Fig. 9: ‘Anti-aging’ effects were frequently age-independent in nature.

The schematic illustrates major scenarios by which PAAIs could influence aging phenotypes. First, interventions could have no measurable effect on a set of phenotypes or even accentuate age-dependent phenotypic change. ASPs countered by an intervention could be influenced in ways consistent with a targeting of the mechanisms underlying age-dependent phenotypic change: In this case, PAAI effects should become apparent only after the onset of aging-associated phenotypic change, but not at younger ages (rate effect). PAAI effects at a young age (prior to the age when age-dependent phenotypic change becomes first detectable) indicate that it is not the age-dependent change that is being targeted (baseline effect). Although our studies revealed examples of both rate and baseline effects, many ‘anti-aging’ effects fell into the latter category (age-independent effects that do not provide evidence for a slowed aging rate). Ignoring this distinction would lead to a substantial overestimation of the extent by which PAAIs slow the aging process. Created with BioRender.com.