Evolution of Longevity in Tetrapods: Safety Is More Important than Metabolism Level.

Various environmental morphological and behavioral factors can determine the longevity of representatives of various taxa. Long-lived species develop systems aimed at increasing organism stability, defense, and, ultimately, lifespan. Long-lived species to a different extent manifest the factors favoring longevity (gerontological success), such as body size, slow metabolism, activity of body's repair and antioxidant defense systems, resistance to toxic substances and tumorigenesis, and presence of neotenic features. In continuation of our studies of mammals, we investigated the characteristics that distinguish long-lived ectotherms (crocodiles and turtles) and compared them with those of other ectotherms (squamates and amphibians) and endotherms (birds and mammals). We also discussed mathematical indicators used to assess the predisposition to longevity in different species, including standard indicators (mortality rate, maximum lifespan, coefficient of variation of lifespan) and their derivatives. Evolutionary patterns of aging are further explained by the protective phenotypes and life history strategies. We assessed the relationship between the lifespan and various studied factors, such as body size and temperature, encephalization, protection of occupied ecological niches, presence of protective structures (for example, shells and osteoderms), and environmental temperature, and the influence of these factors on the variation of the lifespan as a statistical parameter. Our studies did not confirm the hypothesis on the metabolism level and temperature as the most decisive factors of longevity. It was found that animals protected by shells (e.g., turtles with their exceptional longevity) live longer than species that have poison or lack such protective adaptations. The improvement of defense against external threats in long-lived ectotherms is consistent with the characteristics of long-lived endotherms (for example, naked mole-rats that live in underground tunnels, or bats and birds, whose ability to fly is one of the best defense mechanisms).

Motus Vita Est: Fruit Flies Need to Be More Active and Sleep Less to Adapt to Either a Longer or Harder Life.

BACKGROUND: Activity plays a very important role in keeping bodies strong and healthy, slowing senescence, and decreasing morbidity and mortality. Drosophila models of evolution under various selective pressures can be used to examine whether increased activity and decreased sleep duration are associated with the adaptation of this nonhuman species to longer or harder lives. METHODS: For several years, descendants of wild flies were reared in a laboratory without and with selection pressure. To maintain the "salt" and "starch" strains, flies from the wild population (called "control") were reared on two adverse food substrates. The "long-lived" strain was maintained through artificial selection for late reproduction. The 24 h patterns of locomotor activity and sleep in flies from the selected and unselected strains (902 flies in total) were studied in constant darkness for at least, 5 days. RESULTS: Compared to the control flies, flies from the selected strains demonstrated enhanced locomotor activity and reduced sleep duration. The most profound increase in locomotor activity was observed in flies from the starch (short-lived) strain. Additionally, the selection changed the 24 h patterns of locomotor activity and sleep. For instance, the morning and evening peaks of locomotor activity were advanced and delayed, respectively, in flies from the long-lived strain. CONCLUSION: Flies become more active and sleep less in response to various selection pressures. These beneficial changes in trait values might be relevant to trade-offs among fitness-related traits, such as body weight, fecundity, and longevity.

Evolution of Longevity as a Species-Specific Trait in Mammals.

From the evolutionary point of view, the priority problem for an individual is not longevity, but adaptation to the environment associated with the need for survival, food supply, and reproduction. We see two main vectors in the evolution of mammals. One is a short lifespan and numerous offspring ensuring reproductive success (r-strategy). The other one is development of valuable skills in order compete successfully (K-strategy). Species with the K-strategy should develop and enhance specific systems (anti-aging programs) aimed at increasing the reliability and adaptability, including lifespan. These systems are signaling cascades that provide cell repair and antioxidant defense. Hence, any arbitrarily selected long-living species should be characterized by manifestation to a different extent of the longevity-favoring traits (e.g., body size, brain development, sociality, activity of body repair and antioxidant defense systems, resistance to xenobiotics and tumor formation, presence of neotenic traits). Hereafter, we will call a set of such traits as the gerontological success of a species. Longevity is not equivalent to the evolutionary or reproductive success. This difference between these phenomena reaches its peak in mammals due to the development of endothermy and cephalization associated with the cerebral cortex expansion, which leads to the upregulated production of oxidative radicals by the mitochondria (and, consequently, accelerated aging), increase in the number of non-dividing differentiated cells, accumulation of the age-related damage in these cells, and development of neurodegenerative diseases. The article presents mathematical indicators used to assess the predisposition to longevity in different species (including the standard mortality rate and basal metabolic rate, as well as their derivatives). The properties of the evolution of mammals (including the differences between modern mammals and their ancestral forms) are also discussed.

Coevolution of Brain, Culture, and Lifespan: Insights from Computer Simulations.

