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A rare collagen gene mutation found in centenarians may extend lifespan by enhancing extracellular signaling and innate immunity.
The Discovery:
Researchers modeled a human centenarian SNP in the collagen gene COL25A1 using its C. elegans ortholog col-99. The S106L mutation significantly extended lifespan by ~26%, without improving stress resistance. Instead, it altered collagen processing, boosting immune-related pathways and revealing a novel mechanism of longevity driven by extracellular matrix remodeling.
The Science:
A centenarian-linked SNP in COL25A1 (S116L) was mapped to col-99 (S106L) in C. elegans
Mutant col-99(S106L) animals lived ~26% longer than wild-type
Lifespan extension was independent of stress resistance and linked to changes in furin-mediated cleavage
Expression of the cleaved extracellular domain alone was sufficient to extend lifespan by ~11%
The mutation reduces phosphorylation at a site near the cleavage domain, enabling greater shedding
Transcriptomics showed innate immune genes upregulated, including T24B8.5, argk-1, and atf-7
Lifespan gains required tir-1, osm-9, pmk-1 (p38 MAPK), and yap-1, but not ATF-7 or DAF-16
The pathway bypasses canonical immune signaling, linking collagen remodeling to immune activation via YAP-1
Your Action:
Support your extracellular matrix and immunity through consistent strength training and nutrient-rich whole foods. Look for ways to promote tissue integrity and mechanical stimulation. Stay tuned as collagen signaling becomes a new frontier in longevity.
Bottom Line:
A centenarian collagen variant triggers extracellular signaling and immune activation to extend lifespan without replacing the gene entirely.
Source:
A centenarian single nucleotide polymorphism in collagen gene COL25A1 promotes longevity in C. elegans, npj Aging, Anita Goyala et al.
https://doi.org/10.1038/s41514-025-00264-7
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Disclaimer:
This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.