Getting old is part of life.Photo credit: Elmar Gubisch/Shutterstock
Why we die: The new science of aging and the search for immortality Venki Ramakrishnan Hodder (2024)
We are born, we grow up, we become adults, and perhaps reproduce. We may then develop increasing ailments or chronic diseases before we decline and finally – inevitably – die. These are the facts of life, at least so far, however much many of us may wish it were different.
Perhaps it could be different. Advances in aging research offer the prospect that aging and death could be postponed, perhaps even by hundreds of years, some say. Is this wishful thinking? This timely, insightful book Why we die The 2009 Nobel Prize winner in Chemistry, Venki Ramakrishnan, explains the scientific basis – and, importantly, separates fact from fiction.
Over the last century, human life expectancy has more than doubled thanks to better hygiene, improved living conditions, and health care innovations such as antibiotics and vaccines. However, the maximum lifespan has peaked at around 120 years. And towards the end of their generally long lives, many people today face the problems of ageing for longer periods.
Stop the clock
The question of how to stop aging and death has been the subject of speculation, belief and myth for thousands of years. The great pyramids of ancient Egypt were built by people who believed the pharaohs would find new life; the search for the “fountain of youth” is a perennial theme in human stories. Modern science has revealed what this search is confronting. Aging is what happens automatically in organisms that have survived the phase of life in which they normally pass their genes on to the next generation. After that, there is no selection pressure to prevent processes of deterioration and decay.
How to kill the “zombie cells” that make you age
Research has identified many biological hallmarks of aging: DNA accumulates damage, the ends of chromosomes become shorter, proteins clump together, organelles, including mitochondria, stop functioning properly, stem cell numbers decline, and organs become chronically inflamed. These problems primarily reflect increasing chemical damage to molecules that affect all cellular systems, including the maintenance, repair, and renewal processes that would normally counteract such deterioration. This sets in motion a vicious cycle that eventually triggers cellular aging or senescence and death, leading inevitably to the demise of an organism.
Ramakrishnan explains these basic processes of aging in a commendably understandable and accessible way (even if some complex concepts will inevitably require re-reading for the completely uninitiated). A fundamental question for researchers now is what is the relationship between everything that goes wrong. Is aging caused by one or more factors, and which of these predominate? Although not all scientists agree, strong evidence supports the idea that the ultimate cause is the accumulation of damage to DNA from influences such as oxygen radicals, ultraviolet and X-ray radiation, cigarette smoke, chemotherapy drugs, alcohol, many natural metabolites, and even water. This insight is crucial for deriving reliable biological markers of aging in tissues or blood. Such a feat has been achieved by the ingenious identification of epigenetic clocks in our genome. But these insights are even more important for uncovering targets that allow intervention in the aging process.
Secrets of a long life
Reports of advances in anti-aging measures, such as the discovery of “senolytics” – compounds that eliminate senescent cells – have attracted widespread public attention and significant commercial interest. But even scientists cannot always tell whether the results of a study are reliable or inaccurate, promising or only preliminary.
Although Ramakrishnan is not a specialist in aging research, he provides many insights into Why we die. He does this through extensive research: critical reading of the literature, consulting reliable specialists and, most importantly, rational, independent thinking and common sense. His interviews with researchers in the field allow him to look behind the scenes and gain interesting information that cannot be found in textbooks or scientific journals. Why we die is peppered with fascinating anecdotes, quirky characters, and valuable historical perspectives, giving it an additional dimension that goes beyond a summary of the current state of the art.
Hacking the immune system could slow down aging – here’s how
So what’s really hot and what’s not? It has long been known that restricting diets generally delays aging and significantly extends lifespan, but it’s not a popular practice, Ramakrishnan notes. He goes on to discuss the partially successful search for drugs that mimic this effect. Inhibiting a key metabolic enzyme called mTOR extends lifespan moderately in many organisms, but appears to have only a limited effect in humans. Although the author doesn’t mention it, GLP-1 receptor agonists, marketed to treat diabetes and obesity by reducing appetite and body weight, may offer a promising alternative.
The use of senolytics has raised expectations because they offer a number of benefits in mice. However, cellular aging takes many forms and is also critical for development, stress response and cancer prevention, making application in humans difficult. Such concerns also apply to the strategy of delivering factors from the blood of young donors to old recipients, which research has shown partially rejuvenates old mice. However, results from studies of reprogramming adult mouse cells into stem cell-like cells by temporarily expressing certain transcription factors that control sets of early development genes are encouraging. Such techniques could be used in humans in the distant future when safety issues are resolved.
A healthy life
But rejuvenation strategies that replace cells are not suitable for all tissue types. In particular, such methods would not work for the brain, since most neurons must remain alive and functioning throughout our lives. This represents a major obstacle, despite the development of cell culture protocols for clusters of differentiated neurons, so-called mini-brains. The name is overly optimistic, because these mini-brains are nowhere near the enormous complexity of their real-world counterparts. Even more improbable is the idea, put forward by some, that one can preserve a human brain, or even an entire body, by storing it in liquid nitrogen until technological advances allow it to be revived. Faith in such methods is perhaps comparable to the Egyptians’ belief that their pharaohs would be resurrected.
Why we die is of great interest to everyone and certainly contains lessons for scientists. Ramakrishnan, for example, distinguishes between DNA damage and DNA mutations. The processes that cause these changes are different and have different consequences – aging and cancer, respectively – and are still too often confused by specialists in aging research. Another example is the field’s focus on changes that promote longevity. Studies on animals with mutated genes that cause premature health problems or accelerate aging could be just as informative, if not more so.
This book could save investors in anti-aging companies and billionaires a lot of money. Instead of wasting their capital chasing nonexistent elixirs of eternal life, they could help humanity by supporting treatments that really show promise. Further extension of healthy lifespan can only be achieved by intervening in the basic mechanism of aging, which has been deciphered by solid scientific evidence.
