“Lifespan: Why We Age—and Why We Don’t Have To” is a book written by David A. Sinclair, PhD, and Matthew D. LaPlante. It was published in 2019. David Sinclair is a professor of genetics at Harvard Medical School and is known for his research into the biology of aging.

In the book, Sinclair presents his research and theories about aging. He suggests that aging should be treated as a disease, and that modern medicine should be focused on preventing it. He introduces the concept of “informational theory of aging,” positing that aging is due to loss of biological information, but that with scientific advancements, we may be able to slow down or even reverse this process.

Sinclair discusses concepts such as epigenetics, sirtuins, and the role of resveratrol and other molecules in longevity. The book is a combination of scientific research, personal anecdotes, and forward-looking speculation about the potential for advances in genetic engineering, AI, and other technologies to extend human lifespan.

Why We Age

In “Lifespan: Why We Age—and Why We Don’t Have To,” David Sinclair presents the Information Theory of Aging. The theory uses the analogy of a digital information system or a computer’s hardware (DNA) and software (epigenome) to explain aging. Here’s a breakdown of the theory’s key points:

1. DNA as hardware: Our genetic code, stored in our DNA, is like the hardware of a computer. It’s relatively durable and resistant to damage, and even when damage does occur, there are numerous repair mechanisms in place to fix the errors.
2. Epigenome as software: The epigenome, which determines how the information in the DNA is read and used, is akin to a computer’s software. Epigenetic marks control the expression of genes—turning them “on” or “off”—and therefore dictate cellular function.
3. Information loss over time: Just as a computer’s software can degrade or become corrupted over time, leading to glitches and errors, the same can happen with our epigenome. These “epigenetic errors” accumulate over time due to various factors, including exposure to environmental stressors and the normal processes of cellular replication and metabolism. This leads to a loss of cellular identity and function, which Sinclair argues is a primary cause of aging.
4. DNA damage versus epigenetic noise: While traditional theories of aging focus on the accumulation of DNA damage, Sinclair suggests that it’s actually the accumulation of “epigenetic noise” (errors in gene expression) that plays a larger role in driving the aging process. DNA damage is part of it, but primarily because it can cause epigenetic changes.
5. Role of sirtuins and other longevity genes: Sinclair proposes that certain genes, like the sirtuins, play a crucial role in maintaining the stability of our epigenome. These genes are involved in DNA repair and other stress response mechanisms, and they help to resist the accumulation of epigenetic noise. However, as we age and as stressors increase, these maintenance systems can become overwhelmed, leading to increased epigenetic errors and the progression of aging.
6. Reprogramming to restore youth: Sinclair suggests that if we could find a way to “reprogram” our cells—to reset the epigenome to its youthful state—we might be able to slow, halt, or even reverse aging. His research has shown this to be possible in mice.

The book also contains a number of suggestions for lifestyle changes and interventions that, according to SInclair’s research, could potentially promote longevity and healthspan. Here are some key points:

1. Dietary adjustments:
   • Intermittent fasting and reduced calorie intake: These practices are thought to activate certain cellular pathways, including those involving sirtuins, that promote cellular repair and resilience. Autophagy, a process where the body recycles damaged cellular components, is also upregulated during periods of fasting or caloric restriction.
   • High-fiber diet: A fiber-rich diet supports a healthy gut microbiome. The gut microbiome is increasingly recognized for its role in overall health, including inflammation, immunity, and metabolic processes that could impact aging.
2. Exercise: Regular physical activity is known to have numerous health benefits, including improved cardiovascular health, better metabolic function, and enhanced cognitive health. At the cellular level, exercise stimulates various stress response pathways that can lead to increased resilience and repair mechanisms.
3. Cold exposure: Exposure to cold is thought to stimulate certain metabolic pathways, such as those involving brown fat, a type of fat that burns energy to produce heat. This may lead to better metabolic health and resilience.
4. Molecules for longevity:
   • Resveratrol: This molecule is believed to activate sirtuins, a family of proteins that play a role in cellular health and longevity. Sirtuins are involved in DNA repair, inflammation reduction, and metabolic regulation, among other processes.
   • NAD+ boosters: NAD+ is a molecule crucial for energy metabolism and the function of sirtuins. Levels of NAD+ decline with age, and boosting its levels with precursors like NMN or NR is suggested to help counteract this decline and potentially promote better cellular function and longevity.
5. Stressors: The concept of hormesis suggests that exposure to mild stressors can activate the body’s defense mechanisms, leading to increased resilience. This can include improved cellular repair mechanisms and better adaptation to future stress.
6. Regular check-ups: Early detection and management of health issues can lead to better outcomes and potentially prevent disease progression that could impact lifespan and health span.