In Search of Genes that Were Lost in Longer-Lived Mammals

In Search of Genes that Were Lost in Longer-Lived Mammals

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Researchers here describe an interesting approach to improving the understanding of how differences in species longevity arise from differences in the operation of cellular metabolism. They report on a search for genes in short-lived mammals, mice in this case, that have been lost in long-lived mammals such as our species. Finding such genes can then lead to an investigation of specific aspects of cell and tissue function relevant to life span. As is often the case in this field, the work is of scientific interest, but not really all that relevant to near future efforts to produce rejuvenation. A complete understanding of how exactly aging progresses in detail and which mechanisms are more or less important would be helpful, but it is by no means necessary. The research and development community can forge ahead to repair the known causes of aging without a full understanding of aging – indeed, this is already progressing quite well in the matter of stem cells and senescent cells.

The genetic propensity of certain species for longevity and anti-aging is a challenging problem in vertebrate biology. Of particular interest are the genes that influence life expectancy differences among species. These genes are expected to be the real longevity genes of interest and should explain the wide differences in the rate of aging among diverse species and why similarly sized rodents or primates sometimes have anomalous life expectancies – such as naked mole-rats or humans.

No such genes have been unequivocally identified. We performed a computer-aided analysis of data relevant to lifespan and made a bioinformatic search for the genes, the loss of which might modulate lifespan. This search is based on the general idea that such genes are lost in a predefined set of species but are present in another predefined set of species. Examples of such pairs of sets include long-lived vs short-lived, homeothermic vs poikilothermic, among others. Species are included in one of two sets depending on the property of interest, such as longevity or homeothermy. A bioinformatics method and software relevant to the idea are universal towards these sets and the property that defines them.

Here, the proposed method was applied to study the longevity of Euarchontoglires species. It largely predicted genes that are highly expressed in the testis, epididymis, uterus, mammary glands, and the vomeronasal and other reproduction-related organs. In conclusion, the developed method and its software allowed us to identify a short list of presumably lost genes associated with a long lifespan in Euarchontoglires. The predicted lost genes largely demonstrate specific expressions in reproductive organs, which agrees with Williams’ hypothesis concerning the reallocation of the physiological resources of the body between self-maintenance and reproduction (transition from r-strategy to К-strategy in the species evolution). The loss of some predicted vomeronasal and olfactory receptor genes in human and naked mole-rat conforms to their specific anatomical features. We suggest that the loss of certain genes in evolution is one of the essential determinants of lifespan. Overall, it is a likely driving force for many aspects of species evolution in vertebrates.


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