Jung Paul P, Zhang Zhi, Paczia Nicole, Jaeger Christian, Ignac Tomasz, May Patrick, Linster Carole L
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
NPJ Aging Mech Dis. 2018 Mar 12;4:3. doi: 10.1038/s41514-018-0022-6. eCollection 2018.
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 , 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 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 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.
衰老具有广泛的科学研究价值，尤其是因为它与常见人类疾病有着内在联系。在衰老相关机制方面已经开展了开创性工作，主要是通过使用与S288c参考菌株同基因的缺失文库。在本研究中，我们采用最近发表的高通量方法，在七种不同条件下对58个自然菌株群体中的时序寿命（CLS）进行了量化。我们观察到广泛的衰老变异性，这表明多种遗传和环境因素参与了时序衰老控制。通过将两个具有相反衰老行为的自然分离株杂交获得的双亲群体中，鉴定出了两个主要的数量性状位点（QTL）。这些QTL的检测取决于可供生长的碳源的性质和浓度。在第一个QTL中， 基因被确定为低葡萄糖条件下衰老的主要调节因子，这进一步支持了营养感应途径在热量限制下寿命控制中的重要性。在第二个QTL中，我们发现，编码丝氨酸合成途径中一种保守的转氨酶（此前未发现其与衰老有关）的 基因与CLS调节存在因果关系，特别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，涉及丝氨酸合成与衰老之间的权衡，很可能是通过调节乙酸盐和海藻糖代谢实现的。更普遍地说，它表明跨自然菌株的遗传连锁研究是进一步揭示衰老分子基础的一种有前景的策略。
