07 March 2017

Sociality, neoteny and longevity

What do naked diggers and "naked monkeys" have in common?

Alexander Markov, "Elements"


Fig. 1. Young naked diggers (left) and a 30-year–old patriarch - a breeding male (husband of the "queen"). Although it is clear that he has shrunk somewhat with age (sarcopenia and loss of subcutaneous fat are senile signs), he is still cheerful, regularly performs his marital duties and is not going to die at all. Photo from the discussed article in Physiological reviews

Naked diggers and humans differ from their relatives (rodents and primates, respectively) in two rare features: highly developed sociality and longevity. Russian and German biologists have analyzed the facts indicating that these two species of mammals have another important common feature: juvenile (neoteny), that is, developmental delay leading to the preservation of a number of childhood and even embryonic traits in adults. It is possible that all three unusual features of naked diggers and "naked monkeys" – sociality, longevity and neoteny are closely related.

The "Elements" have repeatedly told about naked diggers – amazing eusocial mammals whose existence was predicted Richard Alexander (Richard D. Alexander), a specialist in the evolution of sociality (see: R. Alexander, 1974. The evolution of social behavior), even before the lifestyle of these rodents became known to science.

Naked diggers have a number of unique features (see the links at the end of the news). According to the same Alexander (who seriously started studying naked diggers when it turned out that the eusocial burrowing rodents predicted by him really exist), these animals stand out as sharply among rodents as humans do among primates.

One of the most amazing properties of naked diggers is their longevity. In the laboratory, they can live up to 30 years or more. The limit has not yet been set, because naked diggers have recently been kept in captivity. Other rodents of the same size (a naked digger – animal the size of a mouse) live ten times less. It is not surprising that gerontologists looking for ways to prolong human life have high hopes for the study of naked diggers.

It is not known exactly how long naked diggers live in natural conditions, but this, apparently, strongly depends on their social status. Breeding individuals (the queen and her husbands, which usually happen from one to three) are protected from predators (snakes) and other hardships by the efforts of non-breeding workers and can live for a very long time. The longer they live, the more descendants they will leave. As for the workers, they often die in bloody battles with workers from neighboring colonies, and therefore their average life expectancy seems to be small. However, it must be remembered that in naked diggers, unlike many eusocial insects, working individuals retain a real chance of participating in reproduction. For example, a working female can take the place of a deceased queen (females in such cases desperately fight for the "right to the throne", which eventually goes to the strongest). Thus, in order to leave offspring, you need not only to wait for your chance, but also to keep in good physical shape by the time this chance appears. Therefore, it is possible that it is "beneficial" for a naked digger (from the point of view of the spread of his genes) not to age longer, even if he is not a king and not a queen, but a simple worker. To put it more correctly, the social lifestyle of naked diggers could contribute to selection for delayed aging.

Apparently, the aging process in naked diggers is really slowed down. They don't just live for a long time: many "senile" diseases, the frequency of which increases sharply with age in mice and other mammals (including cancer, diabetes, many cardiovascular and neurological pathologies) are rare in naked diggers and even less likely to cause death. In laboratory conditions, they not only have very low mortality, but there is almost no pronounced increase in mortality with age (which is often equated with the very concept of "aging"). In the laboratory, as in nature, workers die most often in fights with relatives.

The question of what naked diggers and humans have in common at first glance resembles a similar question about a raven and a desk. But this is only at first glance. Humans stand out among primates not only by their highly developed sociality, like naked diggers among rodents, but also by their longevity. According to the AnAge database, the record life expectancy of a chimpanzee is 59.4 years, a human is 122.5 years, that is, twice as long. In addition, in chimpanzees, even under ideal conditions, there is a rapid increase in mortality with age, whereas in modern people in developed societies, mortality under 60 remains low and grows very slowly with age (although then its growth accelerates).

In a review article published in the journal Physiological reviews, a group of Russian and German biologists led by Academician V.P. Skulachev analyzed the facts indicating that naked diggers and "naked monkeys" there is another important common feature. It consists in the fact that both species retain many traits characteristic of young or even embryos of similar species in adulthood.

Individual signs of neoteny in a broad sense (juvenilization, that is, slowing down the development of individual organs and body systems) in naked diggers were previously noted by some authors, starting with Richard Alexander. The novelty of the work under discussion lies in the fact that the authors tried, firstly, to compile the most complete list of neotenic signs in naked diggers, and secondly, to discuss possible cause-and-effect relationships between neoteny, sociality and longevity.

1. Signs of neoteny in naked diggers

Some juvenile features of naked diggers are immediately noticeable – for example, small (compared to the closest relatives) sizes and almost complete absence of hair. Mice are also born hairless, but naked diggers remain like this all their lives. Naked diggers also completely lack auricles (their relatives develop them shortly after birth) and a scrotum, which develops in male rats and mice by the age of three weeks.

