Independent regulation of age associated fat accumulation and longevity
Anthony O. Beas, Patricia B. Gordon, Clara L. Prentiss, Carissa Perez Olsen, Matthew A. Kukurugya, Bryson D. Bennett, Susan M. Parkhurst, Daniel E. Gottschling
Abstract
Abstract Age-dependent changes in metabolism can manifest as cellular lipid accumulation, but how this accumulation is regulated or impacts longevity is poorly understood. We find that Saccharomyces cerevisiae accumulate lipid droplets (LDs) during aging. We also find that over-expressing BNA 2 , the first Biosynthesis of NAD + (kynurenine) pathway gene, reduces LD accumulation during aging and extends lifespan. Mechanistically, this LD accumulation during aging is not linked to NAD + levels, but is anti-correlated with metabolites of the s hikimate and a romatic amino acid biosynthesis (SA) pathways (upstream of BNA2 ), which produce tryptophan (the Bna2p substrate). We provide evidence that over-expressed BNA2 skews glycolytic flux from LDs towards the SA-BNA pathways, effectively reducing LDs. Importantly, we find that accumulation of LDs does not shorten lifespan, but does protect aged cells against stress. Our findings reveal how lipid accumulation impacts longevity, and how aging cell metabolism can be rewired to modulate lipid accumulation independently from longevity.