The mammalian longevity associated acetylome

In recent decades, human longevity has reached unprecedented levels; life expectancy continues to rise, and this trend is expected to persist. However, this rise is accompanied by a higher incidence of aging-related diseases, including inflammation, neurodegeneration, and cancer. As a result, developing strategies to extend healthspan alongside lifespan has become increasingly important.

To address this challenge, a new article in Nature Communications by Prof. Haim Cohen and colleagues draws on the most powerful and enduring experiment ever conducted: evolution. The researchers developed PHARAOH (Post-translational modificAtions Regulator Of Healthspan), a tool designed to compare protein sequences across 107 mammalian species with diverse lifespans. By focusing on post-translational modifications, particularly acetylation, PHARAOH identifies evolutionary amino acid substitutions distinguishing short- and long-lived mammals. These longevity-associated acetylations were experimentally validated by modifying proteins involved in healthspan-enhancing pathways. This study presents a novel strategy for identifying therapeutic targets aimed at extending both healthspan and lifespan.