From mouse to whale
How to look for longevity genes
How to learn to live longer? Geneticists usually look for an answer to this question by studying individual species or groups of related mammalian species that differ in short or long life. But to understand the universal mechanisms of longevity, a broader approach is needed.
The average life expectancy of a person is steadily increasing and today reaches 70-80 years or more in developed countries. However, only very few cross the centenary line. Nevertheless, this is not a bad achievement for mammals. The record in this regard belongs to bowhead whales: their life expectancy, estimated on the basis of changes in the lens of the eye, is more than 200 years. But representatives of "small" species – for example, shrews or mouse–like rodents - live, if lucky, for a few years. Although in this size group there are such phenomena as some bats or a naked digger, whose life is an order of magnitude longer.
From the point of view of evolution, the main reason for such radical differences in life expectancy is the ecological specialization of animals. It is believed that species living in trees, underground or having a large body mass live longer: all these features make them less vulnerable to predators. In other words, longevity is one of the survival strategies of species, while very "expensive".
Along with such a wide interspecific variability, there is another one – intraspecific. As we know, different individuals of the same species can live more or less, but the scope of these fluctuations is no longer so great. This is important because the genetics of longevity is usually studied by comparing individual genomes within a species. In humans, for example, the emphasis is on studying the genomes of centenarians, but with this approach we will be able to understand only a small part of the huge variability in life spans.
It is possible to come much closer to understanding the general mechanisms of longevity if we study them in different species. Some molecular pathways involved in these mechanisms are already known: the signaling pathway of insulin and insulin-like growth factor, the telomere-telomerase system, wound healing mechanisms, etc.
Recently, Spanish scientists examined the genomes of 57 mammalian species with different lifespans and found more than 2.7 thousand point mutations in 2 thousand genes that distinguish long-lived and short-lived species. These genes are related to the work of such important elements of the body's life support as the DNA repair system, immune and inflammatory reactions, the blood clotting system, as well as mechanisms for maintaining the stability of protein molecules.
The article Farré et al Comparative Analysis of Mammalian Genomes Reveals Key Genomic Variability for Human Life Span is published in the journal Molecular Biology and Evolution – VM.
The latter mechanism seems to be one of the key ones in the aging process. In all mammals, after reaching a certain age, proteins lose structural stability and perform their functions worse, which contributes to a general physiological decline. But for each species, this process goes at a different speed.
Now researchers have found that in long-lived animal species, proteins are indeed much more stable due to the accumulation of a number of mutations that caused certain changes in their amino acid sequences. In addition, four genes have been identified (TOR2A, ADCY7, CDK12 and SPAG16) encoding proteins whose rate of evolution is directly related to life expectancy.
Such works confirm the good practical potential of the evolutionary approach to the study of medical problems associated with aging, and the data obtained with its help can be used in the development of therapy for "age-related" diseases.
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