A systematic review of 15 randomized controlled trials covering 4656 mostly older adults finds that exercise, either on its own or bundled into a multidomain program, is the single intervention with reasonably consistent evidence for improving multidimensional healthspan, measured as intrinsic capacity and quality of life. Caloric restriction, omega-3, and NMN supplementation each showed some signal, but each rested on only one or two trials, so no firm conclusion is possible. The authors are careful to note that even where exercise worked, the effect sizes were generally small and the clinical meaningfulness is uncertain.
For decades the longevity conversation has been dominated by the search for a molecule, some metformin, rapamycin, or resveratrol style compound that could reset the aging clock. This review, from Monash University and the University of Basel, quietly reframes the question. Instead of asking what extends lifespan in a petri dish or a mouse, it asks a harder and more human question: which interventions actually keep people functioning well, and what does the gold-standard trial evidence say?
The team searched the major medical databases through October 2025 and found only 15 randomized controlled trials that measured healthspan the way it arguably matters most, as a whole-person composite rather than a single disease. They used two lenses. The first, intrinsic capacity, sums a person’s physical and mental abilities across cognition, mobility, vitality, psychological state, and the senses. The second, quality of life, captures how people actually feel about their own wellbeing.
The headline finding is almost old-fashioned. Movement wins. Eleven of thirteen trials that included an exercise component reported better intrinsic capacity or quality of life in the intervention group. Aerobic training worked, resistance training worked, and so did mixed multicomponent programs that layered in balance and flexibility. Frail hospitalized patients and community-dwelling elders alike benefited. The one exercise trial that flopped was a single week of hiking, which is likely too short to move the needle.
The more fashionable interventions fared worse under scrutiny. A rigorous two-year 25 percent caloric restriction trial did improve self-rated general health. A 60-day NMN supplement trial improved quality of life scores. But each of these is a lone study, and the authors refuse to overclaim. The pattern that survives is unglamorous: sustained physical activity, ideally started before old age and maintained for months to years, is the best-evidenced route to more years lived in good working order.
There is an honesty here worth flagging. The authors did not run a meta-analysis because the trials were too heterogeneous, and they concede the exercise effects, while statistically real, are mostly small. This is a map of what we can and cannot yet claim, not a victory lap.
Actionable Insights
The one intervention with repeatable trial support is exercise, so the practical takeaway is to train consistently and for the long haul, not to just chase supplements. The magnitudes are modest but real. In frail cognitively impaired elders, a 12-week home-based multicomponent program (Vivifrail) raised an intrinsic capacity z-score by 0.48 standard deviations, which is a small-to-moderate effect roughly equivalent to Cohen’s d of 0.48. In older adults with memory concerns, six months of aerobic or resistance training each lifted intrinsic capacity by about 0.18 to 0.19 standard deviations, a small effect that faded toward non-significance by one year once training stopped, underscoring that the benefit is use-it-or-lose-it. Combining aerobic plus resistance in the same session showed no added benefit and sometimes less, hinting at a dose or fatigue ceiling. Two years of 25 percent caloric restriction improved SF-36 general health by about 6.5 points on a 100-point scale, an approximate d of 0.3. A 60-day NMN trial produced the largest standardized quality-of-life effect (d roughly 0.6 to 0.9), but from a single small study that needs replication before acting on it. Net message: exercise is the safe bet, dietary and supplement interventions are promising but unproven.
Context and Source
- Open access paper: Interventions that prolong multidimensional healthspan in humans: a systematic review of randomized controlled trials.
- Authors and institutions: Haoxin Tina Zheng, Aung Zaw Zaw Phyo, Claire McCubbin, Zimu Wu, and Joanne Ryan of the School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; and Heike A. Bischoff-Ferrari of the Department of Acute Aging Medicine Felix Platter, University of Basel, Switzerland.
- Country: Australia (lead institution), with Switzerland.
- Journal: The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences (Oxford University Press, on behalf of the Gerontological Society of America).
- Impact evaluation: The most recent Journal Impact Factor is 3.8 (2024 JIF, released in the 2025 update; the journal’s recent five-year range runs roughly 3.8 to 6.6, and its Scopus CiteScore is about 8.2). Using the JIF: the impact score of this journal is 3.8, evaluated against a typical high-end range of 0 to 60+ for top general science, therefore this is a Low-to-Medium impact journal on that absolute scale. Context matters here though: within its own field of gerontology it ranks approximately 4th of 49 journals, placing it firmly in the top quartile and making it one of the most respected specialist venues in aging research