Tissue- and Organ-Related Molecular Aging Clocks: Measurement, Interpretation, and Translational Validation

Biological age measures are increasingly derived from target tissues, proximal fluids, and circulating signals, but whether they represent aging of a specific organ remains uncertain. Differences in sample source, biological resolution, and validation make predicted ages and age gaps from these pathways non-interchangeable. This critical narrative review compares representative molecular clocks of the central nervous system and peripheral organs and introduces the source, resolution, and validation framework, abbreviated as S-R-V, to assess the organ attribution and translational claims supported by each model. Across organs, molecular age measures were linked to different aspects of organ state and biological context. Chronological age prediction was more consistently demonstrated than alignment with organ pathology or function. Age gaps may reflect varying contributions from organ-related signals, cellular composition, systemic influences, disease-related remodeling, and technical or modeling effects. Correlations among organ age gaps represented dependence among model outputs and did not establish communication, temporal ordering, or causality between organs. Evidence was concentrated in model development, external replication, and cross-sectional disease association, while prospective prediction, longitudinal responsiveness, and clinical utility were less developed. Future studies should pair target tissue, proximal fluid, and circulating measures with organ pathology or function in the same participants and use repeated measurements to determine whether accessible measures track within-person change. By matching measurement context to validation evidence, S-R-V can help define when organ age measures support risk stratification, longitudinal monitoring, or intervention evaluation.