論文 - 詳細
| RRC ID | 87982 |
|---|---|
| 著者 | Goyala A, Statzer C, Park JYC, Neundorf I, MacArthur MR, Gebauer JM, Ewald CY. |
| タイトル | A centenarian single nucleotide polymorphism in collagen gene COL25A1 promotes longevity in C. elegans. |
| ジャーナル | NPJ Aging |
| Abstract |
Before human genome sequencing, a genome-wide study of sibling centenarian pairs identified a longevity-associated locus on chromosome 4. Here, we mapped the genes in this locus and identified a collagen gene, COL25A1. Introducing an SNP linked to longevity that changes a serine predicted to be phosphorylated to leucine in COL25A1, into col-99, the C. elegans ortholog, extended lifespan. These col-99(gk694263[S106L]) SNP-mutants exhibited enhanced innate immune-related transcriptional responses, and their lifespan extension was abolished by inhibiting the p38 MAPK pathway. YAP-1, a transcriptional co-activator responsive to extracellular matrix changes, was essential for this longevity. Mechanistically, we find that this SNP modifies furin-mediated cleavage of this transmembrane collagen in vitro, and expressing the cleaved extracellular domain of COL-99 alone was sufficient to prolong C. elegans' lifespan. These findings reveal a potential mechanism by which a human centenarian-associated SNP in COL25A1 influences furin cleavage and shedding of the collagen ectodomain to promote healthy longevity. |
| 巻・号 | 11(1) |
| ページ | 81 |
| 公開日 | 2025-9-30 |
| DOI | 10.1038/s41514-025-00264-7 |
| PII | 10.1038/s41514-025-00264-7 |
| PMID | 41027912 |
| PMC | PMC12484612 |
| 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 | 5 |
| 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 | tm1416 |