Why aging can be avoided: excerpt from the book "Hacking the code of aging"

A huge variety of types of aging in plants and animals hints at the possibility of control over this process.

People age gradually, but some animals start to grow old very quickly at the end of life, while others do not grow old at all, and some may even get younger. The variety of mechanisms of aging in nature should alert the lovers of generalizations - especially against the generalization of the inevitability of aging.

Bacteria are reproduced, symmetrically sharing in two. What can aging mean for bacteria which, after division, have no difference between parent and child? Single-celled protists like amoebas also reproduce symmetrically, but they still invented a way to age. And even among macroscopic life forms, life expectancy is extremely different depending on the local ecology and speed of reproduction. This could hardly have happened as a result of a universal and unshakable process; such a fine adjustment clearly speaks of adaptation.


Mayfly die quickly and suddenly at the end of their reproductive cycle.
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Life expectancy varies from mafusilovoy to genetic kamikaze, dying by spring noon. Dragonflies live for four months, adult mayflies - half an hour. We live about 70 years, and the ginkgo meristem can be millions of years old. This diversity is even more impressive if we recall that the genetic basis of aging is common to many creatures, from yeast to whales. But somehow the same genetic mechanisms inherited from common ancestors at the dawn of life were modified to create very different lifespans, from hours (yeast) to thousands of years (sequoias and aspen poplar).

Not only the life expectancy differs greatly, but also the pattern of decay during this period. Aging can occur gradually throughout life (lizards, birds), or the body may not age at all for decades, and then suddenly die (cicadas, agave).

Our inner killer works quietly, like an evil empress poisoning her husband; but for other creatures, internal killers work faster, and for some, there is no genetic death program at all. Such diversity is an unequivocal signal of a feature formed by natural selection, and not the inevitable law of entropy.

Since aging biomarkers are so different in different creatures - and even in different representatives of the same species - it is very difficult to derive a universal definition. A person may turn gray prematurely, naked calf can be covered with wrinkles. For an actuary, the answer to a question is simple, even if only statisticians like the answer: aging is an increase in the death rate. In other words, in the process of growing up the risk of death of the animal increases.

For example, a 20-year-old man has 99.9 chances to live to 21 years. That is, his chances of dying are 1 in 1000 a year. If this were the case, then the 40-year-old would also have 1 chance per 1000 die before the 41st birthday. And we would call such a situation "lack of aging." In reality, the 40-year-old has 2 chances for 1000 to die before the 41st birthday. Doubling the risk of death in 20 years is evidence of gradual aging.

Further - worse. The 60-year-old risk of dying is 10 out of 1000, the 80-year-old’s - 60 out of 1000.


Probability of death depending on age

The risk of death does not just grow, but grows with acceleration. Increased wear, or chances of dying every year, as it happens with us after reaching the age of majority, is called "accelerating decrepitude." But other creatures have different laws. The likelihood of death may increase and then level off: “slowing down aging”, or even “death plateaus”. If we choose this definition of aging, we have to say that if the probability of death does not increase, then the species does not grow old. Continuing the trend, even though it sounds strange, one can say that if the probability of death decreases with age, the species is aging the other way round, which is called “negative aging”.

There is another objective measure of aging - a decrease in fertility. Just as mortality is determined by the probability of death, fertility is determined by the probability of reproduction. Men gradually lose fertility with age. In women, this happens faster and drops to zero at the time of menopause. But other species have other patterns and graphs. In some, fecundity grows most of life - another version of “negative aging”.

For example, the Blundinga tortoise , which lives in the American Midwest, is gradually aging for several decades and does not grow, but at the same time increases fertility. Obviously, her risk of death decreases with age. From the point of view of evolution, loss of fertility is the main feature. From the point of view of natural selection, after the loss of fertility, you don’t care that you died.

It is natural for us to classify various species according to their life expectancy, to throw them into a heap of insects that live one day, and to separate them from trees and whales that have lived for hundreds of years. But most of these differences can be attributed to size. Everything from growth and fertility to aging should be slower in hippopotamuses, with a slow metabolism and tons of flesh. Therefore, we are more impressed by a bee that has lived for 20 years than an elk that has lived for 20 years.

