Inferring organ aging, hallmark of aging and senescence scores from blood and facial photographs

Organ aging unveils as a unique process, with distinct rates across various bodily systems. This drove the creation of organ-specific aging clocks. However, directly measuring organ aging in humans is difficult. Our study developed these clocks using blood and tissue RNA sequencing data from the GTEx project. We discovered significant diversity in both the intensity of aging markers and their ability to predict organ age and scores from blood.

Pathway analysis revealed that these clocks are heavily influenced by specific biological processes unique to each tissue. We identified multi-organ aging modules and found that organ age features are causally linked through transcriptomic interactions between organs and blood. Given the known role of cellular senescence in tissue dysfunction during aging, we expanded our framework to estimate organ-level senescence and other aging hallmarks.

By evaluating senescence-associated and hallmark-associated gene sets, we derived organ-specific senescence and hallmark scores, which could be predicted from blood transcriptomes. Our research extends these models to explore blood methylation patterns and facial photographs as potential non-invasive substitutes for blood-organ age and scores in independent cohorts, such as the Edifice Health and Health and Retirement Study.

These findings establish a multi-modal approach for predicting organ-specific aging and senescence from minimally invasive data.