Other "childish" traits are found at the molecular and cellular levels. For example, brain neurons in naked diggers are very resistant to anoxia (oxygen starvation). Such resistance is typical for newborn mammals (it helps not to suffocate during childbirth), but it is lost with age. Naked diggers keep it for life. Resistance is partly associated with increased expression of a gene encoding one of the glutamate receptor subunits (GluN2D). In mice, its expression is increased in newborns and decreases rapidly with age, in naked diggers, it remains high throughout life.

In the development and work of the brain of naked diggers, many other embryonic and childhood signs were found (including the active formation of new neurons – neurogenesis and the preservation of a high level of plasticity), which indicates a general juvenile brain and largely explains the resistance of naked diggers to "senile" neurodegenerative processes (O. K. Penz et al., 2015. Extracted brain development in a rodent model of extreme longevity).

Signs such as a long pregnancy (66-84 days versus 20 days in the mouse) and the late onset of puberty also indicate a slowdown in development. Female mice begin to breed at the age of one and a half months, and female naked diggers – at the earliest at 7.5 months, and usually later (up to 16 years) – depending on when they manage to take the place of the "queen". Fertility in most mammals is maximal at the beginning of adulthood and decreases with age, while in naked diggers it increases.

The level of the most important antioxidant enzyme of mitochondria, superoxide dismutase 2, decreases with age in mice, but not in naked diggers. This is also true for other enzymes with similar functions (superoxide dismutase 1, catalase). Moreover, naked diggers, unlike other mammals, do not increase the level of free radicals in mitochondria with age. The cells of naked diggers are more resistant to oxidants such as H2O2. All this may be directly related to the delay in aging (see: Free Radical theory of aging).

Another juvenile trait of naked diggers is a weak ability to maintain a constant body temperature, which is typical for newborn mammals. Signs of juvenilization and delayed development (including delayed aging) are also noted in the structure of the lungs, bones, blood vessels, mitochondria of skeletal muscles, in the work of signaling systems affecting life expectancy with the participation of insulin and insulin-like growth factor 1 (M. Barbieri et al., 2003. Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans), etc. The list of neotenic features of naked diggers given in the article has a total of 43 items. These data are in good agreement with the assumption that naked diggers are neotenic animals, in which, in comparison with other rodents, many ontogenetic processes, including aging, are slowed down.

2. Signs of neotenia in humans

It has long been noticed that for a number of signs, people look more like baby monkeys than adults. Apparently, in the course of anthropogenesis, our ancestors underwent juvenilization, which affected not only many morphological features (Fig. 2), but also features of the brain and behavior. In particular, it is assumed that selection for reduced intra-group aggression (a "childish" trait in many mammals), which occurred at the early stages of anthropogenesis, could simultaneously lead to the juvenilization of a number of other traits, just as it happened with domesticated foxes in the famous experience of D. K. Belyaev (see: L. N. Trut, 2007. Will a person find a new friend?).


Fig. 2. The skull of an adult male (left) is more similar in a number of ways to the skull of a baby chimpanzee (center) than an adult male (right). Photos from websites boneclones.com, boneclones.com, rafael.glendale.edu

Long-known facts about the delayed development of a number of signs in humans compared to other monkeys (see: L. Bolk, 1925. On the Problem ot Anthropogenesis) have recently been supplemented with the most important array of information on gene expression in the brain. A comparison of the nature of age-related changes in the expression of many key genes associated with the development of the neocortex and synaptic plasticity in humans and other monkeys led researchers to the conclusion of "transcriptional neoteny" of the human brain (M. Somel et al., 2009. Transcriptional neoteny in the human brain). As in the naked digger compared to other rodents, at the molecular and cellular level, the development of the human brain was greatly stretched over time compared to chimpanzees and macaques. In particular, the maximum expression of genes associated with synapse formation in the prefrontal cortex in chimpanzees and macaques is observed at the age of one year, and in humans at five years (X. L. Liu et al., 2012. Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques).

On the one hand, it is obvious that the time-stretched development of the human brain is associated with its large volume and with the difficulty of passing large-headed cubs through the birth canal. On the other hand, this does not negate the fact that there is a slowdown in ontogenetic processes (including the postponement of the moment of cessation of brain growth), that is, neoteny in the broad sense. In addition, let's not forget that a similar slowdown is characteristic of the naked digger (see above), although the final volume of his brain is about the same as that of a mouse.

Thus, the old idea that a number of ontogenetic processes slowed down during anthropogenesis is confirmed by new data.

3. Sociality, neoteny and longevity: is there a connection between them?

So, naked diggers and humans are united, in addition to longevity and exceptionally highly developed sociality, also numerous neotenic traits. Is this a coincidence? Or is there really a connection between these three features?

