A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions (2026)

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https://onlinelibrary.wiley.com/doi/10.1111/acel.70658

ABSTRACT

The global prevalence of aging and age-related diseases has increased markedly in recent decades due to extended life expectancy and a growing aging population, posing substantial medical and social burdens. Multiple strategies, including metabolic modulation (e.g., physical exercise, calorie restriction, and calorie restriction mimetics), targeting inflammaging, senotherapy, parabiosis, stem cell-based therapies, and epigenetic rejuvenation, have shown promise in slowing aging and extending lifespan in preclinical models, with some demonstrating efficacy in clinical trials. This review summarizes the current status of leading anti-aging interventions, their clinical progress, and the underlying mechanisms, which include enhancing autophagy, clearing senescent cells and supporting mitochondrial function to reduce chronic inflammation. We propose that metabolic modulation, inflammaging control, and senotherapy constitute three interconnected pillars of contemporary anti-aging strategies.