論文 - 詳細
| RRC ID | 80826 |
|---|---|
| 著者 | Possik E, Klein LL, Sanjab P, Zhu R, Côté L, Bai Y, Zhang D, Sun H, Al-Mass A, Oppong A, Ahmad R, Parker A, Madiraju SRM, Al-Mulla F, Prentki M. |
| タイトル | Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans. |
| ジャーナル | Nat Commun |
| Abstract |
Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients. |
| 巻・号 | 14(1) |
| ページ | 5214 |
| 公開日 | 2023-8-25 |
| DOI | 10.1038/s41467-023-40857-y |
| PII | 10.1038/s41467-023-40857-y |
| PMID | 37626039 |
| PMC | PMC10457390 |
| MeSH | AMP-Activated Protein Kinases / genetics Animals Autophagy / genetics Basic Helix-Loop-Helix Transcription Factors Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins* / genetics Glycerol Glycogen Healthy Aging* Phosphates Phosphoric Monoester Hydrolases |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1978 |