Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae

Yeast metacaspase: Grim Reaper or savior? Yeast metacaspases are structural and possibly functional homologs of caspases that execute apoptosis—programmed cell death—in higher organisms. Malmgren Hill et al. tested whether yeast metacaspase Mca1 acts as an executioner or beneficial protein during replicative aging of yeast (see the Perspective by Kampinga). Boosting metacaspase levels caused a substantial and robust extension of life span. This lifespan extension was only partly dependent on the caspase activity of Mca1 but required the presence of the protein disaggregase Hsp104. Consistent with a role in proteostasis, Mca1 was recruited to chaperone-enriched aggregates during aging. Mca1 increased aggregate asymmetry during yeast cytokinesis and counteracted the age-associated accumulation of inclusions. Science , this issue p. 1389 ; see also p. 1341