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Research Paper

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

Márton L. Tóth, Tímea Sigmond, Éva Borsos, János Barna, Péter Erdélyi, Krisztina Takács-Vellai, László Orosz, Attila L. Kovács, György Csikós, Miklós Sass and Tibor Vellai

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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.

Authors

Márton L. Tóth

ELTE University

Tímea Sigmond

Eötvös Loránd University

Éva Borsos

Eötvös Loránd University

János Barna

Eötvös Loránd University

Péter Erdélyi

Eötvös Loránd University

Krisztina Takács-Vellai

Eötvös Loránd University

László Orosz

Eötvös Loránd University

Attila L. Kovács

Eötvös Loránd University

György Csikós

Eötvös Loránd University

Miklós Sass

Eötvös Loránd University

Tibor Vellai

Eötvös Loránd University

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.