Genetic circuitry boosts cell longevity

Over the past decade, cellular aging research has been accelerated by the identification of pathways that control the onset of age-associated cell states (the so-called hallmarks of aging) alongside the development of candidate therapeutics that attempt to delay or reverse the onset of aging (1). But what if cells were preprogrammed to undergo cellular aging? Cellular aging in yeast (Saccharomyces cerevisiae) was shown to be controlled by a genetic circuit that forces cells to either slow down heme biosynthesis, leading to mitochondrial dysfunction, or lose their ability to engage in chromatin silencing, leading to ribosomal DNA (rDNA) instability and fragmented nucleoli (2). Simple interventions to this evolutionarily conserved genetic circuit (e.g., overexpressing the key regulators) increased the cell's longevity by modest amounts. On page 376 of this issue, Zhou et al. (3) reveal that introducing designed genetic circuitry to rewire these dynamics increased cellular longevity by 80%.