The Wistar Institute researchers have defined a key target of an evolutionarily conserved protein that can help turn back the age clock.
The study, which has been published in Nature, provides fundamental knowledge about key mechanisms of aging.It has been long known that a class of proteins called sirtuins promotes fitness and longevity in most organisms. At the cellular level, sirtuins protect genome integrity, enhance resistance to adverse stresses, and antagonize senescence.
However, the underlying molecular mechanisms have remained poorly understood.
Now, in the latest study, senior author Shelley Berger, Ph.D., Hilary Koprowski Professor at The Wistar Institute, has demonstrated for the first time a molecular target for a member of this class, Sir2, in regulation of aging in yeast cells.
Sir2 removes an acetyl group attached to a specific site (lysine at position 16 or K16) on histone H4-histones are proteins that package and organize the long strands of DNA within the nucleus and also are central regulators in turning genes on and off. The study reveals that removal of this acetyl group by Sir2 near the chromosome ends-the telomeres-is important for yeast cells to maintain the ability to replicate. Researchers found that Sir2 levels decline as cells age, and there is a concomitant accumulation of the acetylation mark along with disrupted histone organization at telomeres.
Deacetylation of H4K16 by Sir2 and consequent telomere stability play a major role in maintaining long lifespan in yeast. Since sirtuins deacetylate many different proteins, these results clarify a key role of Sir2 protein in control of lifespan.
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"Characteristic epigenetic features have been discovered for various developmental processes in recent years. Understanding epigenetic changes associated with aging is a hugely exciting direction in aging research. It will provide insights and ideas not only for new therapies to regulate cells that have lost control of proliferation, such as 'immortal' cells found in cancers, but also for new strategies to maintain health and fitness."
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Source-ANI
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