The correlation between neoteny and long life seems quite natural. Although we still know little about the genetic mechanisms of regulating the pace of development (in particular, it is unclear whether there are some single "ontogenetic clock" or the rate of development is controlled by different molecular systems at different stages), it is more or less obvious that the timing of the development of different subsystems of the organism and stages of ontogenesis – if not all, then at least some – may be interconnected. Therefore, slowing down some processes may automatically lead to slowing down others. For example, selection for delayed aging can lead, as a side effect, to a delay in the development of the neocortex and hairline. Or vice versa: selection for the delayed development of some organ can lead to a general slowdown in ontogenesis and prolongation of life. After all, aging is a natural stage of the life cycle that depends on genes and is "programmed" in the genome in the same way as other ontogenetic processes (regardless of whether aging is an adaptation supported by selection or a side effect of weakening selection with age, see below). In addition, it can be assumed that if selection simultaneously supports the slowing down of several ontogenetic processes at once (for example, delayed brain development – so that children are not born with too big heads and learn better in childhood, and delayed aging – due to the increased role of grandparents in caring for offspring), then in such a situation, the probability of the formation of a whole complex of neotenic changes increases. Thus, it is possible that neoteny and longevity were acquired by naked diggers and humans in a single complex, as two interrelated traits.

What connection can there be between neoteny/longevity and highly developed sociality? Let's consider two alternative hypotheses. The first of them is mentioned in the article under discussion and is based on the idea that aging is an adaptation for the benefit of a group (or population) that increases the adaptability of organisms. This idea was first expressed by another August Weisman, and although most modern gerontologists reject it, V. P. Skulachev is its staunch and consistent supporter. According to Skulachev, aging increases the efficiency of natural selection and therefore benefits the population in the long term (see: Academician Skulachev's hypothesis). Aging as a trait harmful to the individual, but useful for the group, can be supported by such forms of selection as group selection, kin selection or "second-order selection for evolutionary prospects", the reality of which was demonstrated in a long-term evolutionary experiment by Richard Lenski.

Within the framework of the idea of adaptive aging, the link between longevity and sociality is explained by the fact that sociality in humans and naked diggers sharply weakens the effect of natural selection, and therefore it becomes meaningless to grow old in order to increase its effectiveness. In the case of diggers, the weakening of selection is due to the fact that numerous workers who do not reproduce themselves and therefore do not participate in the evolutionary process, reliably protect the queen and her husbands from all adversity. In addition to the protection of people, the fact that adaptation to a changeable environment is now coming at the expense of cultural, social, scientific and technological development, and not at the expense of biological evolution. Natural selection becomes irrelevant, aging as a way to increase its effectiveness loses its meaning, and the "genetic program of aging" degrades.

An alternative explanation can be given within the framework of the so-called "classical evolutionary theory of aging", which is based on the idea of the weakening of natural selection with age (see: Evolution of aging). Even an ageless organism, the viability of which does not depend on age, is not immortal: sooner or later it will still die because of a predator, disease or natural disaster. The probability of surviving to the age of X in an ageless organism decreases exponentially as X grows . The lower the probability of survival to a given age, the weaker the effect of selection on mutations whose phenotypic effect manifests itself at that age or later. This implies the inevitability of the accumulation of harmful mutations with late effects, which become the cause of aging. In addition, there are alleles that increase viability or fertility at an early age at the cost of an accelerated decrease in viability with age. Such alleles spread because their early phenotypic effects are "more important" for selection (they have a stronger effect on integral fitness) than the later ones.

The "classical evolutionary theory of aging" predicts that increased mortality caused by external causes (for example, predators or floods), especially indiscriminate (independent of the state of the organism), should contribute to the evolution of accelerated aging and the shift of reproduction to an early age (the strategy of "live fast, die young"). At the same time, the late stages of the life cycle, to which almost no one survives due to high external mortality, atrophy under the load of mutations, like an unused organ. Conversely, a decrease in external non-selective mortality should contribute to the evolution of delayed aging and prolongation of life, that is, a decrease in "internal" mortality. After all, now individuals have a chance to live to a respectable age, which means that mutations that reduce late fitness cease to be invisible to selection and begin to be culled. These ideas are detailed in the classic work of George Williams (G. C. Williams, 1957. Pleiotropy, Natural Selection, and the Evolution of Senescence).

From this point of view, sociality in both naked diggers and humans can contribute to longevity simply because it makes life more secure and reduces non-selective exogenous mortality, thereby contributing to selection for longevity. For example, a mouse with a mutation that slows down aging is unlikely to leave more descendants than a mouse without a mutation. After all, both of them are likely to be eaten by someone long before the age when mice begin to weaken from old age. It's quite another matter if you are the queen of naked diggers, sitting in a secure underground shelter surrounded by an army of loyal defenders. In this case, you have a good chance to live a long and fruitful life, and the longer you can resist old age, the more descendants you will leave. Thus, within the framework of this model, we assume that sociality does not weaken, but on the contrary, strengthens the effect of selection – at least on signs that manifest themselves at a late age. As for other neotenic traits, they may develop as a side effect of selection on longevity if evolution follows the path of a general slowdown in ontogenesis, or they may have their own adaptive value.

Which of these explanations is closer to reality, future research will show.

A source:  Skulachev et al., Neoteny, Prolongation of Youth: From Naked Mole Rats to “Naked Apes” (Humans) // Physiological Reviews. 2017. V. 97. P. 699–720.

Portal "Eternal youth" http://vechnayamolodost.ru  07.03.2017

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