Longevity and epigenetics
Natural selection has produced mammals that age at different rates. You can compare, for example, naked diggers and mice: the former can live up to 41 years, almost ten times longer than rodents of a similar size, such as mice.
What explains the longer life span? According to new research by biologists from University of Rochester, the answer lies in the mechanisms that regulate gene expression.
Professor Vera Gorbunova, Professor Andrey Seluanov and graduate student Jinlong Lu studied the genes associated with life expectancy and identified the specific characteristics of these genes. They showed that two regulatory systems controlling gene expression — circadian and pluripotent networks — are crucial for longevity. The results obtained not only reveal the secret of longevity, but also provide new targets for combating aging and age-related diseases.
Comparison of longevity genes
The researchers compared the gene expression of 26 mammalian species with different lifespans – from two years (shrews) to 41 years (naked diggers). They identified thousands of genes associated with the species' maximum lifespan, which either positively or negatively correlated with longevity.
The researchers found that long-lived species tend to have low expression of genes involved in energy metabolism and inflammation, and high expression of genes involved in DNA repair, RNA transport and cytoskeleton organization. Previous studies by Gorbunova and Seluanov have shown that features such as more effective DNA repair and a weaker inflammatory response are characteristic of mammals with a long lifespan.
The opposite was true for short-lived species, which, as a rule, had high expression of genes involved in energy metabolism and inflammation, and low expression of genes involved in DNA repair, RNA transport and cytoskeleton organization.
Two pillars of longevity
The researchers analyzed the mechanisms regulating the expression of these genes and found two main systems. Genes that negatively affect life expectancy (regulate energy metabolism and inflammation) are controlled by circadian networks. In other words, their expression depends on the time of day, which means that it is potentially possible to exercise at least some control over "negative" genes by observing sleep and wakefulness.
On the other hand, the "positive" longevity genes that are involved in DNA repair, RNA transport and cytoskeleton organization are controlled by the so-called pluripotency network. This network participates in the reprogramming of somatic cells into embryonic cells, repacking DNA, which disorganizes with age.
Thus, the pluripotency network and its association with positive longevity genes is an important discovery for understanding how longevity develops.
This study provides a number of possible anti-aging interventions that will increase the expression of positive genes and reduce the expression of negative genes.
Article by J. Yuyang Lu et al. Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation published in the journal Cell Metabolism.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Rochester: The secret to a longer lifespan? Gene regulation holds a clue.