Extending Healthspan via GLP-1 Receptor Agonist: Insights and Perspectives

Aging is characterized by a progressive decline in physiological function, an increased risk of chronic diseases, and multiple molecular and cellular alterations, including inflammation, oxidative stress, and mitochondrial dysfunction(definition). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes and obesity, may modulate pathways associated with the telomere(definition) attrition, cellular senescence(definition))." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">hallmarks of aging(definition). This review aims to summarize the mechanistic and therapeutic evidence for GLP-1 RAs in targeting key aging processes and their potential to restore cellular homeostasis and enhance healthspan(definition). A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025. Both preclinical and clinical studies were included if they evaluated the effects of GLP-1 RAs on the major biological processes encompassed by the 12 hallmarks of aging, such as mitochondrial dysfunction, insulin resistance, dysbiosis, inflammaging(definition), autophagy(definition), proteostasis(definition), and genomic stability. Data were analyzed narratively to elucidate potential mechanisms and translational relevance. Evidence from animal and human studies demonstrates that GLP-1 RAs improve mitochondrial function, reduce oxidative stress, attenuate chronic inflammation, and enhance autophagic activity. Additionally, they modulate nutrient-sensing pathways and metabolic processes, thereby improving cellular resilience. Preclinical studies indicate neuroprotective, cardioprotective, and hepatoprotective effects, while emerging clinical data support improvements in metabolic and inflammatory profiles in older adults. Taken together, GLP-1 RAs exert pleiotropic effects across all 12 hallmarks of aging. Although long-term safety and efficacy require further evaluation, current evidence positions GLP-1 RAs as promising therapeutic agents in translational geroscience, with the potential to mitigate age-related physiological decline and promote a longer, healthier lifespan.