Bioactive Compounds from Medicinal and Edible Plants for Anti-Aging: A Systematic Review of Molecular Mechanisms, Delivery Systems, and Clinical Evidence.

Aging-related decline involves changes in oxidative stress, inflammation, mitochondrial function, telomere maintenance, metabolic regulation, and extracellular matrix homeostasis. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and searched PubMed, Scopus, Embase, and Web of Science for English-language studies published from 1993 to 2025. Twelve primary studies met the eligibility criteria: four randomized clinical studies, four animal studies, one in vitro mechanistic study, and three delivery-system/formulation studies. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2), the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool, and a review-specific domain-based checklist informed by the National Toxicology Program/Office of Health Assessment and Translation framework. Representative compounds, including resveratrol, astragaloside IV, Ganoderma lucidum polysaccharide, epigallocatechin-3-gallate (EGCG) and betulinic acid, were associated with mitochondrial regulation, antioxidant defense, cytoskeletal stability, gut-brain signaling, extracellular-matrix protection, and longevity-related signaling. Nanoliposomes and poly(lactic-co-glycolic acid) (PLGA) nanoparticles improved selected stability, penetration, and pharmacokinetic outcomes. However, the evidence base was heterogeneous and predominantly preclinical; human evidence was limited to four relatively small studies, and certainty ranged from moderate to very low. The findings support mechanistic and translational potential but do not establish definitive anti-aging efficacy in humans.