A connection between two aging pathways has been found

Link Between Two Aging Pathways In Mice Uncovered (ScienceDaily)
Translation: Gerovital.RuThe cancellation or suspension of such a molecular "betrayal" (although this is a matter of the distant future) will allow us, if not to prevent, then at least to postpone the appearance of the next wrinkle.

"There is a certain genetic process that determines the course of aging of the body," says Howard Chang, MD, associate professor of dermatology and an employee of the Stanford Cancer Center (Stanford's Cancer Center). "It is possible that rare centenarians living for more than 100 years have a less effective version of this process, while children suffering from progeria – a genetic disease of accelerated aging – have more active components of it."

The study, the results of which were published on January 9 in Cell, is based on a three-year collaboration between Chang and Katrin Chua, MD, associate professor of Endocrinology, Gerontology and Metabolism at Stanford and an employee of the Stanford Cancer Center on the one hand and the Veterans Affairs Palo Alto Health Care System) – on the other hand. Chang and Chua are the leaders of the study.

Scientists have focused their attention on two seemingly different ways of aging. One of them is associated with the SIRT6 molecule, a member of the sirtuin family of proteins responsible for the lifespan of organisms such as yeast and worms, the study of which continued in Chua's laboratory for several years. She and her colleagues have previously demonstrated that SIRT6 is involved in genomic stability and protection of the ends of chromosomes called telomeres. Telomeres, which become shorter and shorter with each cell division, act like an internal molecular clock associated with the aging process. In addition, mice that do not have SIRT6 are born, but, as a rule, within a few weeks, due to the rapid, resembling premature aging, degeneration of all organs, die.

"Representatives of the sirtuin family are involved in the aging of the body and the occurrence of age-related diseases," says Chua, "but until recently very little was known about how SIRT6 works at the molecular level. Our study showed that SIRT6, in addition to being involved in genomic stability and telomere protection, also regulates gene expression."

Another pathway is associated with the more well-known protein NF-kB, which attaches to and controls the expression of many genes, including genes involved in aging. The expression of many of these genes increases with age. Blocking the activity of NF-kB in the skin cells of old mice makes them look and function like young cells.

Scientists have become interested in whether NF-kB and SIRT6 interact, "helping" cells to age properly? They found that in humans and mice, SIRT6 combines with the NF-kB derivative and modifies compounds located near the center of the DNA chain (histones). Due to such changes in NF-kV, it becomes more difficult to stimulate the expression of aging genes.

"It seems that the task of SIRT6 is to restrain NF-kB and limit the expression of genes associated with the aging process," explains Chang. "For several years we have been studying the influence of regulatory genes, such as NF-kV, on the aging process of the body. And so we were lucky enough to discover a biochemical relationship between these two pathways."

Young mice without the SIRT6 protein had elevated levels of NF-kB-dependent genes involved in the immune response, signal transmission in the cell and metabolism. Potentially, all these genes are involved in a deadly, aging-like disease that killed such mice within four weeks after birth. Suppression of gene expression for the NF-kB-SIRT binding element allowed some mice to avoid this fate.

"Mice without SIRT6, at the age of about four weeks, seemed to encounter some kind of obstacle when their sugar levels dropped to a barely compatible with life level," says Chua. "A decrease in the activity of NF-kV allowed mice to cope with this condition and live longer. Using the example of these mice, we can study the consequences of a lack of SIRT6 in older individuals."

Currently, scientists are trying to understand how the NF-kV "learns" when and to what extent to initiate the degenerative process, and what role SIRT6 plays in this.

"This is a very provocative question," says Chang. "We have combined previously separate pathways involved in aging into one. Now we would like to know what controls it."

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06.02.2009