Mendelian randomization study implicates inflammaging biomarkers in retinal vasculature, cardiovascular diseases, and longevity.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 41134885.
- Also identified by DOI 10.1126/sciadv.adu1985 and PMC identifier 12551708.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension (<i>D</i><sub>f</sub>) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of <i>D</i><sub>f</sub> on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near <i>DAAM1</i>. We found negative genetic correlations between <i>D</i><sub>f</sub> and cardiovascular disease, stroke, and inflammation but a positive correlation with life span. By combining the genetic determinants of 1159 circulating proteins from the Prospective Urban and Rural Epidemiological cohort with those of <i>D</i><sub>f</sub> using Mendelian randomization, we identified eight causal mediators, including MMP12 and IgG-Fc receptor IIb, which link higher inflammation to lower <i>D</i><sub>f</sub>, increased cardiovascular disease risk, and shorter life span. These results extend our understanding of the biological pathways underlying aging processes and inform targets to prevention and treatment.
Medical subject headings
- Mendelian Randomization Analysis
- Cardiovascular Diseases
- Biomarkers
- Longevity
- Inflammation
- Retinal Vessels
- Aging