29. Rejuvenation Is a Measurable Reduction in Biological Age

Rejuvenation is a persistent decrease in biological age from a prior state, defined as a net reduction of deleteriome burden (59, 60). It is not the process opposite to aging (aging is irreversible), and it is not merely feeling better nor necessarily reversing every component; rather, it is a measurable move of an organism’s biological age to a lower state. Embryogenesis contains a natural rejuvenation event (14–16), demonstrating that profound age resetting is biologically possible. In adults, rejuvenation may occur via activated repair, removal, or dilution of deleteriome components, replacement of failing components, heterochronic parabiosis, and possibly through cell reprogramming and systemic remodeling (61). When claimed at the level of organisms (e.g., in older adults), it is useful to evaluate whether it truly reduces risk-relevant deterioration below the pretreatment level, beyond changes expected in a matched untreated group. It is also important to test whether the shift restores function rather than merely erasing adaptive responses to accumulated burden and whether the observed rejuvenation persists (observed over prolonged periods of time). More generally, besides omics readouts, rejuvenation claims should be anchored to interpretable states via robust changes in deleteriome, function, resilience, and/or deficits.