This article is a recommended preface by Professor Wang Zhao of the School of Pharmacy of Tsinghua University for Professor David Sinclair's book "Longevity When Human Beings No Longer Age".
Professor David Sinclair, director of the Institute of Aging Biology at Harvard Medical School, has made a series of epoch-making scientific achievements in the past 20 years and is one of the main catalysts for the process of human immortality, and his book "Lifespan: Why We Age and Why We Don't Have To", published in 2019, topped the New York Times and Amazon bestseller lists, is a treasure book that takes readers to the forefront of anti-aging science.
In June this year, the Chinese Simplified edition of Lifespan was officially launched (renamed "Longevity When Human Beings No Longer Age"), and the Time School was honored to provide academic support. With the permission of Professor Wang Zhao, we published the first Chinese recommended preface of the book as follows for the benefit of readers.
Why do we age? Can we not age? David Sinclair's 2019 book, Lifespan: Why we age and why we don't have to, from Harvard Medical School's Department of Genetics, raises such questions once again.
图注：《lifespan》 by David Sinclair
David and I met many years ago when we attended the Cellular Aging Forum at Cape Cod in Boston, USA. Later, I spent some time at Harvard Medical School as a visiting professor, and I happened to be in the new research building in Nagagi with David, and I didn't have much intersection during this time. From the title of his new book, we can see that the book has two core concepts, one is lifespan and the other is age. Let's start with lifespan.
01
It can be said that at the same time that life was born on the earth and had to evolve and upgrade due to the coercion of the environment, it was accompanied by death. The length of time between life and death is what we usually call life span, and it can be said that life span is a period of time that begins with birth and ends with death. Therefore, from the very beginning, death is necessary for the evolution and upgrading of life, and there will be no evolution without life and death, and life repeats and updates the evolutionary process of natural selection and survival of the fittest in the iteration of life and death. This is the nature of lifespan. Of course, with the evolution of life forms, there are also different lengths and types of lifespans. Death is the premise of evolution, and as long as it is still evolving, death is inevitable. Individuals do not live forever, because natural selection does not allow them to live forever in this world.
Illustration: The Evolution of Aging (Excerpt from Longevity)
When people talk about lifespan, most of the time they refer to the actual lifespan of individual human beings, that is, how many years a certain body actually lives. Whether it is premature death or early death, whether it is a red face or an early death, or a dying life or a crane fairy, all refer to its actual age, the English is lifespan; If it is a group, it is the average life expectancy of a certain group. In fact, there is also a concept of life expectancy that refers to the "maximum lifespan", and the current maximum life expectancy of human beings is generally considered to be about 120 years old. From recorded history, there are basically no humans over 120 years old. Actual lifespan (or average lifespan) and maximum lifespan are two very different concepts, the former being essentially random and the latter essentially evolving. We say that the life span of human beings has been greatly extended for more than 200 years, or that they have extended their lives through various methods and measures, which basically refers to the former; And the maximum lifespan of human beings has not increased much in this time period.
Further, why should life have a term? Why can't it be eternal life? Because of the need for evolution. There is life and death before there is natural selection, in order to achieve the survival of the fittest, in order to complete the evolutionary progression, and immortality means the stagnation of evolution. So no matter how long you can live, as long as you are still evolving, death is necessary. So why is the maximum lifespan of humans about 120 years? Why can't it be 180 years old? This is more complicated to say, simply related to the number of divisions of human somatic cells, as Schrödinger said in his famous "What Is Life", "One of my somatic cells is only the 50th or 60th generation of the egg cell I am." "The number of human cell divisions is 50 times, and the average cycle of each division is 2.4 years, so the natural lifespan of humans is about 120 years. It is also believed that the natural lifespan of mammals is equivalent to 5-7 times its growth period, and the reproductive period of humans averages about 18 years, so the natural life expectancy is theoretically 90-126 years old. In the Bible, the Lord in Genesis says, "My Spirit will not dwell in the human body forever, for He is flesh and blood." His life expectancy will be 120 years. The traditional Hebrew language says "May you live to the age of 120". Records of different ethnic groups and cultures in ancient and modern China and abroad show that the life expectancy limit of a person is about 120 years old.
Note: Leonard Hayflick found that there is a limit to somatic cell division
02
Let's talk about aging. Unlike death, aging is not an evolutionary event, or an event that is ignored by evolution. But you can only grasp this when you look at aging from an evolutionary perspective. Therefore, it is necessary to understand and study aging from an evolutionary perspective.
We know that from an evolutionary perspective, reproduction and inheritance are its sole purposes, so all the genes preserved by long-term evolutionary natural selection, as well as all the functions and resource allocations of the body (not just energy allocation), are underpinned by this ultimate purpose. When development matures and reproduction is completed, these supporting factors begin to be removed, which is the beginning of aging.
Some people think that the power of natural selection weakens after reproduction, but in fact it is no longer effective. The so-called "weakening" is nothing more than a shadow of the inertia of natural selection. The brakes of the basic evolutionary power make the body as a gene transmission carrier begin to undergo various degenerative changes, and observing and studying aging from different angles has produced various theories of aging formation, such as tissue and organ wear theory, gene mutation accumulation theory, antagonistic multi-effect gene theory, disposable body theory, etc., all of which have explained the formation of aging phenomena from different angles or levels, and the latter two theories have incorporated some evolutionary ideas.
Some people also explain aging from the basic laws of physics, believing that aging is a process of entropy increase. But if we have to explain aging in terms of the second law of thermodynamics, entropy increase begins at birth, not after maturation and reproduction. Therefore, entropy increase may be appropriate to clarify the entire life course of man, but it is somewhat one-sided and limited to the description of aging alone.
