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

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 pleiotrop...

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Bibliographic Details
Published in:Genes & development 2017-08, Vol.31 (15), p.1561-1572
Main Authors: Wilhelm, Thomas, Byrne, Jonathan, Medina, Rebeca, Kolundžić, Ena, Geisinger, Johannes, Hajduskova, Martina, Tursun, Baris, Richly, Holger
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Autophagy - physiology
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Cytoplasm - metabolism
Gene Silencing - physiology
Genetic Pleiotropy
Longevity
Neurons - metabolism
Reproduction
Research Paper
RNA Interference - physiology
Signal Transduction
Trans-Activators - genetics
Trans-Activators - metabolism
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
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Summary: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 Through downstream analysis of , we identified that the inactivation of genes governing the early stages of autophagy up until the stage of vesicle nucleation, such as , 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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.301648.117