Hanane Hadj-Moussa, Megan Ulusan, Dorottya Horkai, Mohammed Kamran Afzal Mirza, Jonathan Houseley
AssessmentThis study addresses an important question in aging biology by combining metabolomics, transcriptomics, molecular genetics, and functional analyses to examine how cytosolic acetyl-CoA metabolism influences late-life fitness in replicatively aging yeast.The evidence supporting the roles of AMPK activation, mitochondrial acetyl-CoA utilization, and fatty acid synthesis in preserving fitness during aging is convincing overall, and the engineered A2A strain provides an elegant demonstration that coordinated modulation of distinct acetyl-CoA metabolic branches can increase the proportion of aged cells with a low-senescence phenotype.The study provides significant insight into mechanisms that allow aging cells to maintain fitness without extending replicative lifespan.