But what if you stop looking at life expectancy and compare different species based on form, and not the duration of their life line? Their life is long or short - we will display it on a single scale for comparison. Do not ask how much they live, ask if the population dies gradually, or many of them die in infancy, and then mortality decreases, or all deaths occur near the end of the life cycle. The graph, published in the work of Nature magazine for 2014, is built exactly like this, and it shows the range of nature’s inventiveness very well. All possible combinations are presented, with fast aging, without aging, with reverse aging, and at the same time they can be combined with life cycles of a week, year or century. At the same time, the neighborhood on the charts is completely unexpected. For example, at the top of the chart, with a small mortality rate, which suddenly rises towards the end of life, there are people, nematodes and tropical fish. In terms of the patterns of aging, people are more like nematodes than like chimpanzees.


Dark line - fecundity, light - survival.
person; guppy; chimpanzee; nematode
oak; turtle; Pyrenean Dioscorea; lizard
hydra; Cancer hermit; mouse vole; viburnum

The plots show the variety of ways animals and plants grow old in the wild. The light downward sloping line is a survival curve, and the bold curve below it is fertility. The downward slope of the survival curve means that fewer and more representatives of the species remain alive over time. The graphs are constructed in such a way that a straight line going down diagonally is neutral - that is, it means no aging. Lines with a hump above the diagonal mean normal aging, and lines with a deflection at the bottom - reverse aging, or "negative aging". For example, the line in people remains flat for a long time, and then quickly falls. This means that many people live for a long time, and then their deaths are grouped at the age of 80-90 years (statistics taken from modern Japan).

But in animals and plants in the two lower ranks, mortality is smoother. In turtles and oaks, curves have a reverse bend. This means that in old age they die less often than in youth - this is reverse aging.

The bold line, fecundity, is quite understandable. Fertility may increase with the growth of an animal or a plant, or decrease with reproductive age — for example, in menopause. Note that animals from the top row lose fertility long before death. This is an evolutionary paradox.

In this diagram, if the survival curve looks like a straight diagonal, this means no aging - for example, like that of a hydra and a hermit crab. Hydra is something like a freshwater jellyfish, several millimeters long, and it is found in ponds. All animals in the top row show “real aging” - the likelihood of death increases with age. The next two rows are plants and animals that do not grow old, or grow old vice versa. The older they are, the lower the risk of death. This is true for most trees, and for turtles, as well as for oysters and sharks (which are not represented here).

The fat curve below is fertility. Animals from the top row finish reproduction long before death. This leads us to the evolutionary paradox for Orthodox Darwinists: if the only goal of natural selection is to maximize reproductiveness, why did evolution allow reproductiveness to drop to zero with so many surviving individuals? The rise of fertility curves means an increase in reproduction with age, which is another example of negative aging. When a tree grows larger every year, it is not surprising that it produces more seed. Pyrenean dioscorea is a vine growing on rocky cliffs in the Pyrenees. If she does not interfere, she lives for at least 300 years, with no signs of aging. At the same time, its fertility in the first 20 years is almost zero.

The meaning of graphs is that nature can do anything with aging. Any timeline, any form is possible, and each species has adapted in its own way to the ecological environment. There are no restrictions.

Instant aging

You can age to death quickly and suddenly, at the end of the reproductive cycle. Sudden death after reproduction is often found in nature in such different organisms as mayfly, octopus, salmon, not to mention the thousands of plants that bloom once a year. Biologists call it "semelparnost", from the Latin "one birth".

The causes of death of semelpar organisms are extremely different. Octopuses stop eating. The males of the mantis sacrifice themselves for reproduction, going for a snack to the females. Salmon destroys its body with a steroid release.

