Graphic: Courtesy of Shin-Ichiro Imai
 SILENCE OF THE CHROMATIN: The Sir2 protein requires NAD for its enzymatic activity. It couples NAD breakdown to nicotinamide and ADP-ribose with the removal of acetyl groups from histone and other proteins. The acetyl moiety is transferred to ADP-ribose, which creates the chemical acetyl-ADP ribose. Deacetylated nucleosome are packed up to silenced chromatin structure and involved in silencing gene transcription. This Sir2 enzymatic activity links energy metabolism, chromatin silencing, and aging.

Some twenty years ago, Massachusetts Institute of Technology biologist Lenny Guarente began studying aging by timing the lifespan of various yeast strains. Finding one mutant strain that lived about 50% longer than the others, Guarente's team searched the mutant's genome to uncover its secret to long life. The investigation singled out a silent information regulator gene called Sir2, which was expressed at a higher-than-normal rate.

Learning just how Sir2 functions to extend life...

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