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== Affiliations ==
Belozersky Inst Physico-Chemical Biol, Lomonosov Moscow State Univ, Moscow, Russia. - firstname.lastname@example.org.
== Abstract continued ==
For several years, our group has been studying the role of mitochondria and mitochondrial reactive oxygen species (mROS) in aging program of mammals. Naked mole rat represents the most interesting model to study aging of mammals. This rodent is as small as a mouse but lives at least 10 times longer. For a naked mole rat, cancer, cardiovascular and brain pathologies, diabetes, infections and other aging-stimulated diseases are absent from the list of reasons of death, mortality is very low and age-independent, fertility seems to not decrease with age. E. Rüppell, who discovered naked mole rats, stressed that its adult form resembles in some aspects newborn rodents of the same ''Bathyergidae'' family, being much smaller and having, like newborn rodents, no fur, auricles and scroptum. Later some other features typical to newborn mammals were also revealed, i.e. inability to maintain stable body temperature below thermoneutrality, underdevelopment of vomeronasal organ, low expression of insulin and IGF1 and high expression of IGF2 genes. FAS – activated proinflammatory serine/threonine kinase (FASTK) is absent from naked mole rat. This suggests that “inflammoaging” is suppressed in these animals. mROS seem to play a key role in aging: O<sub>2</sub> → mROS → H<sub>2</sub>O<sub>2</sub> → apoptosis, necrosis → decrease in cellularity of organs → decay of functions. It was found that extracellular concentration of potent antioxidant hyaluronan is very high in naked mole rat cell cultures, which explains (a) why added H<sub>2</sub>O<sub>2</sub> fails to induce apoptosis of these cultures and (b) very high resistance of hippocampal neurons of naked mole rat to anoxia / reoxygenation. Experiments performed by our group in cooperation with the group of Th. Hildebrandt (Berlin) showed that heart mitochondria from naked mole rat (i) contain lower concentration of adenine nucleotides and (ii) respire much faster after exhaustion of added ADP than before ADP addition. The effect (ii) might be regarded as a mechanism lowering mROS generation. Both, effect (i) and (ii), are inherent in mitochondria from embryo and neonatal rodents . In general, longevity of naked mole rats can be considered as the precedent of neoteny, i.e. extension of youth and delay of aging, a phenomenon known in amphibian (the axolotl / salamander case).
Neotenic aspect of human ontogenesis was investigated since 1926 when L. Bolk suggested that this process differ from ape ontogenesis by extension of childhood and youth. The main argument in favor of such a possibility consisted in that ape embryos and young apes resemble humans much more than apes. In other words, apes are brutalized from a human-like child when they are transformed from young to adult. The following neotenic traits were found to be inherent in the adult humans and young apes but not in adult apes: relatively large skull, thin skull bones, small fangs, flattered and broadened face, ear shape, small nose, hairless body, absence of baculum, short limbs compared to torso, longer legs compared to arms, smaller mass of skeletal muscles. An important discovery was recently made by Ph. Khaitovich and coworkers. The authors showed that initiation of transcription of a large group of genes encoding proteins of prefrontal brain cortex in prenatal and early postnatal periods occurs much later in humans than in chimpanzee and rhesus macaques. Among these genes, there are those encoding synaptic proteins. Nevertheless, the size of the adult brain is larger in humans than in apes. Finally, humans become much more developed in cognitive aspects but underdeveloped in such aspects as physical (muscular) force. In particular, construction of some parts of skeleton (e.g. feet) is clearly more primitive in humans than in apes, as if the common ancestor of humans and apes was more human-like than ape-like. Curves of mortality vs. age for humans start at extremely low mortality in youth (it is much lower than for young apes). However, in elderly, the human mortality values eventually become higher than for apes. An impression arises that in humans a mechanism controlling results of operation of aging program stimulates this program in the end of our life.
In conclusion, extension 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 .
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