A novel gene-diet pair modulates C. elegans aging

Diet profoundly affects metabolism and incidences of age-related diseases. Animals adapt their physiology to different food-types, modulating complex life-history traits like aging. The molecular mechanisms linking adaptive capacity to diet with aging are less known. We identify FLR-4 kinase as a novel modulator of aging in C. elegans, depending on bacterial diet. FLR-4 functions to prevent differential activation of the p38MAPK pathway in response to diverse food-types, thereby maintaining normal life span. In a kinase-dead flr-4 mutant, E. coli HT115 (K12 strain), but not the standard diet OP50 (B strain), is able to activate p38MAPK, elevate expression of cytoprotective genes through the nuclear hormone receptor NHR-8 and enhance life span. Interestingly, flr-4 and dietary restriction utilize similar pathways for longevity assurance, suggesting cross-talks between cellular modules that respond to diet quality and quantity. Together, our study discovers a new C. elegans gene-diet pair that controls the plasticity of aging.饮食可显著影响机体代谢与年龄相关性疾病的发病率。动物可通过调整自身生理状态以适应不同食物类型，进而调控衰老等复杂的生活史性状。目前，将饮食适应性与衰老相关联的分子机制仍未明确。本研究鉴定出FLR-4激酶（FLR-4 kinase）是秀丽隐杆线虫（C. elegans）中一类依赖细菌饮食的新型衰老调控因子。FLR-4的功能是防止机体在响应不同食物类型时出现p38丝裂原活化蛋白激酶（p38MAPK）通路的差异化激活，从而维持正常寿命。在激酶失活的flr-4突变体中，大肠杆菌（E. coli）HT115（K12菌株）而非标准饮食OP50（B菌株）可激活p38MAPK通路，通过核激素受体NHR-8（nuclear hormone receptor NHR-8）上调细胞保护性基因的表达，并延长寿命。值得注意的是，flr-4与膳食限制通过相似的通路实现寿命保障，这提示响应食物质量与数量的细胞模块之间存在交叉对话。综上，本研究发现了一对可调控衰老可塑性的全新秀丽隐杆线虫基因-饮食组合。