Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans

ML Tóth, T Sigmond, É Borsos, J Barna, P Erdélyi… - Autophagy, 2008 - Taylor & Francis
ML Tóth, T Sigmond, É Borsos, J Barna, P Erdélyi, K Takács-Vellai, L Orosz, AL Kovács
Autophagy, 2008Taylor & Francis
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 …
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.
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