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Genes Dev. 2017 Aug 1;31(15):1561-1572. doi: 10.1101/gad.301648.117. Epub 2017 Sep 7.

Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans.

Author information

1
Laboratory of Molecular Epigenetics, Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
2
Faculty of Biology, Johannes Gutenberg University, 55099 Mainz, Germany.
3
Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center (MDC), 13125 Berlin, Germany.

Abstract

Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including pha-4 Through downstream analysis of pha-4, we identified that the inactivation of genes governing the early stages of autophagy up until the stage of vesicle nucleation, such as bec-1, strongly extend both life span and health span. Furthermore, our data demonstrate that the improvements in health and longevity are mediated through the neurons, resulting in reduced neurodegeneration and sarcopenia. We propose that autophagy switches from advantageous to harmful in the context of an age-associated dysfunction.

KEYWORDS:

BEC-1; C. elegans; aging; antagonistic pleiotropy; autophagy; neurodegeneration

PMID:
28882853
PMCID:
PMC5630021
DOI:
10.1101/gad.301648.117
[Indexed for MEDLINE]
Free PMC Article

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