Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.

Published

Journal Article

Mitochondrial network remodeling between fused and fragmented states facilitates mitophagy, interaction with other organelles, and metabolic flexibility. Aging is associated with a loss of mitochondrial network homeostasis, but cellular processes causally linking these changes to organismal senescence remain unclear. Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity in C. elegans via maintaining mitochondrial network homeostasis and functional coordination with peroxisomes to increase fatty acid oxidation (FAO). Inhibiting fusion or fission specifically blocks AMPK- and DR-mediated longevity. Strikingly, however, preserving mitochondrial network homeostasis during aging by co-inhibition of fusion and fission is sufficient itself to increase lifespan, while dynamic network remodeling is required for intermittent fasting-mediated longevity. Finally, we show that increasing lifespan via maintaining mitochondrial network homeostasis requires FAO and peroxisomal function. Together, these data demonstrate that mechanisms that promote mitochondrial homeostasis and plasticity can be targeted to promote healthy aging.

Full Text

Duke Authors

Cited Authors

  • Weir, HJ; Yao, P; Huynh, FK; Escoubas, CC; Goncalves, RL; Burkewitz, K; Laboy, R; Hirschey, MD; Mair, WB

Published Date

  • December 2017

Published In

Volume / Issue

  • 26 / 6

Start / End Page

  • 884 - 896.e5

PubMed ID

  • 29107506

Pubmed Central ID

  • 29107506

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2017.09.024

Language

  • eng