Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 41 (1), 65-72

Autophagy and Longevity

Affiliations
Review

Autophagy and Longevity

Shuhei Nakamura et al. Mol Cells.

Abstract

Autophagy is an evolutionally conserved cytoplasmic degradation system in which varieties of materials are sequestered by a double membrane structure, autophagosome, and delivered to the lysosomes for the degradation. Due to the wide varieties of targets, autophagic activity is essential for cellular homeostasis. Recent genetic evidence indicates that autophagy has a crucial role in the regulation of animal lifespan. Basal level of autophagic activity is elevated in many longevity paradigms and the activity is required for lifespan extension. In most cases, genes involved in autophagy and lysosomal function are induced by several transcription factors including HLH-30/TFEB, PHA-4/FOXA and MML-1/Mondo in long-lived animals. Pharmacological treatments have been shown to extend lifespan through activation of autophagy, indicating autophagy could be a potential and promising target to modulate animal lifespan. Here we summarize recent progress regarding the role of autophagy in lifespan regulation.

Keywords: C. elegans; aging; autophagy; longevity; transcription factors.

Figures

Fig. 1
Fig. 1. Overview of macroautophagy
Upon induction of autophagy by stress, cytoplasmic materials are sequestered by a double-membraned structure, called an autophagosome. These autophagosomes fuse with lysosomes to become autolysosomes, in which the sequestered cargos are degraded and recycled for the maintenance of cellular homeostasis.
Fig. 2
Fig. 2. Autophagy is a convergent mechanism of multiple longevity paradigms
Autophagic activity is commonly elevated in many long-lived animals and is essential for their longevity, suggesting that autophagy is one of convergent mechanisms mediating different longevity paradigms.

Similar articles

See all similar articles

Cited by 21 PubMed Central articles

See all "Cited by" articles

References

    1. Alvers AL, Fishwick LK, Wood MS, Hu D, Chung HS, Dunn WA, Jr, Aris JP. Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae. Aging Cell. 2009a;8:353–369. - PMC - PubMed
    1. Alvers AL, Wood MS, Hu D, Kaywell AC, Dunn WA, Jr, Aris JP. Autophagy is required for extension of yeast chronological life span by rapamycin. Autophagy. 2009b;5:847–849. - PMC - PubMed
    1. Apfeld J, O’Connor G, McDonagh T, DiStefano PS, Curtis R. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev. 2004;18:3004–3009. - PMC - PubMed
    1. Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11:35–46. - PMC - PubMed
    1. Chan SN, Tang BL. Location and membrane sources for autophagosome formation - from ER-mitochondria contact sites to Golgi-endosome-derived carriers. Mol Membr Biol. 2013;30:394–402. - PubMed

LinkOut - more resources

Feedback