By the time the adult salmon reaches the ground for spawning, its metabolism is already in the precollapse stage. The adrenal glands produce steroids (glucocorticosteroids), leading to accelerated, almost instantaneous aging. They stop eating. Steroids lead to a collapse of the immune system, their bodies are covered with fungus. The kidneys atrophy and the neighboring cells grow. The circulation system also suffers. Arteries are damaged in a manner similar to human heart disease. The upstream swim is very heavy, but their bodies are damaged not by mechanical impact. For this is the answer to the cascade of biochemical changes that occurs immediately after reproduction.

Some organisms are genetically programmed to stop eating after reproduction, and die of hunger; it is faster and more reliable than normal aging. They have no mouth or digestive system at all. Elephants chew so many leaves and branches in their lives that they wear out six sets of teeth. But when the sixth set ends, the new one does not grow, and the thick-skinned ones die of hunger.

Longevity

In 2014, photographer Rachel Susman published a photo album with antiquities entitled "The Oldest Living Beings in the World." All this plants. One of the reasons for this is that plants do not need to worry about the muscles of their legs that are strong enough to walk. Being tied to one territory, they can grow and strengthen, grow older and more fertile than any animals, and reap the benefits of age.

Plants have another secret to longevity. In the early stages of an animal’s life, the germ cell line separates from the rest of the body, or soma. Only the germ line needs to be kept intact so that it becomes the next generation. The body can not afford to do so neatly with the soma cells and save on their reproduction. But plants have a different system. Soma and germline are not separated. Plants also have stem cells, and their cells are responsible not only for plant growth, but also for seeds and pollen, which will be the next generation. In the tree, stem cells are located in a thin layer under the bark, the meristem. It spreads to all branches and knots, and leaves grow from it, as well as buds and seeds. Some ginkgo, non-flowering trees, which originated in the Permian period 270 million years ago, can have a meristem of a million years.

But most trees have a certain age, after which the death rate grows every year. Stem shoots begin to grow straight from the trunk, while the growth of branches slows down. There are signs that trees become more vulnerable to fungi and disease as they age, but they are usually ruined by mechanical stress due to excessive size. The very possibility of continuing growth, giving them the property of "reverse aging", leads at the end to their decline.

Aging is the opposite

The medusoid Turritopsis nutricula does not return to kindergarten at the age of 65, but in 2010 it received its 15 minutes of fame when it was called an "immortal jellyfish" in scientific journals. An adult Turritopsis has acquired a cunning trick: having spawned polyps, he regresses back to a polyp, and begins life anew. This is due to the transformation of adult cells back into stem cells, which goes against the usual direction of development, from stem cells to specialized ones. He is driving back down a one-way development street. The headlines wrote about Turritopsis as “The Sea of ​​Benjamin Button”.

Kozheeda beetles (Trogoderma glabrum) perform a similar trick, but only when they are starving. Developing on animal carcasses in the forest, they pass through six different stages of the larvae. At first they look like worms, then like millipedes, then like a water strider to complete the development in the form of six-legged beetles. A couple of entomologists from the University of Wisonson in 1972 isolated the larvae of beetles in the sixth stage of development (when they were ready to become adults) in test flasks and found that without food they returned to the fifth stage. And if they go hungry for many days, they decrease and return further back in stages, until they turn back into the larvae, as if they had just appeared on the world. If you then resume feeding, they go forward through the developmental stages, and become adults, maintaining a normal life expectancy. They are able to repeat this cycle again and again, when scientists feed them to the sixth stage, and then starve them so that they return to the first. The normal life span at eight weeks thus stretched over two years.

Old aging

Hydras are invertebrates with radial symmetry, each has a mouth on a stalk, surrounded by tentacles that grow, if cut off, just like a multi-headed monster from Greek mythology, after whom they were named. They were observed at intervals up to 4 years in a row, starting with instances of different ages caught in nature, and over time they do not die and do not become more vulnerable to predators or diseases. In the human body, special cells, such as blood cells, skin and stomach, die and grow back. In the hydra, this is how the whole body works; it regenerates from the stem cell base every few days. Some cells die off, others, reaching a certain size, turn into clones of the hydra, which bud off from her body. This is an ancient way of reproduction, coping without sex. For hydra, sex is optional - she rarely does it.

