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Autophagy and Ageing

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Ageing: Lessons from C. elegans

Part of the book series: Healthy Ageing and Longevity ((HAL))

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Abstract

Autophagy is a conserved cellular recycling process that plays critical roles in development, disease, and ageing. During autophagy, cytosolic components are sequestered in double-membrane vesicles that ultimately fuse with lysosomes, where the cargo is degraded and recycled. Intriguingly, genetic and pharmacological experiments in C. elegans have shown that all of the longevity paradigms analysed to date, ranging from reduced insulin/IGF-1 signalling to spermidine supplementation, require autophagy genes for lifespan extension. Moreover, many of the long-lived animals show changes in steady-state levels of autophagy markers and/or display increased transcription of autophagy-related and lysosomal genes via conserved transcription factors such as HLH-30/TFEB. These observations are consistent with the notion that increased autophagy is critical for lifespan extension in C. elegans. Similar genetic links have been reported in other organisms, including flies and mice, where overexpression of certain autophagy-related genes is sufficient to extend lifespan. Although clearance of lipids (lipophagy) and mitochondria (mitophagy) have been proposed as selective types of autophagy with relevance to C. elegans ageing, it is still unclear how long-lived animals may induce autophagy to improve their overall healthspan, or how autophagy is regulated in different tissues during normal ageing. Understanding these mechanisms will be critical for targeting autophagy in higher organisms. This chapter summarizes our current knowledge of the links between autophagy and ageing in C. elegans.

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Notes

  1. 1.

    Nomenclature: Yeast genes/proteins are stated first, followed by the mammalian and C. elegans names, if different.

  2. 2.

    Paradoxically, one report has suggested that adult-only RNAi inhibition of several autophagy genes can result in lifespan extension in C. elegans [32]; however, this study was performed on a very small number of animals in the presence of 5-fluoro-2′deoxyuridine, and results were not analysed by survival statistics.

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Acknowledgments

I wish to acknowledge Hansen lab members and Dr. Anne O’Rourke for feedback on the manuscript, and Dr. Caroline Kumsta for help with Table 15.2. MH was supported by NIH/NIA (R01 AG038664 and R01 AG039756) and a Julie Martin Mid-Career Award in Aging Research supported by The Ellison Medical Foundation and AFAR.

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  1. Program for Development, Aging and Regeneration, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, USA

    Malene Hansen

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Correspondence to Malene Hansen .

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  1. Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

    Anders Olsen

  2. Department of Metabolics & Aging, The Scripps Research Institute - Scripps Florida, Jupiter, Florida, USA

    Matthew S. Gill

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Hansen, M. (2017). Autophagy and Ageing. In: Olsen, A., Gill, M. (eds) Ageing: Lessons from C. elegans. Healthy Ageing and Longevity. Springer, Cham. https://doi.org/10.1007/978-3-319-44703-2_15

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