Researchers at The Wistar Institute have defined a key target of an evolutionarily conserved protein that regulates the process of aging. The study, published June 11 in Nature, provides fundamental knowledge about key mechanisms of aging that could point toward new anti-aging strategies and cancer therapies.

Scientists have long known that a class of proteins called sirtuins promotes fitness and longevity in most organisms ranging from single-celled yeast to mammals. 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. The team, led by senior author Shelley Berger, Ph.D., Hilary Koprowski Professor at The Wistar Institute, 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.

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02 Research Team Finds Key Target Of Aging Regulator

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