Humans possess a number of traits that are rare or absent in other primates, including large brain size, culture, language, extended lifespan (LS), and long post-reproductive period. Here, we use a computer model, TribeSim, originally designed to explore the autocatalytic coevolution of the hominin brain and culture within the framework of the "cultural drive" theory, to find out how culture and brain could coevolve with LS (or aging rate). We show that in the absence of culture, the evolution of LS depends on the intensity of the between-group competition (BGC): strong BGC results in shorter LS. Culture, however, favors genetic evolution of longer LS even if the BGC is strong. Extended LS, in turn, enhances cultural development, thus creating positive feedback. Cultural evolution of LS (accumulation of survival-enhancing or survival-impairing knowledge) differs from the genetic evolution of the same trait, partially because "memes" (ideas, skills, and behaviors) that reduce the risk of death tend to spread in the meme pool even if it is not beneficial to genes. Consequently, cultural evolution of aging tends to result in longer LS than genetic evolution of the same trait. If LS evolves both genetically and culturally, the typical result is a society in which young individuals, due to their genetic predisposition, lead a riskier lifestyle in exchange for a chance to gain additional resources, but accumulate survival-enhancing knowledge with age. Simulations also showed that cultural evolution of adaptive behaviors can contribute to the genetic evolution of a long post-reproductive period, e.g., if the presence of knowledgeable long-livers increases the competitiveness of the group.

Altruism and Phenoptosis as Programs Supported by Evolution.

Phenoptosis is a programmed death that has emerged in the process of evolution, sometimes taking the form of an altruistic program. In particular, it is believed to be a weapon against the spread of pandemics in the past and an obstacle in fighting pandemics in the present (COVID). However, on the evolutionary scale, deterministic death is not associated with random relationships (for example, bacteria with a particular mutation), but is a product of higher nervous activity or a consequence of established hierarchy that reaches its maximal expression in eusocial communities of Hymenoptera and highly social communities of mammals. Unlike a simple association of individuals, eusociality is characterized by the appearance of non-reproductive individuals as the highest form of altruism. In contrast to primitive programs for unicellular organisms, higher multicellular organisms are characterized by the development of behavior-based phenoptotic programs, especially in the case of reproduction-associated limitation of lifespan. Therefore, we can say that the development of altruism in the course of evolution of sociality leads in its extreme manifestation to phenoptosis. Development of mathematical models for the emergence of altruism and programmed death contributes to our understanding of mechanisms underlying these paradoxical counterproductive (harmful) programs. In theory, this model can be applied not only to insects, but also to other social animals and even to the human society. Adaptive death is an extreme form of altruism. We consider altruism and programmed death as programmed processes in the mechanistic and adaptive sense, respectively. Mechanistically, this is a program existing as a predetermined chain of certain responses, regardless of its adaptive value. As to its adaptive value (regardless of the degree of "phenoptoticity"), this is a characteristic of organisms that demonstrate high levels of kinship, social organization, and physical association typical for higher-order individuals, e.g., unicellular organisms forming colonies with some characteristics of multicellular animals or colonies of multicellular animals displaying features of supraorganisms.

A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3.

This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2 enables stress adaptation by activating cell antioxidant defense and other metabolic processes via control of expression of over 200 target genes in response to various types of stress. The GSK3 system represents a "regulating valve" that controls fine oscillations in the Nrf2 level, unlike Keap1, which prevents significant changes in the Nrf2 content in the absence of oxidative stress and which is inactivated by the oxidative stress. Furthermore, GSK3 modifies core circadian clock proteins (Bmal1, Clock, Per, Cry, and Rev-erbα). Phosphorylation by GSK3 leads to the inactivation and degradation of circadian rhythm-activating proteins (Bmal1 and Clock) and vice versa to the activation and nuclear translocation of proteins suppressing circadian rhythms (Per and Rev-erbα) with the exception of Cry protein, which is likely to be implicated in the fine tuning of biological clock. Functionally, GSK3 appears to be one of the hubs in the cross-regulation of circadian rhythms and antioxidant defense. Here, we present the data on the crosstalk between the most powerful cell antioxidant mechanism, the Nrf2 system, and the biorhythm-regulating system in mammals, including the impact of GSK3 overexpression and knockout on the Nrf2 signaling. Understanding the interactions between the regulatory cascades linking homeostasis maintenance and cell response to oxidative stress will help in elucidating molecular mechanisms that underlie aging and longevity.

Runaway brain-culture coevolution as a reason for larger brains: Exploring the "cultural drive" hypothesis by computer modeling.

