Immortals

Andrew Steele: "Immortals: How hydra and jellyfish live forever and how people can learn their secret." Review

"Biomolecule"

All the books devoted to the problem of aging are, plus or minus, similar: their leitmotif is that it is not cancer and cardiovascular diseases that kill, but aging as a biological process. The enormous efforts and funds that modern medicine spends on the treatment of specific age—related diseases are only palliative measures that do not eliminate the essence of the problem. But if it turns out to reverse the biological arrows, the golden age will come "... and there will be no more death; there will be no more crying, no more crying, no more sickness, for the former has passed away" (Rev 21:4).

Andrew Steele's book is written in the same vein. However, it has a number of advantages. The first thing that catches your eye is an attempt to apply an evolutionary approach to explaining the phenomenon of aging as such. An entire chapter is devoted to the consideration of the most popular theories of aging today, such as the accumulation of mutations and the theory of disposable soma. The author turns to these theories from time to time in the course of the narrative, so this evolutionary approach is used not just for beauty, but works to reveal the main ideas.

The second thing that makes Steele's book more advantageous is an attempt at a comprehensive approach to explaining the aging process and, accordingly, approaches to slowing it down. Often the authors focus on one or two factors and build the whole discussion around them. For example, in David Sinclair's recently published book "The Life Plan", the emphasis was placed on the mTOR pathway, sirtuin proteins and oxidative stress (a little). And the whole therapy of aging (if I may say so) is based, according to the author, on drugs and methods that affect these pathways and proteins. By an "amazing" coincidence, most of the drugs described in the book were developed by Sinclair himself. Steele, as I mentioned, chose a different strategy. Based on the article "Signs of Aging" [1], published in the prestigious journal Cell in 2013, he identified 10 reference points, or criteria by which one can judge what happens in the body during aging.

There is no critical approach in Sinclair's book at all, which turns it into a weighty marketing booklet filled with poorly covered self-promotion. — Approx. the author of the review

So, we get old if we have:

• mutations accumulate;
• telomeres are shortened;
• proteostasis is disrupted;
• epigenetic changes occur;
• aging cells accumulate;
• problems with cellular energy begin;
• intra- and intercellular signaling fails;
• the intestinal microbiota changes;
• the stem cell pool is being depleted;
• the immune system is disrupted.

And it's hard to argue with this argument (and I don't want to). Based on the selected criteria, Steele analyzes approaches aimed at slowing down aging. Here, however, the problems of biogerontology arise in full growth before the reader, because the impact on each individual aspect of aging is a non—trivial task. For example, how to replenish the pool of hematopoietic stem cells without resorting to bone marrow transplantation? Is such a risky approach necessary at all to "throw" yourself another three to five years of life in relative health? And what about calorie restriction? The method, which has proven itself well in nematodes and mice, has not been practically tested on primates, and the results available to researchers are so scattered and ambiguous that it is difficult to say whether the method will have any effect at all if clinicians undertake its widespread implementation. The author, it seems to me, understands the limitations of existing approaches perfectly.

"To truly cure aging, we need to use a more holistic approach of systems biology. We need to understand that cells and bodies do not consist of a set of isolated phenomena, each of which can be corrected separately, but of a complex system of components interacting in intricate networks with each other and even with themselves," Steele writes.

In other words, there is always a risk of "rejuvenating" one system, crippling another, or failing to achieve any result due to underestimating the contribution of other systems and processes. Fortunately, in the chapter devoted to the reprogramming of aging, the author does not fall into crazy futurological arguments that literally tomorrow genetic engineering will help us defeat old age.

"If this sounds futuristic, it's because it is," Steele writes, "we're just beginning to understand how networks of genes interact inside cells and how signals are transmitted throughout the body. In some ways, we are lagging behind the construction of detailed predictive models of human biology."

However, otherwise, the author's rather balanced approach to assessing the prospects of senolytic drugs begins to suffer from excessive optimism. Here we are already smoothly moving on to the shortcomings of the book . The gap between experimental developments on genetic reprogramming of aging and clinical implementation is obvious to both the author and the reader. At the same time, there is an equally impressive gap between clinical trials and preclinical testing of drugs on animals. Unfortunately (and readers of Steele's book should know this), most clinical trials fail. Some promising drugs do not even reach randomized trials, since their uselessness becomes obvious already in the first or second phases. In pharmacology, there is even such a term as "the curse of winners", when a compound that has shown miracles in animal experiments fails in human clinical trials. For example, in the laboratory of behavioral neurogenomics The ICIG SB RAS, where I work, has a vial with a substance called xaliproden, which in the early noughties was predicted to win over Alzheimer's disease — it coped so well with amyloid deposits, restored neurons and returned lost cognitive abilities to mice. But, alas, already in 2007, this substance was written off, since no positive effects of the drug were found in the second phase of the tests. And no, later the subjects did not miraculously get better. The drug simply does not work on humans. And the case of xaliproden is just one of thousands of similar ones. Actually, the tasks of scientific education are to show things as they are, the tasks of propaganda are to give wishful thinking. In my opinion, the substitution of scientific education on aging with the promotion of anti-aging therapy distorts the idea of ordinary people about the possibilities of science and medicine and contributes to the formation of magical thinking.

