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

• 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
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.301648.117

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.