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.
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.
This is basically meaningless if you don't qualify why you think so. He is a harvard medical doctor and one of the leading researchers in the field, so I'd like to know what makes him a fraud
Just as an FYI, the "scam artist" David Sinclair is in fact one of the leading scientists in the world studying the biomechanics of longevity:
David A. Sinclair, Ph.D., A.O. is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. He obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney in 1995. He worked as a postdoctoral researcher at M.I.T. with Dr. Leonard Guarente where he co discovered a cause of aging for yeast as well as the role of Sir2 in epigenetic changes driven by genome instability. In 1999 he was recruited to Harvard Medical School where he has been teaching aging biology and translational medicine for aging for the past 16 years. His research has been primarily focused on the sirtuins, protein-modifying enzymes that respond to changing NAD+ levels and to caloric restriction (CR) with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer. The Sinclair lab was the first one to identify a role for NAD+ biosynthesis in regulation of lifespan and first showed that sirtuins are involved in CR in mammals. They first identified small molecules that activate SIRT1 such as resveratrol and studied how they improve metabolic function using a combination of genetic, enzymological, biophysical and pharmacological approaches. They recently showed that natural and synthetic activators require SIRT1 to mediate the in vivo effects in muscle and identified a structured activation domain. They demonstrated that miscommunication between the mitochondrial and nuclear genomes is a cause of age-related physiological decline and that relocalization of chromatin factors in response to DNA breaks may be a cause of aging.
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”.
Wow, thanks for the context. Would still love more book suggestions on the topic if you happen to know any outside of his book; there's been some great papers linked in the thread so far but only one book suggestion unfortunately.
If you must read a book, Ending Aging by Aubrey de Grey is maybe the best introduction but IMO you're still better off reading the papers/tracking the latest research if you're interested in the topic. You'll save a lot of time and be more up to date, as it's a rapidly developing field:
West, Michael D, Hal Sternberg, Ivan Labat, Jeffrey Janus, Karen B Chapman, Nafees N Malik, Aubrey DNJ de Grey, and Dana Larocca. “Toward a Unified Theory of Aging and Regeneration.” Regenerative Medicine 14, no. 9 (August 28, 2019): 867–86. https://doi.org/10.2217/rme-2019-0062.
Shetty, Ashok K., Maheedhar Kodali, Raghavendra Upadhya, and Leelavathi N. Madhu. “Emerging Anti-Aging Strategies - Scientific Basis and Efficacy.” Aging and Disease 9, no. 6 (December 4, 2018): 1165–84. https://doi.org/10.14336/AD.2018.1026.
Brown-Borg, Holly M., and Rozalyn M. Anderson. “Metabolic Adventures in Aging Research.” Molecular and Cellular Endocrinology, Metabolism of Aging, 455 (November 5, 2017): 1–3. https://doi.org/10.1016/j.mce.2017.08.012.
Longo, Valter D, Adam Antebi, Andrzej Bartke, Nir Barzilai, Holly M Brown-Borg, Calogero Caruso, Tyler J Curiel, et al. “Interventions to Slow Aging in Humans: Are We Ready?” Aging Cell 14, no. 4 (August 2015): 497–510. https://doi.org/10.1111/acel.12338.
López-Otín, Carlos, Maria A. Blasco, Linda Partridge, Manuel Serrano, and Guido Kroemer. “The Hallmarks of Aging.” Cell 153, no. 6 (June 6, 2013): 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039.
A couple resources for keeping track of recent developments:
