On the Genetic Determination of Longevity

In one sense, genes absolutely determine longevity. That is the case when we look at differences in species life span. Those differences have their origin in the genome. In another sense genes do not seem to be all that important, when it comes longevity differences within a species. The more that researchers dig into growing vaults of genomic data, the lower their estimated contribution of genetic variants to human life expectancy becomes. Cultural and lifestyle choice differences appear to be a much better explanation for human lineages exhibiting exceptional longevity than inherited genetic variants.

Aging is a complex process indicated by low energy levels, declined physiological activity, stress induced loss of homeostasis leading to the risk of diseases and mortality. Recent developments in medical sciences and an increased availability of nutritional requirements has significantly increased the average human lifespan worldwide. Several environmental and physiological factors contribute to the aging process. However, about 40% human life expectancy is inherited among generations, many lifespan associated genes, genetic mechanisms and pathways have been demonstrated during last decades.

In the present review, we have evaluated many human genes and their non-human orthologs established for their role in the regulation of lifespan. The study has included more than fifty genes reported in the literature for their contributions to the longevity of life. Intact genomic DNA is essential for the life activities at the level of cell, tissue, and organ. Nucleic acids are vulnerable to oxidative stress, chemotherapies, and exposure to radiations. Efficient DNA repair mechanisms are essential for the maintenance of genomic integrity, damaged DNA is not replicated and transferred to next generations rather the presence of deleterious DNA initiates signaling cascades leading to the cell cycle arrest or apoptosis. DNA modifications, DNA methylation, histone methylation, histone acetylation, and DNA damage can eventually lead towards apoptosis.

Currently, research on the contribution of genes to the aging process, cellular stability, and longevity of lifespan is at initial stages. The data available is scattered, and the individual reports provide information about the contribution of selected either a gene or a group of similar genes and genetic mechanisms in the regulation of aging and lifespan. Further studies for the identification of potential genetic targets to protect against aging-associated diseases are also required. Finally, the translation of these genetic findings into clinical practice poses a big challenge.

Link: https://doi.org/10.3390/ijms23031499

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