Scale and tempo of brain expansion in the course of human evolution implies that this process was driven by a positive feedback. The "cultural drive" hypothesis suggests a possible mechanism for the runaway brain-culture coevolution wherein high-fidelity social learning results in accumulation of cultural traditions which, in turn, promote selection for still more efficient social learning. Here we explore this evolutionary mechanism by means of computer modeling. Simulations confirm its plausibility in a social species in a socio-ecological situation that makes the sporadic invention of new beneficial and cognitively demanding behaviors possible. The chances for the runaway brain-culture coevolution increase when some of the culturally transmitted behaviors are individually beneficial while the others are group-beneficial. In this case, "cultural drive" is possible under varying levels of between-group competition and migration. Modeling implies that brain expansion can receive additional boost if the evolving mechanisms of social learning are costly in terms of brain expansion (e.g., rely on complex neuronal circuits) and tolerant to the complexity of information transferred, that is, make it possible to transfer complex skills and concepts easily. Human language presumably fits this description. Modeling also confirms that the runaway brain-culture coevolution can be accelerated by additional positive feedback loops via population growth and life span extension, and that between-group competition and cultural group selection can facilitate the propagation of group-beneficial behaviors and remove maladaptive cultural traditions from the population's culture, which individual selection is unable to do.

Perspectives of Homo sapiens lifespan extension: focus on external or internal resources?

Homo sapiens and naked mole rats (Heterocephalus glaber) are vivid examples of social mammals that differ from their relatives in particular by an increased lifespan and a large number of neotenic features. An important fact for biogerontology is that the mortality rate of H. glaber (a maximal lifespan of more than 32 years, which is very large for such a small rodent) negligibly grows with age. The same is true for modern people in developed countries below the age of 60. It is important that the juvenilization of traits that separate humans from chimpanzees evolved over thousands of generations and millions of years. Rapid advances in technology resulted in a sharp increase in the life expectancy of human beings during the past 100 years. Currently, the human life expectancy has exceeded 80 years in developed countries. It cannot be excluded that the potential for increasing life expectancy by an improvement in living conditions will be exhausted after a certain period of time. New types of geroprotectors should be developed that protect not only from chronic phenoptosis gradual poisoning of the body with reactive oxygen species (ROS) but also from acute phenoptosis, where strong increase in the level of ROS immediately kills an already aged individual. Geroprotectors might be another anti-aging strategy along with neoteny (a natural physiological phenomenon) and technical progress.

Does adaptation to different diets result in assortative mating? Ambiguous results from experiments on Drosophila.

The emergence of behavioural isolation between populations under divergent selection can be crucial for ecological speciation, but the mechanisms underlying such isolation are poorly understood. Several experimental evolution studies have shown that positive assortative mating (preference for similar mates) can arise rapidly in Drosophila laboratory populations reared in different stressful conditions, while other studies failed to confirm this effect. Here, we present the results of an evolution experiment in which outbred lines of Drosophila melanogaster were reared for 1-2 years on one of the three different diets (standard, starch based or high salt). We show that nonrandom mating arose in some, but not all lines, and that the manifestations and possible interpretations of this nonrandomness depend strongly on the type of tests used to assess mating preferences. More specifically, multiple-choice four-fly tests revealed positive assortative mating (prevalence of homogamic matings) in some starch-adapted and salt-adapted lines when paired with a control line reared on the standard diet, but competitive three-fly tests rather revealed competitive advantage of control males and females over the flies reared on stressful diets. The results imply that divergent adaptation can result in differences in mating propensity or competitive ability, which, in turn, may either facilitate or hamper speciation depending on the relative frequency of high- vs. low-competition settings in natural habitats of the diverging populations. The results also emphasize the importance of using diverse tests for assessing mating structure in natural and laboratory populations.

Neoteny, Prolongation of Youth: From Naked Mole Rats to "Naked Apes" (Humans).

It has been suggested that highly social mammals, such as naked mole rats and humans, are long-lived due to neoteny (the prolongation of youth). In both species, aging cannot operate as a mechanism facilitating natural selection because the pressure of this selection is strongly reduced due to 1) a specific social structure where only the "queen" and her "husband(s)" are involved in reproduction (naked mole rats) or 2) substituting fast technological progress for slow biological evolution (humans). Lists of numerous traits of youth that do not disappear with age in naked mole rats and humans are presented and discussed. A high resistance of naked mole rats to cancer, diabetes, cardiovascular and brain diseases, and many infections explains why their mortality rate is very low and almost age-independent and why their lifespan is more than 30 years, versus 3 years in mice. In young humans, curves of mortality versus age start at extremely low values. However, in the elderly, human mortality strongly increases. High mortality rates in other primates are observed at much younger ages than in humans. The inhibition of the aging process in humans by specific drugs seems to be a promising approach to prolong our healthspan. This might be a way to retard aging, which is already partially accomplished via the natural physiological phenomenon neoteny.

Evolutionary consequences of polyploidy in prokaryotes and the origin of mitosis and meiosis.

