Reference - Detail
| RRC ID | 46277 |
|---|---|
| Author | Butler JA, Mishur RJ, Bhaskaran S, Rea SL. |
| Title | A metabolic signature for long life in the Caenorhabditis elegans Mit mutants. |
| Journal | Aging Cell |
| Abstract |
Mit mutations that disrupt function of the mitochondrial electron transport chain can, inexplicably, prolong Caenorhabditis elegans lifespan. In this study we use a metabolomics approach to identify an ensemble of mitochondrial-derived α-ketoacids and α-hydroxyacids that are produced by long-lived Mit mutants but not by other long-lived mutants or by short-lived mitochondrial mutants. We show that accumulation of these compounds is dependent on concerted inhibition of three α-ketoacid dehydrogenases that share dihydrolipoamide dehydrogenase (DLD) as a common subunit, a protein previously linked in humans with increased risk of Alzheimer's disease. When the expression of DLD in wild-type animals was reduced using RNA interference we observed an unprecedented effect on lifespan - as RNAi dosage was increased lifespan was significantly shortened, but, at higher doses, it was significantly lengthened, suggesting that DLD plays a unique role in modulating length of life. Our findings provide novel insight into the origin of the Mit phenotype. |
| Volume | 12(1) |
| Pages | 130-8 |
| Published | 2013-2-1 |
| DOI | 10.1111/acel.12029 |
| PMID | 23173729 |
| PMC | PMC3552119 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Dihydrolipoamide Dehydrogenase / genetics Dihydrolipoamide Dehydrogenase / metabolism Longevity / genetics Longevity / physiology* Mutation* |
| IF | 7.238 |
| Times Cited | 40 |
| WOS Category | GERIATRICS & GERONTOLOGY CELL BIOLOGY |
| 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 | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2258 tm2285 |