Lifespan: Why We Age – and Why We Don’t Have To is a remarkable book by Harvard professor David Sinclair. Sinclair postulates that aging is a disease and can be “cured” by activating the right pathways.
David Sinclair is a Sydney-born biologist who earned his Bachelor of Science and PhD at the University of New South Wales (NSW). He is now a professor in the Department of Genetics and the co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. He also has a lab in his alma mater UNSW.
His work focuses on aging and how to slow it down or even stop it. This includes the study of molecules such as resveratrol and nicotinamide adenine dinucleotide (NAD), and proteins such as sirtuins, all of which have roles in longevity pathways.
Sinclair does not fall into the “technology is not natural” trap, and thus is involved with several biotechnology companies. He is also co-founder of the journal Aging.
Lifespan: Why We Age – and Why We Don’t Have To
David Sinclair authored this book with writer Matthew D LaPlante to translate the science into a very approachable book. I think having a background in science will help understand all the content more easily, but I don’t think it’s mandatory.
I’m glad I bought the audiobook because:
- It’s narrated by the author
- It contains in-between-chapter bits where Sinclair and his co-author exchange thoughts that came up during the process of writing this book
Part I: What We Know (The Past)
The book starts off with the author’s childhood in Sydney’s Northern suburbs and how her relationship with her paternal grandmother and his mother’s death spiked his interest in aging. To me, the highlight of this first part is the explanation of how information is stored in our bodies: digital data (the genome) vs analog data (the epigenome). This analogy works because, as explained by Sinclair, analog information degrades over time. Similarly, changes in the epigenome are what cause aging.
The second analogy is that of a demented pianist, who progressively starts playing off notes (DNA breaks) during a concerto. The piano (the genome) is not the problem, but the pianist (the epigenome) is. Occasional off notes may not noticeable but when they happen more frequently, they become an issue. Same with aging.
In this part Sinclair also introduces the genes and molecules related to longevity: sirtuins, mTOR and AMPK, all of which are activated by biological stress. Sirtuins are conserved in all species and are part of a survival circuit. In mammals, they have an important role in many processes, including cell division, DNA repair and glucose metabolism.
The author also explains how hormesis works to activate those same pathways, and that it can be achieved through some types of exercise, intermittent fasting, low protein diets and certain molecules. NMN is a precursor of NAD that might have a similar effect to exercise.
Most people treat aging as a normal part of life, but the author postulates that aging is a disease. It deteriorates our fitness and physical resilience, and it’s the main risk factor for most diseases.
Part II: What We’re Learning (The Present)
In this section of the book the author explains which interventions have been proven to correlate with longer and healthier lives. These include caloric restriction, intermittent fasting (including time-restricted feeding and fasting-mimicking diets), animal protein restriction, moderate exercise, high intensity interval training (HIIT) and extreme thermic exposure (e.g. exposure to cold, use of saunas). He also talks about exposure to chemicals in the air, plastics and radiation as causes for DNA breaks.
This section also mentions the compounds that have been discovered to have an effect in aging: rapamycin, metformin, resveratrol and nicotinamide mononucleotide (NMN, a precursor of NAD). Note that there are caveats with each molecule taken as a supplement, which I will not cover in this review.
Another topic in this part of the book is the discovery of methylation of DNA as an indicator of biological age, as well as the controversies around gene editing, such as designer babies.
Another big topic in part II is the promising applications of gene sequencing, including the ability to detect diseases before symptoms arise and the potential use of wearables for telling us what we should eat to balance our nutrient status.
Although Sinclair is an optimistic guy, and gets flack for it, he ends up on a sombre note quite accurate for the times. He says he’s sure a virus similar to influenza will mutate and kill 50%+ of the population who gets it, which will happen just by touching a doorknob. I don’t think this is meant to be a fatalistic premonition, but rather a warning of what back when the book was written was yet to come.
Part III: Where We’re Going (The Future)
The phrase that summarises the author’s view on the future is “knowledge is multiplicative and technologies are synergistic”. As mentioned before, Sinclair is an optimist. He acknowledges we have surpassed the Earth’s carrying capacity but that the problem is not just overpopulation, but consumption and waste. He also postulates that an older population wouldn’t represent a burden to the economy if it stays healthy and can continue being useful to society.
A couple of quotes from this last part that summarise what the author postulates are “aging is not just a disease but it’s the mother of all diseases” and “most people are not afraid of losing their lives, they are afraid of losing their humanities”.
David Sinclair finishes off this book by sharing what he does in terms of supplementation, diet, exercise and other lifestyle habits.
In addition, I recommend checking out the following YouTube videos: