In recent years a number of different groups have generated aging clocks intended to assess distinct biological ages for different organs and systems in the body, OrganAge being one example. Data from large human populations suggests that different organs and systems can age at somewhat different rates. Here, researchers use UK Biobank data to generate a novel organ specific proteomic clock, producing similar data to the earlier OrganAge research program.
Organ-specific plasma protein signatures identified via proteomics profiling could be used to quantitatively track organ aging. However, the genetic determinants and molecular mechanisms underlying the organ-specific aging process remain poorly characterized. Here we integrated large-scale plasma proteomic and genomic data from 51,936 UK Biobank participants to uncover the genetic architectures underlying aging across 13 organs.
We identified 119 genetic loci associated with organ aging, including 27 shared across multiple organs, and prioritized 554 risk genes involved in organ-relevant biological pathways, such as T cell-mediated immunity in immune aging. Causal inference analyses indicated that accelerated heart and muscle aging increase the risk of heart failure, whereas kidney aging contributes to hypertension. Moreover, smoking initiation was positively linked to the aging of the lung, intestine, kidney, and stomach. These findings establish a genetic foundation for understanding organ-specific aging and provide insights for promoting healthy longevity.
