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🔬TODAY’S BREAKTHROUGH
Frailty is one of aging’s clearest warning signs. A massive genetic study now reveals dozens of new variants and proteins that shape this complex syndrome.
The Discovery:
By analyzing data from over 900,000 people in FinnGen and UK Biobank, researchers discovered 53 genetic variants linked to frailty, 45 of them novel. Integrating proteomics, they identified key proteins like APOE, MET, and CGREF1 that influence frailty risk. These insights show how genes and circulating proteins together drive resilience, or vulnerability in aging.
The Science:
Scale: GWAS of 500,737 FinnGen participants, replicated in 407,463 UK Biobank participants.
Findings: 53 lead genetic variants tied to frailty, including CHST9, ILRUN, KHK, MET, APOE, CGREF1, PPP6C.
Proteomics link: Plasma levels of MET, CGREF1, APOE, NECTIN2 strongly associated with frailty risk.
Pathways: Signals enriched in nervous system function, lipid metabolism, and cell adhesion.
Polygenic risk scores: Frailty genetics predicted early-onset frailty, mortality, and hospitalizations.
Heritability: Frailty shown to be ~6% heritable, confirming polygenic nature.
Your Action:
Frailty is influenced by genetics, but environment and lifestyle remain powerful levers. Reduce risk by building muscle strength, staying active, eating nutrient-rich foods, and avoiding inflammation drivers like smoking and processed diets. These behaviors counterbalance genetic vulnerability.
Bottom Line:
Frailty has a genetic and proteomic blueprint, knowledge that could guide precision strategies to extend resilience in aging.
Source:
Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty. Nature Aging. Mak JKL, Qin C, Krüger M, Kuukka A, Hägg S, Jylhävä J, et al.
https://doi.org/10.1038/s43587-025-00925-y
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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.