| RRC ID |
51508
|
| 著者 |
Weir HJ, Yao P, Huynh FK, Escoubas CC, Goncalves RL, Burkewitz K, Laboy R, Hirschey MD, Mair WB.
|
| タイトル |
Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.
|
| ジャーナル |
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.
|
| 巻・号 |
26(6)
|
| ページ |
884-896.e5
|
| 公開日 |
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
|
| 引用数 |
79
|
| リソース情報 |
| 線虫 |
tm1107
tm1108
tm1133 |
