To get to the origins of genetics/epigenetics of aging and longevity

Since the dawn of civilization, people continue to search for the secrets of longevity and try to prolong their lives. However, only over the past two decades, thanks to advances in genome sequencing and epigenetic analysis, as well as increased government funding for this industry, there has been a rapid accumulation of new data that has allowed researchers to develop comprehensive models and theories of aging. While experts have not yet come to a consensus, evolutionary theories continue to dominate in this area. These theories predict the existence of certain genes that provide an advantage in natural selection at the early stages of life and at the same time negatively affect life expectancy, that is, genes that ensure survival.

On the other hand, researchers are discovering more and more new human and animal genes, mutations or overexpression of which lead to an increase in life expectancy – the so-called gerontogens. Moreover, it reveals genetic and epigenetic mechanisms that have a positive effect on longevity.

Researchers from Russia and the USA conducted a comprehensive analysis of the scientific data collected to date and found that most of the genes involved in the regulation of life expectancy, as well as genetic and epigenetic mechanisms, are closely interrelated with the mechanisms of stress reaction development. This confirms the existence of the so-called "longevity program".

As a rule, the regulatory genes of the longevity program suppress moderate stress reactions. Moderate overexpression of longevity effector genes involved in the development of stress reactions to damage to DNA, proteins or other cellular components increases life expectancy. Whereas moderate stress induces a "longevity program" by stimulating the expression of survival genes, which ensures the prevention or elimination of damage, chronic or acute stress reactions deplete the defense mechanisms and accelerate aging.

Processes regulated by genes that accelerate and slow down aging exist at all levels of the body, from molecular to organ systems. Their multilevel organization, the interpenetration of levels, as well as the interaction of regular and stochastic elements form the aging process.

According to one of the authors of the study, Professor Alexey Moskalev from the Institute of Biology of the Russian Academy of Sciences, the study of the effect of mutations and epimutations on life expectancy and the rate of aging expands the range of potential pharmacological and gene therapy targets, as well as biomarkers that can be used in the treatment of age-related diseases.

The researchers also analyzed in detail for the first time the state grants issued for the study of genes involved in the aging process. According to the authors, one of the tools that can help to understand the direction of the development of unpublished scientific research is the analysis of resumes in grant applications.

Based on the results of such an analysis, they came to interesting conclusions. The research area of aging genetics is relatively young. The p53 gene was identified in 1979, and its role in aging was established in 1987. On average, the aging genes known today were identified 21 years ago, while an average of 9.7 years passed before their first mention together with the term "aging". The approximate amount of funding spent on the study of aging-associated genes amounted to more than $8.5 billion, which resulted in more than 195,000 publications. At the same time, most of the funding was spent on studying the genes involved in the stress response.

The largest amount spent on the study of one gene, subject to the presence of the term "aging" in the resume submitted for the grant, amounted to 195 million US dollars, which corresponds to less than 5% of the total funding spent on the study of the p53 gene. SIRT1 is the only gene that has spent more than 100 million on the analysis of its role in aging. At the same time, only 14% of the funding was spent on studying its properties that are not related to the aging process. Most of the genes associated with aging and longevity are involved in other biological processes, so most of the funding and publications in which they are mentioned relate to other areas of research.

Article by Alexey A Moskalyov et al. Genetics and epigenetics of aging and longevity is published in the journal Cell Cycle.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
Drilling into trends in genetics, epigenetics of aging, longevity.

01.04.2014