3. Omics Clocks Are Practical Projections of Aging, Not Direct Measures of the Deleteriome

While aging is the accumulation of damage, we typically measure biological age using omics-based clocks, which are statistical projections of molecular state trained to predict chronological time and/or health outcomes and include damage along with other age-related changes. At present, we do not know how clock outputs map onto specific deleteriome components, what major components they systematically miss, or whether the same clock features reflect the same underlying biology across species with very different lifespans and maintenance architectures. In practice, we are using one construct to define the process (damage/deleteriome) and a different, empirically convenient construct to locate an organism along that process (age based on aging clocks). A related issue is that aging clocks often mix age-related deleterious changes and responses to these changes; only recently have causality-enriched clocks emerged, including DamAge and AdaptAge (64). Bridging these gaps will require tools that directly quantify (or provide robust, mechanism-anchored proxies for) key deleteriome components, so that clock readouts become interpretable, comparable across tissues and species, and ultimately actionable.