Short-term responsiveness of DNA methylation–based aging biomarkers to a multimodal intervention comprising exercise and dietary guidance involving daily consumption of yogurt containing Bifidobacterium longum BB536: an exploratory randomized controlled trial

Aging-related chronic diseases are driven by multiple mechanisms, motivating efforts to develop feasible interventions that can attenuate biological aging. DNA methylation-based epigenetic clocks, particularly measures of the pace of aging such as DunedinPACE, are sensitive to relatively short-term changes in aging processes. However, evidence from randomized controlled trials remains limited. We conducted a randomized controlled trial to test a 12-week multimodal lifestyle intervention comprising exercise and dietary guidance involving daily consumption of yogurt containing Bifidobacterium longum BB536 on DNA methylation-based aging measures in overweight men aged ≥50 years. The intervention group exhibited a significant deceleration in DunedinPACE, corresponding to an estimated 2.2% slower pace of aging, whereas no meaningful change was observed in the control group. Exploratory analyses further identified a significant reduction in DNAmCystatinC, a renal-related GrimAge surrogate marker, while no clock within the biological age remained significant after false discovery rate correction. These findings suggest that a feasible, multimodal lifestyle intervention—including exercise and dietary guidance with daily consumption of yogurt containing Bifidobacterium longum BB536—may be associated with short-term changes in selected DNA methylation-based aging measures. Larger and longer-term studies are warranted to confirm the durability and clinical relevance. This clinical trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000057293).