論文 - 詳細
| RRC ID | 76287 |
|---|---|
| 著者 | Savini M, Folick A, Lee YT, Jin F, Cuevas A, Tillman MC, Duffy JD, Zhao Q, Neve IA, Hu PW, Yu Y, Zhang Q, Ye Y, Mair WB, Wang J, Han L, Ortlund EA, Wang MC. |
| タイトル | Lysosome lipid signalling from the periphery to neurons regulates longevity. |
| ジャーナル | Nat Cell Biol |
| Abstract |
Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in ageing-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate ageing remains unclear. Here we report a fat-to-neuron lipid signalling pathway induced by lysosomal metabolism and its longevity-promoting role in Caenorhabditis elegans. We discovered that induced lysosomal lipolysis in peripheral fat storage tissue upregulates the neuropeptide signalling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a specific polyunsaturated fatty acid, dihomo-γ-linolenic acid, and LBP-3 lipid chaperone protein transported from the fat storage tissue to neurons. LBP-3 binds to dihomo-γ-linolenic acid, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signalling hub to coordinate metabolism and ageing, and lysosomal signalling mediated inter-tissue communication in promoting longevity. |
| 巻・号 | 24(6) |
| ページ | 906-916 |
| 公開日 | 2022-6-1 |
| DOI | 10.1038/s41556-022-00926-8 |
| PII | 10.1038/s41556-022-00926-8 |
| PMID | 35681008 |
| PMC | PMC9203275 |
| MeSH | 8,11,14-Eicosatrienoic Acid / metabolism Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Longevity / genetics Lysosomes / metabolism Neurons / metabolism Neuropeptides* / metabolism |
| 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 | 188 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.7 |
| リソース情報 | |
| 線虫 | tm1011 |