A new photoplethysmography-based arterial aging clock developed by our lab
In our new preprint, we present the largest genomic exploration of arterial aging to date, leveraging photoplethysmography (PPG)–derived pulse waveforms from 115,000 UK Biobank participants.
While aging of the large arteries, characterized by progressive stiffness, is a well-established risk factor for cardiovascular disease, the mechanisms driving this pathology remain poorly understood. We lack targeted interventions that could slow or prevent arterial aging.
Using PPG waveforms and blood pressure measurements, we developed an arterial aging clock that is scalable, associated with known vascular risk factors, and predictive of future cardiovascular events independently of chronological age.
We then performed GWAS and rare variant burden analyses to identify genetic signals associated with arterial aging. We found 60 loci in GWAS and 5 genes in rare variant analyses. Of them, 34 loci were novel, not previously linked to vascular traits. The expression of nearby genes was strongly enriched in human arterial tissues.
Transcriptome-wide association analyses using RNA-seq data from human aorta and coronary arteries identified 28 genes, including RSG19 and ULK4, whose expression likely drives these genetic associations. Single-cell transcriptomics revealed strong enrichment of these genes in fibroblasts, implicating fibrotic remodeling mechanisms in arterial aging.
Rare variant burden testing further implicated damaging variants in COL21A1, LMNA, TP53BP2, RXRB, and FLOT2, also converging on extracellular matrix remodeling and fibrosis-related pathways.
Great work by PhD student Lingling Xu and the rest of the team!
https://www.medrxiv.org/content/10.1101/2025.11.15.25340310v1
