Organ-Specific Proteomic Aging Clocks Reveal Complexities Underlying the Healthy Drinking Paradox

The "healthy drinking" paradox refers to situations where alcohol consumption is misleadingly associated with better health outcomes, a pattern frequently observed in observational studies that are prone to a range of confounding factors. Some recent studies developing organ-specific proteomic aging clocks report that alcohol consumption is linked to slower aging in select organs, even as it accelerates aging in others, thus echoing this paradox, with substantial discrepancies across such studies. In this Perspective, I summarize findings to date, discuss potential reasons for these contradictory results, such as differences in clock construction, alcohol phenotyping, and confounding control across studies, and highlight both the limitations and promise of organ-specific clocks for studying epidemiologically challenging traits such as alcohol consumption. Taken together, these findings call for careful interpretation of observational studies linking alcohol consumption to systemic and organ-specific biological aging, which may, if taken at face value, understate the known damage that alcohol causes to human health. Further work comparing organ-specific clocks developed across different studies from a biological standpoint is needed to fully decipher the true effects of alcohol consumption, alongside research applying aging clocks to alcohol consumption within more advanced epidemiological designs and across different dimensions of aging (chronological age vs. mortality).