Natural variation of Chronological aging in the Saccharomyces cerevisiae species reveals diet-dependent mechanisms of life span control

Although aging-related mechanisms have widely been investigated through the use of deletion collections isogenic to the reference strain of Saccharomyces cerevisiae (S288c), natural isolates have been poorly exploited to address this research challenge. Here we used a collection of 58 diverse S. cerevisiae strains to explore how natural genetic variation impacts the aging process. Investigation of the chronological life span (CLS) across the collection showed a broad variability of this trait, suggesting the existence of multiple regulatory mechanisms of the aging process governed by genetic diversity. Using both individual and bulk segregant analysis strategies, two major Quantitative Trait Loci (QTLs) were identified within a segregating population obtained by crossing two natural variants with contrasting aging behavior. The detection of those QTLs depended on the nature and concentration of the carbon source present in the medium, confirming the strong interplay between environmental and genetic factors at the basis of life span control. The RIM15 gene, known to be a bottleneck effector of both the Tor- and Ras-related nutrient-sensing pathways, was validated in the first QTL as a major regulator of aging under calorie restricted conditions. More surprisingly, SER1, encoding an aminotransferase involved in the serine synthesis pathway, was identified as a life span control gene in the second QTL, especially under high glucose conditions. Taken together, these results show that genetic linkage studies in crosses of natural yeast isolates represent a promising strategy for uncovering new regulatory mechanisms of chronological aging under different environmental conditions.