Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Autophagy and Longevity

  • Nakamura, Shuhei (Department of Genetics, Graduate School of Medicine, Osaka University) ;
  • Yoshimori, Tamotsu (Department of Genetics, Graduate School of Medicine, Osaka University)
  • Received : 2017.12.05
  • Accepted : 2017.12.29
  • Published : 2018.01.31
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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

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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 thesequestered cargos are degraded and recycled for the maintenance of cellular homeostasis.

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Fig. 2. Autophagy is a convergent mechanism of multiple longevi-ty paradigms. Autophagic activity is commonly elevated in manylong-lived animals and is essential for their longevity, suggestingthat autophagy is one of convergent mechanisms mediatingdifferent longevity paradigms.

Table 1. Longevity through activation of autophagy

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