BACKGROUND: The origin of eukaryote-specific traits such as mitosis and sexual reproduction remains disputable. There is growing evidence that both mitosis and eukaryotic sex (i.e., the alternation of syngamy and meiosis) may have already existed in the basal eukaryotes. The mating system of the halophilic archaeon Haloferax volcanii probably represents an intermediate stage between typical prokaryotic and eukaryotic sex. H. volcanii is highly polyploid, as well as many other Archaea. Here, we use computer simulation to explore genetic and evolutionary outcomes of polyploidy in amitotic prokaryotes and its possible role in the origin of mitosis, meiosis and eukaryotic sex. RESULTS: Modeling suggests that polyploidy can confer strong short-term evolutionary advantage to amitotic prokaryotes. However, it also promotes the accumulation of recessive deleterious mutations and the risk of extinction in the long term, especially in highly mutagenic environment. There are several possible strategies that amitotic polyploids can use in order to reduce the genetic costs of polyploidy while retaining its benefits. Interestingly, most of these strategies resemble different components or aspects of eukaryotic sex. They include asexual ploidy cycles, equalization of genome copies by gene conversion, high-frequency lateral gene transfer between relatives, chromosome exchange coupled with homologous recombination, and the evolution of more accurate chromosome distribution during cell division (mitosis). Acquisition of mitosis by an amitotic polyploid results in chromosome diversification and specialization. Ultimately, it transforms a polyploid cell into a functionally monoploid one with multiple unique, highly redundant chromosomes. Specialization of chromosomes makes the previously evolved modes of promiscuous chromosome shuffling deleterious. This can result in selective pressure to develop accurate mechanisms of homolog pairing, and, ultimately, meiosis. CONCLUSION: Emergence of mitosis and the first evolutionary steps towards eukaryotic sex could have taken place in the ancestral polyploid, amitotic proto-eukaryotes, as they were struggling to survive in the highly mutagenic environment of the Early Proterozoic shallow water microbial communities, through the succession of the following stages: (1) acquisition of high-frequency between-individual genetic exchange coupled with homologous recombination; (2) acquisition of mitosis, followed by rapid chromosome diversification and specialization; (3) evolution of homolog synapsis and meiosis. Additional evidence compatible with this scenario includes mass acquisition of new families of paralogous genes by the basal eukaryotes, and recently discovered correlation between polyploidy and the presence of histones in Archaea. REVIEWER: This article was reviewed by Eugene Koonin, Uri Gophna and Armen Mulkidjanian. For the full reviews, please go to the Reviewers' comments section.

A fully automatable enzymatic method for DNA extraction from plant tissues.

BACKGROUND: DNA extraction from plant tissues, unlike DNA isolation from mammalian tissues, remains difficult due to the presence of a rigid cell wall around the plant cells. Currently used methods inevitably require a laborious mechanical grinding step, necessary to disrupt the cell wall for the release of DNA. RESULTS: Using a cocktail of different carbohydrases, a method was developed that enables a complete digestion of the plant cell walls and subsequent DNA release. Optimized conditions for the digestion reaction minimize DNA shearing and digestion, and maximize DNA release from the plant cell. The method gave good results in 125 of the 156 tested species. CONCLUSION: In combination with conventional DNA isolation techniques, the new enzymatic method allows to obtain high-yield, high-molecular weight DNA, which can be used for many applications, including genome characterization by AFLP, RAPD and SSR. Automation of the protocol (from leaf disks to DNA) is possible with existing workstations.

Specific xyloglucanases as a new class of polysaccharide-degrading enzymes.

Three specific xyloglucanases (XGs) were isolated from Aspergillus japonicus (32 kDa, pI 2.8), Chrysosporium lucknowense (78 kDa, pI 3.8) and Trichoderma reesei (75-105 kDa, pI 4.1-4.3). The characteristic feature of these enzymes was their high specific activity toward tamarind xyloglucan, whereas the activity against carboxymethylcellulose (CMC) and barley beta-glucan was absent or very low. Peptide mass fingerprinting using MALDI-TOF mass spectrometry showed that the T. reesei XG represents Cel74A, whose gene has been discovered recently (GenBank accession no. AY281371 ), but the enzyme has not been characterized and described elsewhere. Tryptic peptides from A. japonicus and C. lucknowense xyloglucanases did not show any identity to those from known glycoside hydrolases. All enzymes produced XXXG, XXLG/XLXG and XLLG oligosaccharides as the end products of xyloglucan hydrolysis. A. japonicus XG displayed an endo-type of attack on the polymeric substrate, while the mode of action of two other xyloglucanases was similar to the exo-type, when oligosaccharides containing four glucose residues in the main chain were split off the ends of xyloglucan molecules. These results together with growing literature data allow concluding that specific xyloglucanases may represent a new class of glycoside hydrolases, which are different from regular endo-1,4-beta-glucanases.