One small but noticeable drawback of the Russian edition is associated with the free translation of the title. If the original name sounds like Ageless: The new science of getting older without getting old, then in the Russian version appeared "Why hydra and jellyfish live forever and how people can learn their secret." This greatly shifts the emphasis. To be honest, I thought that the book would describe the study of biology of negligibly aging animals, and as if I was deceived in the end. Of course, it's not the author's fault. Apparently, realizing that the degree of optimism in the book is insufficient, Andrew Steele added an entire chapter to the book with a set of tips on how to make his life (and old age) healthier and at least slightly delay the inevitable end. A set of scientifically based tips is perhaps traditional for books on aging:

• don't smoke;
• don't overeat;
• exercise;
• watch your sleep mode;
• get vaccinated;
• take care of your teeth;
• don't forget about the sunscreen;
• monitor your pulse and blood pressure;
• do not take vitamins and supplements unnecessarily;
• if you are lucky to be born a woman — rejoice, you will live longer;
• do not try to take senolytics yourself! (the latter, apparently, is addressed to homegrown biohackers).

I'm not against the suggested tips, they all seem quite reasonable. Here, however, there are a number of nuances. To follow all these tips, you are strongly recommended to be a representative of the middle class in a developed democratic country.

Daniel Lieberman in the book "The History of the Human Body" cites such curious data: from 1985 to 2000, the purchasing power of the US dollar decreased by 59%, which led to a twofold increase in prices for fruits and vegetables, while the prices of sweets fell by 25%, and soda became cheaper by 66%. And if a burger with potatoes in 1955 would have brought you 412 calories, then for the same money (adjusted for inflation) in 2013 you would have received a portion of 920 calories. The conclusion, it seems to me, is unambiguous: healthy nutrition — (drum roll!) this is an expensive pleasure available to people with normal incomes. Interestingly, Lieberman also points out that in the United States, newborns with a weight deficit are more often born to black women than to white women, and this indicator (11% vs. 5.5%, respectively) has not changed since 1900. In other words, one of the main problems facing the prolongation of life and preservation of health in old age is overcoming property and social inequality. Authors of books on the biology of aging usually forget about this "insignificant" moment. Steele even has this phrase: "Aging is a curse that has struck the developed world." Pay attention to the word "developed". It's as if people in developing countries don't age or don't want to live long. In general, as you want, and understand, there is no explanation in the text.

Speaking of Russia, we can also recall what I would call the "Soviet diet" — boiled-overcooked soup, mashed potatoes with a cutlet, pasta in navy style, everything is fatty and with bread mixed in. Despite the fact that now, unlike the eighties, tomatoes in the middle of winter do not seem to be an unprecedented exotic, many Russians (especially older ones) continue to eat junk food. The reason is probably that, according to official data, 20.9 million residents of Russia (almost 17% of the population) now live below the poverty line.

Often the authors (and Steele is no exception here) show how much our civilization has changed over the past centuries. Until recently, they say, they lived a miserable short life in dirt and disease, and now they have built an abundant "eden". In this "garden of Eden", however, there are snakes that are usually not noticed. I mean depressive disorders. I will not go into the subtleties of statistics, I will only say that in 2019 there were 700,000 deaths due to suicide [2]. This is many times more than the mortality from all neurodegenerative diseases combined! Life in a highly urbanized world is full of stress fueling depression, but how to live with it and how to age is unclear. No one offers recipes on this score.

As a result, we have a fairly strong popular science book on biogerontology, freed from many kinks and shortcomings of its predecessors, but at the same time not devoid of characteristic features of literature on aging. One may or may not share Andrew Steele's view of the prospects for achieving negligible aging, but one cannot but agree that reducing the human suffering that old age is full of is a great humanistic goal worth striving for.

Literature

Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer. (2013). The Hallmarks of Aging. Cell. 153, 1194-1217;
Duleeka Knipe, Prianka Padmanathan, Giles Newton-Howes, Lai Fong Chan, Nav Kapur. (2022). Suicide and self-harm. The Lancet. 399, 1903-1916.

About the author
Andrew Steele is a British academic, activist and writer. After receiving a degree in physics from Oxford University, he moved into the field of computational biology and worked for some time at the Francis Crick Institute, where he developed machine learning methods for decoding sequencing data. Steele has written for the Guardian, Telegraph and Wall Street Journal. In addition, he has his own YouTube channel. Steele is also the chairman of the foundation Science is Vital and the founder of Scienceogram, a project that aims to draw attention to the small amount of funding for science compared to the importance of the problems it solves.

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