Calorie restriction traced back to protein/methionine restriction. Better to just fast and take melatonin (sustained-release). 16:8, 18:6, 20:4, 24:24, 36:12, 36:36, etc. I am biased toward 36:36.

1-2 extended fasts per year.

I am wondering about another approach involving a bumping up of protein (0.75 g/lb for 2 days, 1.00 g/lb for 2 days, and 1.25 g/lb for 2 days) and a 42-hour dry fast wrapped around the 7th day. Melatonin (and calories missing on the 7th day) would be taken on the 6 feeding days. Last meal 3-4 hours before bed either way. The fast resensitizes to protein, same as happens when it's bumped up on 3rd days.

While many cry out against mTOR, it is responsible for synthesis of many relevant proteins: creatine, glycine, collagen, etc. The issue is more with mTOR being out of balance with AMPK. Melatonin and dry fasting helps restore the balance.

Ideally, one would increase IGF-1 as much as could be done naturally (ie, vitamins/minerals and eating frequency rather than excess protein or direct supplementation). DHEA, melatonin/progesterone, and hGH would then be adjusted to match the associated growth/pubertal year (eg, matching hormone levels of a 15 year old).

There's a few specific, actionable suggestions at the very end of the book - particularly a couple of pills he takes.

But regardless, my interest is as much in the general progress that's being made and the speed at which it's accelerating. It left me feeling extremely optimistic about what the next 20-30 years is going to hold in terms of developments in anti-aging science. Unless we blow ourselves up in the near future.

Caloric restriction (beyond staying at a healthy weight) has never been shown to actually extend the lifespan of humans, or any primate.

While evidence is emerging, there are ongoing primate and human studies that suggest there is benefit to caloric restriction. This recent review is a good overview of current evidence, studies, and mechanisms:

Balasubramanian, Priya, Porsha R. Howell, and Rozalyn M. Anderson. “Aging and Caloric Restriction Research: A Biological Perspective With Translational Potential.” EBioMedicine 21 (June 19, 2017): 37–44. https://doi.org/10.1016/j.ebiom.2017.06.015.

For primates, this is a good review:

Mattison, Julie A., Ricki J. Colman, T. Mark Beasley, David B. Allison, Joseph W. Kemnitz, George S. Roth, Donald K. Ingram, Richard Weindruch, Rafael de Cabo, and Rozalyn M. Anderson. “Caloric Restriction Improves Health and Survival of Rhesus Monkeys.” Nature Communications 8, no. 1 (January 17, 2017): 14063. https://doi.org/10.1038/ncomms14063.

Abstract: Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.

For human studies, here's a recent one:

Redman, Leanne M., Steven R. Smith, Jeffrey H. Burton, Corby K. Martin, Dora Il’yasova, and Eric Ravussin. “Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging.” Cell Metabolism 27, no. 4 (April 3, 2018): 805-815.e4. https://doi.org/10.1016/j.cmet.2018.02.019.

"Findings from this 2-year CR trial in healthy, non-obese humans provide new evidence of persistent metabolic slowing accompanied by reduced oxidative stress, which supports the rate of living and oxidative damage theories of mammalian aging."

A randomized controlled trial would be great, but that experiment literally isn't going to happen in our lifetimes.

So we have to make the best of other evidence, like animal studies (rats have increased lifespan on restricted calories), observational studies, and biomarkers.

Metformin is mentioned 30% of the way through.

Are you taking it?

The actionable stuff will be 3 dot points as with all books.