Interventions that prolong multidimensional healthspan in humans: a systematic review of randomized controlled trials

Maximizing healthspan, the period of life spent in good health, is a public health priority. This review aimed to summarize the current evidence from randomized controlled trials on interventions that can prolong healthspan in humans. The specific focus was on multidimensional person-centered outcomes, which reflect functioning rather than disease, such as intrinsic capacity and quality of life. This review was registered (CRD420251015780) and conducted with adherence to the PRISMA guidelines. MEDLINE, EMBASE, and grey literature were systematically searched for studies evaluating interventions that improve intrinsic capacity or quality of life. The search included articles published up to October 16, 2025. Of 1960 publications identified, 15 articles (4656 participants) met the inclusion criteria. There was high heterogeneity between the included studies in terms of the interventions examined, which varied from exercise alone (7 studies) to multidomain interventions (6 studies, all of which included an exercise component), daily oral supplementation (2 studies), or caloric restriction (1 study). Overall, 11 studies reported that exercise or multidimensional intervention (which included an exercise component) improved intrinsic capacity and quality of life. However, due to the small number of studies and heterogeneity, no conclusion could be drawn regarding other interventions. Therefore there is some evidence that exercise could extend intrinsic capacity and quality of life, either aerobic or resistance training alone, or a combination of different types of exercise; but further research is required to evaluate the effect of other interventions that may prolong healthspan across more diverse populations.