Aging is a complex trait of broad scientific interest, especially because of its intrinsic link with common human diseases. Pioneering work on aging-related mechanisms has been made in Saccharomyces cerevisiae, mainly through the use of deletion collections isogenic to the S288c reference strain. In this study, using a recently published high-throughput approach, we quantified chronological life span (CLS) within a collection of 58 natural strains across seven different conditions. We observed a broad aging variability suggesting the implication of diverse genetic and environmental factors in chronological aging control. Two major Quantitative Trait Loci (QTLs) were identified within a biparental population obtained by crossing two natural isolates with contrasting aging behavior. Detection of these QTLs was dependent upon the nature and concentration of the carbon sources available for growth. In the first QTL, the RIM15 gene was identified as major regulator of aging under low glucose condition, lending further support to the importance of nutrient-sensing pathways in longevity control under calorie restriction. In the second QTL, we could show that the SER1 gene, encoding a conserved aminotransferase of the serine synthesis pathway not previously linked to aging, is causally associated with CLS regulation, especially under high glucose condition. These findings hint toward a new mechanism of life span control involving a trade-off between serine synthesis and aging, most likely through modulation of acetate and trehalose metabolism. More generally it shows that genetic linkage studies across natural strains represent a promising strategy to further unravel the molecular basis of aging.

衰老是一项具有广泛科学兴趣的复杂特征，尤其是由于其与人类常见疾病的内在联系。在酿酒酵母中已经进行了与衰老相关的机制的开拓性工作。，主要是通过使用与S288c参考菌株同基因的缺失集合来实现的。在这项研究中，我们使用了最近发布的高通量方法，对在七个不同条件下的58种自然菌株的集合中的时间序列寿命（CLS）进行了量化。我们观察到广泛的衰老变异性，表明在时序衰老控制中涉及多种遗传和环境因素。在双亲群体中鉴定出两个主要的数量性状基因座（QTL），该双亲群体是通过使两个自然分离株具有相反的衰老行为而获得的。这些QTL的检测取决于可用于生长的碳源的性质和浓度。在第一个QTL中，RIM15该基因被认为是低葡萄糖条件下衰老的主要调节剂，这进一步支持了养分感应途径在卡路里限制下长寿控制中的重要性。在第二个QTL中，我们可以证明，SER1基因编码的丝氨酸合成途径的保守氨基转移酶以前没有与衰老相关，与CLS调节有因果关系，尤其是在高葡萄糖条件下。这些发现暗示了一种新的寿命控制机制，该机制涉及丝氨酸合成与衰老之间的权衡，这很可能是通过调节乙酸盐和海藻糖的代谢来实现的。更一般地说，它表明跨自然菌株的遗传连锁研究代表了一种进一步揭示衰老的分子基础的有前途的策略。