Reference - Detail
| RRC ID | 87982 |
|---|---|
| Author | Goyala A, Statzer C, Park JYC, Neundorf I, MacArthur MR, Gebauer JM, Ewald CY. |
| Title | A centenarian single nucleotide polymorphism in collagen gene COL25A1 promotes longevity in C. elegans. |
| Journal | 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. |
| Volume | 11(1) |
| Pages | 81 |
| Published | 2025-9-30 |
| DOI | 10.1038/s41514-025-00264-7 |
| PII | 10.1038/s41514-025-00264-7 |
| PMID | 41027912 |
| PMC | PMC12484612 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1416 |