As mentioned earlier, when life evolved on this planet, there was death. Death arises with evolution, is a product of evolution, is necessary for evolution. Compared with the history of human evolution, from the birth of the nobominee 3 million years ago to the present, aging is only a matter of nearly 200 years, which is a very "young" concept. Before this, the life expectancy of human beings was only more than 30 years old, and more than 40 years old was a high lifespan, which was very rare.
Therefore, aging and death should be understood separately, and they should be examined from an evolutionary perspective. The end of life is not necessarily the result of aging, the ancestors of human beings basically died of predation, disease, accidents and infections caused by them, and hunger, etc., basically there is no death after aging, so aging is not a necessary prerequisite for death. Aging, which is mainly "caused" by the progress of medical and health services, the development of social and cultural education, and the improvement of dietary nutrition, reflects the process of time between individual maturity and death, and has its unique spatio-temporal characteristics.
From a chronological point of view, aging is a process of development, an experience between reproduction and the end of life (such as the initial old age, the middle age, the longevity period and other staging methods); Spatially, aging is a state of change, interwoven by a variety of changing factors (such as health, sub-health, disease, disability, etc.). The time course of aging can be compressed (increasing the length of healthy lifespan), and the spatial state of aging can also be changed (reducing the state of disease and disability), which is anti-aging.
Illustration: Characteristics of Aging (Excerpt from Longevity)
There is no biological law that says we have to go through aging. There is no doubt that aging increases mortality, but aging is not a necessary and prerequisite for death. It is precisely because aging does not occur programmatically, not as an evolutionary event, that it leaves us with a lot of room for anti-aging. Anti-aging is not "going against the grain", but going with the flow. But we must always rationally realize that not aging does not mean not dying, and no disease and no disaster does not mean eternal life. Like our laboratory animals, no matter how good the conditions you give Him, He will not live forever. So the purpose of anti-aging is to pursue health rather than immortality.
Is aging a disease? This issue has also been debated for many years. The reason for the debate is that there are academic issues and non-academic objections. If aging is not a disease, it is just that, if it is a disease, whether to treat it, how to treat it, whether it can enter medical insurance and a series of other problems will appear. It depends on how we define disease. If the disease is "a deviation from the normal form and function of the human body" (of course, the premise of this definition is that everyone has a unified understanding of the normal form and function of the human body), then aging is undoubtedly a disease. This issue has been basically settled in the eleventh revision of the International Classification of Diseases, the global diagnostic information standard published in June 2018. The revised edition adds a disease name code-named MG2A, "Old Age", which is defined as advanced age or aging excluding mental disorders and Alzheimer's disease, and is recommended that countries adopt it from January 1, 2022. Since aging is a disease, it should be treatable, which is the legal basis of various anti-aging therapies.
03
Is there an easy way to stay healthy and slow down aging? Yes! It's "shut your mouth and open your legs." David emphasizes in the book that if I had to give the only advice to slow down aging and promote health, it would be to eat less; If you add one more, it's 10 minutes a day! Do I still need it? If you don't think starvation is enough, wear less (keep your body relatively cool). But this seems to be more suitable for people who are relatively younger, and less suitable after the age of 7 or 80. To sum up, in fact, it is "survival in adversity", I have to be hungry to eat enough, I have to be cold to wear warm, I have to be tired to be comfortable, and its unified mechanism is to activate the most primitive survival circuit in the human body. These mechanisms are gradually formed and retained in the life inheritance of human beings in the long-term evolutionary process, and are the inscriptions left in the human genome by the harsh environment (insufficient food, lack of clothing, exhaustion, etc.) in the evolutionary process, which does not disappear because of the modern well-fed, leisurely and comfortable lifestyle, and still plays a vital role in survival at the most basic level of life. In fact, the basic function of these circuits is to temporarily lie down and wait for the improvement of the environment when the environment, especially the nutritional conditions, are poor so that reproduction can proceed smoothly, and prolonging life is not its initial goal, but only a by-product of the expedient measures taken by organisms in order to wait for suitable development and reproductive opportunities.
04
Finally, one issue that needs to be clarified is that anti-aging is not the same as anti-death (which is also a common problem in many current works and literature on aging biology, which mixes aging, longevity, and death). The various anti-aging methods mentioned above, whether you eat less, walk fast, or use certain drugs and health products, there is no (at least so far) scientific basis to show that it can extend your maximum lifespan. But these methods and measures can not only improve your health later in life, but also extend your physiological life as long as possible within the biological life limit, improve the quality of life and the happiness of life while reducing the burden on individuals, families and society. Our anti-aging purpose is to reduce the occurrence of disease and disability, to maintain health and vitality, not simply to prolong life. Whether the maximum life expectancy can be achieved in a shorter period of time, the current scientific research has not given a definite answer. At least from the evolutionary process, this will not be a simple and easy change. Perhaps cell reprogramming, stem cell and regenerative medicine, organ transplantation, or some other method can change the limit of human life, but the implementation of these methods is mostly done in the later stages of an individual's life, that is, it is no longer hereditary and does not contribute to the evolutionary process. What is the long-term group and social effect of such a change is not easy to estimate in the short term. But who can say for sure what will happen in the future?
Illustration: Imagining Techniques to Extend Life (Excerpt from Longevity)
"End aging. We will live a life free of disease or disability. David made bold remarks in his new book.
Wang Zhao
May 1, 2022
Double Qing Zhai in Tsinghua Garden, Beijing
—— TIMEPIE ——
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