Nick Ktistakis reviews “Why We Die” by Venki Ramakrishnan

Nick Ktistakis, group leader in the Institute’s signalling research programme, reviews the recent release from scientist and author Venki Ramakrishnan.

One of my scientific highlights of last year was reading the book on ageing by Venki Ramakrishnan: 'Why We Die: The New Science of Ageing and the Quest for Immortality', and hosting him at the Institute for a Distinguished Lecture Seminar on the topic.

As Venki makes clear at the beginning of the book, he is neither an expert in the field nor does he have “skin in the game” of the science of immortality. He is simply a Nobel Prize winning biochemist looking at the ageing field from the outside with interest and – quite frequently – critical attitude. This is an important point to make in view of the fact that in the last ten years alone more than 300,000 papers have been published on ageing and billions of dollars have been invested in over 700 startups and more mature biotechnology and pharma companies that aim to tackle ageing. Added to this is the endless general fascination in the media with ageing and the possible ways to delay it. In this environment, hype, personal promotion and manipulation of information can be rife leading to great confusion and misunderstandings. Venki’s book can serve as a source of genuine and honest information including on the history of ageing research and the basic biology underpinning some of its most important findings. An added bonus is that in the process of discussing the science of ageing, Venki also provides a very extensive and clear introduction to most significant advances in biology that connect to the ageing field such as the pathways of DNA damage and repair, the regulation of ageing by epigenetic mechanisms, the connection between nutrient limitation-mTOR activity-lifespan extension, how mitochondrial function is important for cell physiology and ageing mechanisms to give just a brief list. Importantly, Venki covers these areas by discussing them - when necessary - with prominent scientists in the field who provide unique and really useful insights. There are 238 notes at the end which explain how various statements in the book came about, and exactly how the many questions that the author had were answered by the various experts. 

The book finishes with two important chapters, one on the anti-ageing efforts by important players in the field as well by those with a less sterling reputation (the chapter is titled “Crackpots or Prophets?”) and a philosophical essay asking the question whether extension of lifespan to extreme levels is actually something desirable for humanity in general. As with the rest of the book, all of this is written with a personal touch (we learn quite a bit about Venki and his family along the way) as well as a benevolent but, when necessary, sarcastic tone that exemplifies for me the way a scientist sees the world and tries to evaluate things that matter.

As somebody working in an Institute focused on ageing I found the book very useful, especially as it tries to discuss this complex topic always from a scientific point of view. When we first started thinking about our work on ageing as an Institute, one of the biggest concerns was to separate what was known based on scientific facts and what was speculation meant to titillate or peddle products. It was important to draw very clear lines so as to maintain our reputation as scientists and to identify research areas in ageing amenable to our expertise on molecular understanding of physiological functions. Fortunately, as the field of ageing has matured, the balance of good science vs hype is also getting better, and the core of this phenomenon is nicely reflected in Venki’s book.  

One area covered briefly in the book is the interesting history of ageing as a paradox in evolutionary biology and how various theories were put forward to explain it. This was first discussed by Peter Medawar in 1952 in a lecture delivered at UCL and titled “An Unsolved Problem in Biology” where he posed the question why has ageing been selectively maintained if it does not confer an evolutionary advantage. The answer that he proposed is that evolution does not “care” past the reproductive age and therefore mechanisms such as ageing that happen later are not subject to evolutionary selection either way. Many additional theories elaborated on this general idea, but coverage in Venki’s book is sparse. I suspect that the author feels less inclined to spend a lot of thinking on matters that are somewhat speculative, and this has probably served him well in his scientific career. Nevertheless, because ultimately we will have to understand ageing in evolutionary terms, it would have been useful to have a longer discussion here, perhaps Venki could make this a topic for his next book.

During his visit at the Institute, Venki was very gracious and happy to talk to several group leaders not so much on ageing but on his true love which is ribosome biology and translational control although his talk was primarily based on his book. He finished the visit with a discussion with some of our PhD students who, as he told me afterwards, impressed him with how serious they were about ageing research!