Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans.
Aging is a multifactorial process with many mechanisms contributing to the decline. Mutations decreasing insulin/IGF-1 (insulin-like growth factor-1) or TOR (target of rapamycin) kinase-mediated signaling, mitochondrial activity and food intake each extend life span in divergent animal phyla. Understanding how these genetically distinct mechanisms interact to control longevity is a fundamental and fascinating problem in biology. Here we show that mutational inactivation of autophagy genes, which are involved in the degradation of aberrant, damaged cytoplasmic constituents accumulating in all aging cells, accelerates the rate at which the tissues age in the nematode Caenorhabditis elegans. According to our results Drosophila flies deficient in autophagy are also short-lived. We further demonstrate that reduced activity of autophagy genes suppresses life span extension in mutant nematodes with inherent dietary restriction, aberrant insulin/IGF-1 or TOR signaling, and lowered mitochondrial respiration. These findings suggest that the autophagy gene cascade functions downstream of and is inhibited by different longevity pathways in C. elegans, therefore, their effects converge on autophagy genes to slow down aging and lengthen life span. Thus, autophagy may act as a central regulatory mechanism of animal aging.
Tóth
Márton L
ML
Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
Sigmond
Tímea
T
Borsos
Eva
E
Barna
János
J
Erdélyi
Péter
P
Takács-Vellai
Krisztina
K
Orosz
László
L
Kovács
Attila L
AL
Csikós
György
G
Sass
Miklós
M
Vellai
Tibor
T
D000375:Aging / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000235:genetics; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008136:Longevity / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D017853:Phosphotransferases (Alcohol Group Acceptor); C472494:let-363 protein, C elegans