A multi-modal longevity protocol integrating lifestyle, supplements, and autologous pro-regenerative cell-conditioned media: a pilot study.

Introduction: Biological aging is a modifiable process contributing to functional decline and chronic disease risk. Multi-modal interventions targeting aging hallmarks have shown promise, yet human data integrating lifestyle, supplementation, and regenerative therapies remain limited. Methods: This single-arm, open-label pilot trial in 16 healthy adults aged 46-72 (14 completers) tested a 17-week multi-modal program integrating lifestyle optimization, targeted supplementation, and two intravenous infusions of autologous pro-regenerative cell-derived conditioned media (APRC-CM). Trial registration: ClinicalTrials.gov, NCT07322224. Results: The intervention improved clinical biomarkers and reduced biological-age measures (PhenoAge and an epigenetic DNA-methylation clock) despite the cohort's already healthy baseline (chronological age 59.3 years; PhenoAge 55.5 years; epigenetic age 57.9 years), consistent with a net reversal of biological age rather than merely a correction of age acceleration. PhenoAge declined by 2.0 years (p = 0.014), reaching 5.8 years below chronological age; epigenetic age decreased by 2.7 years (p = 0.003), widening the gap to 4.1 years. Exploratory response analysis revealed heterogeneity, with a larger-response subgroup showing a mean epigenetic-age reduction of 5.1 years versus 0.2 years in a smaller/no-response subgroup. Among baseline biomarkers, serum iron strongly predicted response: lower iron correlated with greater epigenetic-age reduction (r = 0.64; p = 0.013), identifying baseline iron status as a candidate prognostic biomarker of response. No adverse events were reported. Discussion: Such reductions in health-optimized individuals are notable and may indicate a lowering below expected norms rather than solely a correction of age acceleration. The observed response heterogeneity, together with baseline iron metabolism as a potential predictor of response, is hypothesis-generating and warrants validation in larger, controlled trials, particularly as this open-label, single-arm pilot lacked a control or sham comparator.