17 June 2009

The key target of the aging regulator has been discovered

Wistar Institute team finds key target of aging regulatorEurekAlert!, translation: Gerovital.Ru

Scientists from the Wistar Institute have identified a key target of an evolutionarily conservative protein that regulates the aging process. The study, published on June 11 in the journal Nature (Histone H4 lysine 16 acetylation regulates cellular lifespan), provides fundamental knowledge about the key mechanisms of aging that can indicate new strategies for rejuvenation and anti-cancer therapy.

Scientists have long known that a class of proteins called sirtuins maintains good physical condition and longevity in most organisms, starting with unicellular yeast and including mammals. Sirtuins at the cellular level maintain the integrity of the genome, increase resistance to adverse factors and resist physiological aging. Nevertheless, the underlying molecular mechanisms of this phenomenon remain insufficiently studied. A team of scientists led by Prof. Shelley Berger and Prof. Hilary Koprowski from the Wistar Institute for the first time demonstrated the molecular target of one of the representatives of this class of proteins, Sir2, in the process of regulating the aging of yeast cells. The Sir2 protein cleaves off the acetyl group associated with a specific site (lysine at position 16 or K16) of the histone H4 molecule; histones are proteins that pack and organize long DNA strands in the nucleus, and are also the main regulators of switching genes on and off. This study shows that the cleavage of acetyl groups by the Sir2 protein near the end sites of chromosomes – telomeres – is important for maintaining the ability to cell division in yeast. Scientists have found that in the process of cell aging, the level of Sir2 decreases and at the same time acetyl tags accumulate, accompanied by a violation of the organization of histones of telomeres.

Deacetylation of H4K16 by Sir2 and subsequent stabilization of telomeres play a major role in maintaining a long lifespan in yeast. Since sirtuins deacetylate many different proteins, the results obtained clarify the key role of the Sir2 protein in controlling life expectancy.

"Some changes in histone molecules, such as acetylation of lysine 16 on histone H4, are stable and persist through generations of cell divisions. This kind of inheritance, independent of DNA, is called epigenetic," says Berger. – "In recent years, characteristic epigenetic features have been discovered for various developmental processes. Understanding the epigenetic changes associated with aging processes is the most fascinating area among all the studies of aging. This gives an understanding of the essence of the physiological aging process and new ideas and methods for regulating cells that have lost control over proliferation, such as "immortal" cancer cells, as well as new strategies for maintaining health and good physical shape."

"We plan to continue research in the search for new targets of Sir2 and other regulators of aging," says the lead author, Prof. Weiwei Dan (Weiwei Dang), a researcher from the Berger team. "We are developing objective research methods for the remaining aging targets and the mechanisms of their interaction with chromatin. The use of yeast in this aging model makes it possible to conduct studies that are impossible on other, more complex organisms. It is significant that many of these chromatin mechanisms in yeast are also applicable to the aging of human cells."

Portal "Eternal youth" http://vechnayamolodost.ru/16.06.2009

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