Key Points:
- Taking suggestions from other scientists, Dr. Brenner refutes premises contained within the book Lifepan, authored by Dr. Sinclair.
- Both scientists are associated with companies that sell NAD+ precursors as supplements.
- Overall, Brenner argues that Sinclair has overhyped many of the recent scientific findings in the field of aging biology.
In a letter to the editor published in Archives of Gerontology and Geriatrics, Charles Brenner, a chairman at the City of Hope National Medical Center who helped popularize nicotinamide riboside as a NAD+ precursor, reviews David Sinclair’s book Lifespan.
“Lifespan … represents a pivot in which a person central to the failure of the largest longevity medicine program in pharmaceutical history turns to the general public to retell his story,” says Brenner in the letter.
Sinclair is a professor at Harvard Medical School and the co-director of its Paul F. Glenn Center for Biology of Aging Research, where he studies sirtuin enzymes that respond to changing NAD+ levels. He and journalist Matthew LaPlante authored the book Lifespan: Why We Age, and Why We Don’t Have To, which ranked #11 on The New York Times bestseller list when it was released in 2019.
In Lifespan, Sinclair describes aging as a disease that can be reversed by various lifespan-extending interventions. In the book, he details his Information Theory of Aging, which is now supported by recently published data. The book also describes how to potentially reverse the aging process, including diet, exercise, and supplementation with various compounds, such as the plant-based molecule found in wine called resveratrol. The book was accompanied by a podcast by the same name, where dietary longevity interventions are described in one of the episodes.
Brenner’s Review of the World’s Best-Selling Book on Aging
Our Lifespan has a Limit
Dr. Brenner starts by explaining his own outlook on aging. Citing three publications (one his own), he states that our natural lifespans are limited by our genes, and we can only live for about 120 years maximum. He goes on to say that we only live long enough to reproduce and make sure our offspring reproduce. In the end, he says, we don’t have the genes to allow us to live far beyond our reproductive and caretaking years.
Is Aging a Disease, and is it Treatable?
Pointing out two questions on the back cover of Lifespan, Brenner answers them. The first is “is aging a disease?” Brenner’s answer is that aging is a risk factor for many diseases, but aging is not a disease itself. He follows by saying that the most powerful genetic mutations to extend lifespan in animal models have been in genes that control growth, establishing that growth and development are intricately linked with aging, suggesting that aging is inevitable.
“Is aging treatable?” Yes, says Brenner, in the sense that genes can be modified to change the rate of aging. He says, however, that it is easier to accelerate aging — by doing things like smoking or becoming overweight — than it is to slow aging. He then comments on well-known studies showing that caloric restriction (consuming fewer calories) extends the lifespan of mice. These studies suggest that fasting can treat aging, but Brenner disagrees with their framing, saying,
“Caloric restriction extends animal lifespan when compared to caged animals with constant access to food. However, it is more accurate to say that unrestricted access to food is a life-shortening condition that is unlike conditions in the wild to which animals are adapted.”
Brenner then makes the point that lifestyle changes can improve health, but getting healthier is not the same as reversing aging.
Do Sirtuins Extend Lifespan?
Sirtuins are enzymes that play a key role in cell survival processes like DNA repair. Brenner says that, in Lifespan, sirtuins are claimed to extend lifespan. He then cites contrary evidence, with studies showing that sirtuins do not extend the lifespan of yeast and flies, and Brenner’s own study showing that sirtuins shorten the lifespan of yeast.
Furthermore, Brenner states that Sinclair claims resveratrol is a sirtuin activator. He then cites his own paper showing that resveratrol falsely amplifies sirtuin levels because of the way sirtuin activity is measured. He goes on to explain how the positive results for sirtuins and resveratrol have been amplified by the media, whereas the negative results have seen far less exposure.
“The global interest in sirtuins and sirtuin activators was such that companies—most notably GSK—spent many billions of dollars trying to get a positive result and could not because the so-called sirtuin activators do not activate sirtuins and because sirtuins are not longevity genes,” states Brenner.
What Breakthroughs?
After Brenner describes Lifespan as a “retelling” that leaves the negative points out, he also adds that what seem like breakthroughs in the aging space also have negatives that are not conveyed to the public. He says,
“The tech and cryptocurrency bubbles of 2020–2021 pushed a great deal of private funding into companies in the longevity space. From afar, it may seem like breakthroughs are on the horizon.”
One example he gives of a pseudo-breakthrough mentioned in Lifespan is partial reprogramming, a new technology that essentially reverses the age of cells. He says that what Lifespan leaves out is a study showing that partial reprogramming can lead to tumors. Brenner also mentions CRISPR technologies, which can potentially be used to edit our genes to increase longevity. However, he states that there are no known longevity genes that we can target with this technology.
Conflict of Interest
It should be noted that Dr. Charles Brenner is the Chief Scientific Advisor for ChromaDex, the company that produces TruNiagen, which contains the NAD+ precursor nicotinamide riboside. Similarly, Dr. David Sinclair is the co-founder and member of the scientific advisory board for Metro International Biotech, which produces an NMN NAD+ precursor called MIB-626. By promoting NMN in his book Lifespan and elsewhere, Sinclair may have harmed the commercial interest of TruNiagen. Therefore, there exist a conflict of interest between Brenner and Sinclair.
Continuing, Lifespan contains Sinclair’s own anti-aging regimen, which includes the type 2 diabetes medication metformin. Brenner says that this can be harmful to individuals without type 2 diabetes, as metformin has been shown to blunt the beneficial effects of exercise (similar study), which is especially important for the health and lifespan of older individuals.
When speaking of the Lifespan podcasts, Brenner says that Sinclair makes “innumerable non-evidence-based statements” concerning age-reversal and time-restricted feeding (a form of fasting) based only on biomarkers. Brenner then says that many young adults who follow anti-aging fad diets, drugs, and practices are being exposed to drugs that “lack an evidentiary basis for their off-label adoption.”
Brenner ends by saying that “the reach of Lifespan is a problem for the world precisely because a Harvard scientist is telling fictitious stories about aging that go nowhere other than continuing hype as legendary as anything in Herodotus,” referring to lore concerning the fountain of youth by the ancient Greek historian.
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