ИСТИНА

Abstract In this lecture, I shall consider some physiological mechanisms responsible for longevity of eusocial mammals, i.e. a rodent (naked mole rat) and a primate (human). It is concluded that both naked mole rat and human are no more affected by dynamic natural selection due to specific organization of the socium and substitution of fast technical progress for slow biological evolution, respectively. Since aging is supposed to be a program increasing pressure of natural selection upon an individual, such a program became a harmful atavism for naked mole rat and human. This is apparently why aging as a reason for death is very rare in naked mole rats younger than 30 years and humans younger than 55 years. Such an effect is achieved, at least partially, by prolongation of youth (neoteny). The numerous facts are described indicating that The Master Biological clock responsible for timing of oncogenesis retarded both in naked mole rat and human. In these species numerous traits of youth do not disappear (or disappear enormously slowly) with age. For a long time, in naked mole rat, this point of view was supported mainly by morphological observations, such as absence of hair, auricles and scrotum, underdevelopment of lung, etc. During last decade, numerous physiological features of neoteny in naked mole rat were described. Among them are (i) long gestation, (ii) longer maturity time, (iii) strong delay in brain development, (iv) regeneration and elongation of neurons during entire life span, (v) extremely high resistance of adult mole rat neurons to anoxia/reoxigenation, a property inherent in newborn and young, but not adult mammals, (vi) resistance to H2O2 - induced apoptosis of cell culture, (vii) absence of age-linked decay in levels of antioxidants (in particular, due to very high concentration of extracellular antioxidant hyaluronan), (viii) absence in increase in peroxidation index of lipids with age, (ix) no age-linked increase in ROS production, (x) retarded postnatal development of mitochondrial reticulum in skeletal muscles, (xi) absence of age-linked decay in levels of mitochondria with age, (vi) no age-induced decay in proteasome level, (xii) no indications of aging of immune system, (xiii) low transcription of genes and activity of insulin and IGF1 and high transcription and activity of IGF2, etc. These and other specific physiological features of the naked mole rats explain their resistance to cancer, many infections, cardiovascular and brain diseases, diabetes, and, as a result, their long maximal lifespan, i.e. more than 34 years vs. 3.5 years for mice (a rodent of the similar size as a naked mole rat). For humans, it is generally accepted that embryo, neonatanal and young organisms have features common to other primates, thereby the listed morphs resemble very much human, not ape. As to the ape-specific traits (a lot of hair on the body, construction of the skull, large super ciliary arches, etc.), they appear in adulthood of animals and do not appear in humans. Recently, studies of brain transcriptomes of humans, chimpanzees and rhesus macaques revealed that in humans, just like in naked mole rat, transcription of large group of genes is strongly retarded compared to the great apes. Comparison of pairs of highly and lowly social mammals (naked mole rat vs. mouse and human vs. chimpanzee) is very interesting. In both pairs, highly social representative (i) is long-lived, (ii) its age-dependent mortality during first 30-35 years is so low that its contribution to the total mortality is negligible, (iii) gestation and maturation times are longer, (iv) brain development is strongly retarded but without negative effect on the final mass of the organ, (v) skeletal muscle development is also retarded resulting in lowering in the final mass. Demonstration of neoteny in humans at physiological and genetic levels is very important for understanding of physiological, pathological and therapeutic aspects of aging. In particular, prolongation of youth by delay of aging is impossible to imagine within the framework of the concept of stochastic (non-programmed) aging but can be explained if aging is programed and controlled by The Master Biological Clock, like other main steps of ontogenesis. Arrest of operation of aging program in humans by an antiaging medicine seems to be a promising approach to prolong our healthspan.