The Key to Healthy Longevity
German researchers from the Institute for the Study of Aging – the Fritz Lipmann Institute in Jena, working under the leadership of Dr. Karl Lenhard Rudolph, identified the Per2 gene, the deletion of which stabilizes the number of immune cells in the blood of aging mice and increases their life expectancy by increasing the effectiveness of immune protection.
Aging of the body is accompanied by an increased risk of developing chronic and acute infectious diseases. The reason for this is a decrease in the ability of hematopoietic stem cells (HSCs) to give rise to a sufficient number of immune cells. The process of their differentiation into lymphocytes is particularly affected, which leads to a change in the quantitative ratio of blood cells and the appearance of immune defense disorders that worsen the overall health of an aging organism. There are experimental data according to which the accumulation of DNA damage contributes to the occurrence of such immune disorders.
As part of their latest study, the authors conducted a screening of 459 genes in experiments on mice using the RNA interference method, presumably having suppressive properties against tumors. The purpose of this was to identify genes that limit the potential of hematopoietic stem cells to self-renew in response to DNA damage and aging. According to the screening results, the most important factor limiting the viability and repopulation potential of hematopoietic stem cells was the Per2 gene, previously known as one of the genes regulating the sleep-wake cycle.
Researchers have demonstrated that deletion of this gene increases the efficiency of hematopoietic stem cells' response to DNA damage, which leads to stabilization of their functioning in the body of aging mice, preservation of normal lymphocyte production and, accordingly, improvement of immune function. It is also important that the described effect extended to DNA damage caused by shortening of the protective end sections of telomere chromosomes – a mechanism considered one of the main components of the human aging process.
Observations of such animals demonstrated their lower susceptibility to infectious diseases, which increased life expectancy by 15% without increasing the incidence of cancer.
Graph from an article in Nature Cell Biology.
According to the authors, the results obtained are both very promising and unexpected, since the existence of such a pronounced relationship between the neutralization of one gene and the work of the immune system turned out to be quite unexpected. In the future, it is necessary to find out whether it applies to humans. Despite the fact that there is a fairly pronounced genetic similarity between humans and mice, genes usually regulate many processes in the body, and the potential side effects of deletion of the Per2 gene need to be carefully clarified. An interesting fact is that mutations of this gene in humans are associated with severe sleep disorders, leading to severe fatigue of patients in the early evening hours. To date, it is unclear whether such mutations have positive effects, such as improving immune function in old age. This is a question researchers have yet to figure out.
Article by Wang J et al. Per2 induction limits lymphoid-biased haematopoietic stem cells and lymphopoiesis in the context of DNA damage and aging is published in the journal Nature Cell Biology.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Leibniz Institute on Aging – Fritz Lipmann Institute: Turn off Per2 – Turn on Healthy Aging
21.04.2016