Life Span Extension and H2O2 Resistance Elicited by Caloric Restriction Require the Peroxiredoxin Tsa1 in Saccharomyces cerevisiae

SummaryCaloric restriction (CR) extends the life span of organisms ranging from yeast to primates. Here, we show that the thiol-dependent peroxiredoxin Tsa1 and its partner sulfiredoxin, Srx1, are required for CR to extend the replicative life span of yeast cells. Tsa1 becomes hyperoxidized/inactive during aging, and CR mitigates such oxidation by elevating the levels of Srx1, which is required to reduce/reactivate hyperoxidized Tsa1. CR, by lowering cAMP-PKA activity, enhances Gcn2-dependent SRX1 translation, resulting in increased resistance to H2O2 and life span extension. Moreover, an extra copy of the SRX1 gene is sufficient to extend the life span of cells grown in high glucose concentrations by 20% in a Tsa1-dependent and Sir2-independent manner. The data demonstrate that Tsa1 is required to ensure yeast longevity and that CR extends yeast life span, in part, by counteracting age-induced hyperoxidation of this peroxiredoxin.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (121 K)Download as PowerPoint slideHighlights► The peroxiredoxin Tsa1 is required for CR to extend yeast replicative life span ► CR counteracts age-induced hyperoxidation of Tsa1 by elevating Srx1 levels ► CR, by decreasing cAMP-PKA activity, increases translation of the SRX1 mRNA ► An extra copy of the SRX1 gene retards yeast aging at high levels of glucose