Reference - Detail
| RRC ID | 53232 |
|---|---|
| Author | Mishur RJ, Khan M, Munkácsy E, Sharma L, Bokov A, Beam H, Radetskaya O, Borror M, Lane R, Bai Y, Rea SL. |
| Title | Mitochondrial metabolites extend lifespan. |
| Journal | Aging Cell |
| Abstract |
Disruption of mitochondrial respiration in the nematode Caenorhabditis elegans can extend lifespan. We previously showed that long-lived respiratory mutants generate elevated amounts of α-ketoacids. These compounds are structurally related to α-ketoglutarate, suggesting they may be biologically relevant. Here, we show that provision of several such metabolites to wild-type worms is sufficient to extend their life. At least one mode of action is through stabilization of hypoxia-inducible factor-1 (HIF-1). We also find that an α-ketoglutarate mimetic, 2,4-pyridinedicarboxylic acid (2,4-PDA), is alone sufficient to increase the lifespan of wild-type worms and this effect is blocked by removal of HIF-1. HIF-1 is constitutively active in isp-1(qm150) Mit mutants, and accordingly, 2,4-PDA does not further increase their lifespan. Incubation of mouse 3T3-L1 fibroblasts with life-prolonging α-ketoacids also results in HIF-1α stabilization. We propose that metabolites that build up following mitochondrial respiratory dysfunction form a novel mode of cell signaling that acts to regulate lifespan. |
| Volume | 15(2) |
| Pages | 336-48 |
| Published | 2016-4-1 |
| DOI | 10.1111/acel.12439 |
| PMID | 26729005 |
| PMC | PMC4783347 |
| MeSH | 3T3-L1 Cells Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Ketoglutaric Acids / metabolism* Longevity / physiology* Mice Mitochondria / metabolism* |
| IF | 7.238 |
| Times Cited | 28 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 22 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2285 |