A recent article claims that the hydra is aging, and this is evident from the decrease in the cloning rate. The author believes that it is possible that the clones inherit the age of the parent. It is hypothesized that only sexual reproduction nullifies the hours of aging. If this is the case, then hydra aging is a return to protists, hereditary microbes that are more complex than bacteria. Some of them have a limited lifetime, since they can be divided a limited number of times, after which they end up with reproductive gasoline - if they are not restarted using gene exchange (the pro version of the sex version), which restarts their watches. Amoebas and microbes of the genus Paramecium are examples of such protists, single-celled with a long life line, which in antiquity gave rise to more than 100,000 species - algae, slugs, ciliates, and other organisms not belonging to the kingdoms of animals, fungi, plants and bacteria.

Disable aging

In queen bees and worker bees the same genes, but different lifespans. In uterus royal jelly disables aging. When a new hive begins, the feeding bee chooses - as far as we can judge, by chance - one larva that will get a liquid royal diet. A certain physiologically active chemical ambrosia in royal jelly switches the lucky bee into growth mode, and it turns into a queen, and not into a working bee. Milk gives the queen overly developed sex glands, because of what she acquires a characteristic size and shape. The queen makes one flight at the beginning of her career, for which she can mate with a dozen different drones, and keep their sperm for years.

Under the weight of eggs, the adult queen can no longer fly, and becomes a machine for reproduction. She lays 2,000 eggs a day, more than her own weight. Of course, such a machine requires a retinue from the workers serving it to feed, remove waste and transfer pheromones (chemical signals) to the rest of the hive.

Working bees live for several weeks and die of old age. And they do not just wear out from the affected parts of the body that break in the cruel world where they live. Their survival follows a familiar mathematical form, the Gompertz curve is a characteristic survival graph, typical of humans and other animals, indicating aging. But queen bees, although their genes are identical to worker bees, do not show signs of aging. They can live for years, and sometimes, in stable hives, and for decades. They represent wonders without age. The queen dies when she runs out of sperm obtained during the wedding flight. It may continue to lay eggs, but they will be unfertilized and only drones can grow out of them. The same workers who served the queen kill her, surrounding and squeezing her to death.

Life expectancy after the reproductive period

Why is there menopause? We care about young and big families, and our loyalty does not end after the children grow up and become parents themselves. Therefore, the usual explanation for life that continues after fertility ends is called the “grandmother's hypothesis”. Women have a genetic interest in raising healthy grandchildren. Perhaps at the age of 60 they can give more to their genetic heritage by caring for their grandchildren than by giving birth to their children. The hypothesis sounds reasonable, at least for people, but demographic researchers have found that with numbers in their hands it is very difficult to confirm.

Whales and elephants also outlive their fertility. They are also social animals. Perhaps for their grandchildren they are more important than we think. But there are other animals living after their fecundity has been exhausted. Guppies, water fleas, nematodes, rotifers, in comparison with which any idle father looks like Mary Poppins. They lay eggs - that's all. And the wing (or fin) does not move to take care of the young, and even more so - about the grandchildren. And, nevertheless, modern evolutionary theory says that no natural selection makes them live, therefore they must die.

In 2011, Charles Goodnight and I came up with how evolution could lead to life after reproduction. The idea itself is unlikely to sound, but it coincides with the numbers. The old retirement segment of the population is needed to maintain the stability of the population in the cycles of abundance and hunger. In good times, they eat excess food and prevent an overgrowth of the population. When food is scarce, they die first.

The types of aging in nature are as diverse as they are generally possible, suggesting that nature can turn aging on and off at will. Therefore, we can be forgiven for the fact that we with great skepticism consider the theory, speaking about the need for aging. Whatever the theory of aging, we need to be flexible, diverse and not reject exceptions.

– -, . AgingAdvice.org, ScienceBlog.com. MIT, .

– , , . , Natural History, Smithsonian, Wired, New Scientist The New York Times.