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

Publication ,  Journal Article
Weir, HJ; Yao, P; Huynh, FK; Escoubas, CC; Goncalves, RL; Burkewitz, K; Laboy, R; Hirschey, MD; Mair, WB
Published in: Cell Metab
December 5, 2017

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.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

December 5, 2017

Volume

26

Issue

6

Start / End Page

884 / 896.e5

Location

United States

Related Subject Headings

  • Protein Kinases
  • Peroxisomes
  • Models, Animal
  • Mitochondrial Dynamics
  • Mitochondria
  • Mice
  • Metabolomics
  • Longevity
  • Fatty Acids
  • Endocrinology & Metabolism
 

Citation

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Weir, H. J., Yao, P., Huynh, F. K., Escoubas, C. C., Goncalves, R. L., Burkewitz, K., … Mair, W. B. (2017). Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. Cell Metab, 26(6), 884-896.e5. https://doi.org/10.1016/j.cmet.2017.09.024
Weir, Heather J., Pallas Yao, Frank K. Huynh, Caroline C. Escoubas, Renata L. Goncalves, Kristopher Burkewitz, Raymond Laboy, Matthew D. Hirschey, and William B. Mair. “Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.Cell Metab 26, no. 6 (December 5, 2017): 884-896.e5. https://doi.org/10.1016/j.cmet.2017.09.024.
Weir HJ, Yao P, Huynh FK, Escoubas CC, Goncalves RL, Burkewitz K, et al. Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. Cell Metab. 2017 Dec 5;26(6):884-896.e5.
Weir, Heather J., et al. “Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.Cell Metab, vol. 26, no. 6, Dec. 2017, pp. 884-896.e5. Pubmed, doi:10.1016/j.cmet.2017.09.024.
Weir HJ, Yao P, Huynh FK, Escoubas CC, Goncalves RL, Burkewitz K, Laboy R, Hirschey MD, Mair WB. Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. Cell Metab. 2017 Dec 5;26(6):884-896.e5.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

December 5, 2017

Volume

26

Issue

6

Start / End Page

884 / 896.e5

Location

United States

Related Subject Headings

  • Protein Kinases
  • Peroxisomes
  • Models, Animal
  • Mitochondrial Dynamics
  • Mitochondria
  • Mice
  • Metabolomics
  • Longevity
  • Fatty Acids
  • Endocrinology & Metabolism