RRC ID 51508
Author Weir HJ, Yao P, Huynh FK, Escoubas CC, Goncalves RL, Burkewitz K, Laboy R, Hirschey MD, Mair WB.
Title Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.
Journal Cell Metab
Abstract 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.
Volume 26(6)
Pages 884-896.e5
Published 2017-12-5
DOI 10.1016/j.cmet.2017.09.024
PII S1550-4131(17)30612-5
PMID 29107506
PMC PMC5718936
MeSH AMP-Activated Protein Kinase Kinases Aging Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Caloric Restriction* Cell Line Fatty Acids / metabolism Longevity* Metabolomics Mice Mitochondria / metabolism* Mitochondria / ultrastructure Mitochondrial Dynamics Models, Animal Peroxisomes / metabolism* Protein Kinases / metabolism*
IF 21.567
Times Cited 79
C.elegans tm1107 tm1108 tm1133