28. Aging Is Irreversible, but Biological Age Can Sometimes be Reduced or Reset

Aging, framed as a time history of damage accumulation, cannot be undone (e.g., many age-related changes cannot be reversed), whereas biological age, as an operational measure, can in principle be partially reset, as some deleteriome components can be repaired, removed, or diluted. However, such a rejuvenated state would not be the same state compared to when this organism was chronologically younger, as some deleteriome components are not reversible. Therefore, age reversal should not be interpreted as a return to a prior state or as a reversal of aging. Evidence for a reversal of biological age comes from embryonic rejuvenation, heterochronic parabiosis, and heterochronic transplantation data as well as from interventions that reduce biological age and cases of the reversal of biological age first accelerated by severe stress (12, 14–16, 57, 58). At the cell level, age reversal can be achieved by cell reprogramming to induced pluripotent stem cells. The practical question is not whether we can fully reverse the aging process (we cannot), but which components of the system can be pushed back far enough to produce durable health and survival benefits, without loss of cellular identity or increased cancer risk.