Life-and-death matters

Many readers may be disturbed or put off by this book's title. Death is a subject with depressing connotations, and most people have an instinctive aversion to contemplating it. However, the subtitle explains the focus in more detail. The book takes the reader on a journey through the science of gerontology, explaining the cutting-edge science, outlining the history, and dwelling on the speculative stuff, as well as touching upon the science fiction and fantasy aspects of some current research.

Although author Venki Ramakrishnan's first PhD was in physics, he is, of course, a molecular biologist by trade, winning the 2009 Nobel Prize in Chemistry along with two others for their work on ribosomes. He doesn't work in the gerontology industry; so, he's well-placed to understand and explain the science, without the inherent biases that arise along with financial interest. He also has the ability to write smooth, clear explanations of difficult scientific subjects.

While the first few chapters are all about the science, in the last two chapters the book surveys the social and civilisational implications of a much more long-lived society if one does come about. It gently pokes fun at the charlatans who have moved into this space, and at many of the California tech billionaires who have funded some of the research.

The author profiles quite a few eminent scientists who have been seduced by the money and name-recognition into "researching" stuff that's very likely to be dead ends (pun intended). Nor does he shrink from discussing the ethics of trying to extend human lifespan, or the challenges involved.

For example, there are many biotech start-ups with various technologies said to be under development. He estimates that the ageing industry has a listed market capitalisation of over $30 billion. Many of these start-ups have no products at all. Others offer stuff that's not known to be particularly efficacious at extending life.

According to the author, there's a fundamental mismatch in mindset when "techies" get into funding research on ageing. "Move fast & break things" may work in software development, but it can be dangerous in bioscience. Given the inherent impatience of Silicon Valley entrepreneurs and the underlying desperation of very rich men searching for eternal youth, the temptation to go down rabbit holes is understandable.

The story starts with a look at cell biology and the relationships between size and lifespan. This involves understanding genes and cellular processes believed to be involved in the processes of ageing. The book cites many scientific studies incorporating the latest research (upto 2022).

Despite the gravity of the subject, Ramakrishnan maintains a light, self-deprecatory touch throughout. He says that at least part of his interest in this subject springs from his being 71 years old, having a terrible memory (all his life), nursing worries about dementia, and suffering from chronic age-related issues like high blood pressure and moderate osteoarthritis, while still living an active, productive life.

Many of the chapters start with humorous anecdotes. For example, he describes how his attempt to do a coast-to-coast walk in the U.K. (about 300 km) was derailed by his knee flaring up. When he describes the process of scientific discovery, he often interleaves profiles of the scientists concerned (many of whom he knows personally).

The specific study of ageing is a relatively recent field. Scientists have, of course, been studying biological mechanisms and processes for much longer. At various times, they have discovered things that seem related to the ageing process, often while looking for something very different.

Some scientists, including the charismatic David Sinclair of Harvard Medical School, believe ageing can be treated as a curable disease. Then there are the charlatans or fantasists like Robert Ettinger, who popularised the cryogenic preservation of corpses and brains in the hope these could somehow be resuscitated in the distant future. There are others like Aubrey de Grey, who seems to walk close to cult territory with his assertion that the first human to live 1,000 years is probably already alive.

Over the millennia, different cultures have tried different things to try and extend lifespan, or bring people back from the dead. Scientists have looked at cell biology in detail, at protein replication, and at many of the ways these processes start to malfunction, especially as we age. They have also looked for single genes and for gene complexes that seem to have a relationship with ageing.

Studies involving twins, and the differences in the ways that twins age, have also helped to isolate some factors that probably affect the ageing process. Stress is another consideration that seems to sometimes lead to epigenetic changes that trigger ageing.

Cancer is a related area of study and not just because it is a killer. Normal cells cannot divide indefinitely, whereas cancer cells can. It would be ideal if we could switch on the mechanism that enables cells to continue dividing without triggering cancer. Large animals like elephants, whales and sharks need to replace cells more frequently, which implies that they should be more prone to cancers, but they are not. Hence, this is a big focus area.

Multiple approaches have been adopted to try and halt, or retard, the ageing process at the cellular level. For example, as cells replicate, the ends (telomeres) gradually get truncated. There have been attempts to bring about telomere extension, thus rejuvenating DNA in the elderly. Some scientists have used the methods the Japanese scientist Shinya Yamanaka found to switch on stem cell activity.

Some immunosuppressive drugs seem to have a beneficial impact on ageing, as do some anti-diabetic drugs. Wellness quacks often advocate de-oxidising the body, and de-methylating cells. However, while the methods, patent medicines and strange diets commonly offered by quacks may be useless, both approaches could have some basis in science. In a nod to Dracula, there have also been experiments with blood transfusions from young people to older ones.

Some have gone the cryogenic route, freezing the entire body in a modern-day version of mummification in the hope they can eventually be revived. Others have tried the more minimalistic approach of freezing the brain in the hope that memory and intellect can be "downloaded" and "transplanted", perhaps into a cloned body.

The science of ageing has made significant progress in a few key areas, even though we may not have a complete understanding of what exactly goes on. DNA has repair mechanisms and cells have different "alarm systems" for putting a cell to sleep (senescence) or killing it. If dead cells are not efficiently disposed of (literally eaten by other cells), it results in ageing. If protein folding malfunctions, other problems come about; and protein folding is more prone to malfunction in ageing.

The author believes that the "natural" lifespan of a human with good genes, a good lifestyle, and effective healthcare, is around 120 years. With luck and a decent lifestyle, someone can be in good health and active until late into their lives. However, he also points out that morbidities tend to develop later in life, and diseases like dementia become more likely. Dealing with dementia on a vast scale may be a big challenge in a long-lived society.

In the past 150-200 years, life expectancies around the world have doubled, more or less, due to lower infant mortality, antibiotics, insulin, better healthcare, and nutrition. But there could be a "hard limit" for the human body at around the 120-year mark. Moreover, if people do start to live and be mentally acute beyond, say, the century mark, societies will have to readjust current norms regarding retirement, pensions and so on.

This well-written, thought-provoking book provides a detailed overview of the scientific perspective on ageing. No, it doesn't promise immortality – or even an extended lifespan. But it will leave readers far better informed about what's happening in this space and what is within the realms of the possible. And, thus, it may dissuade them from blowing their savings on some snake-oil enterprise.

Devangshu Datta is a consulting editor and columnist with a focus on STEM and finance.

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