Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling
Autor: | William B. Mair, Kristopher Burkewitz, Heather J. Weir, Renata L.S. Goncalves, Raymond Laboy, Caroline C. Escoubas, Pallas Yao, Matthew D. Hirschey, Frank K. Huynh |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Senescence Aging Physiology media_common.quotation_subject Longevity Biology Mitochondrion AMP-Activated Protein Kinases Mitochondrial Dynamics Article Cell Line 03 medical and health sciences Mice AMP-Activated Protein Kinase Kinases Mitophagy Peroxisomes Metabolomics Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Beta oxidation media_common Caloric Restriction Fatty Acids AMPK Cell Biology Peroxisome Cell biology Mitochondria 030104 developmental biology Biochemistry Models Animal Protein Kinases Homeostasis |
Popis: | 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. |
Databáze: | OpenAIRE |
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