaching.