Natural Small Molecules Targeting Oxidative Stress and Redox Homeostasis in Aging: Mechanisms and Therapeutic Potential.

The global population is ageing rapidly; adults aged ≥ 60 years are projected to exceed 2 billion by 2050. Ageing is a major risk factor for chronic and degenerative disorders and is increasingly viewed as a modifiable biological program. Oxidative stress is a central driver: sustained ROS/RNS accumulation damages lipids, proteins and nucleic acids and amplifies mitochondrial dysfunction, inflammaging, cellular senescence, impaired autophagy and telomere instability. Targeting these shared mechanisms may therefore deliver multi-disease benefits beyond single-disease therapy. Medicinal plants provide chemically defined monomers that can act as direct antioxidants and, more importantly, restore redox homeostasis by modulating conserved signaling axes, including Nrf2/FOXO/SIRT1, AMPK/mTOR and NF-κB. However, the current evidence base remains highly heterogeneous, and reliable clinical validation is still limited. In this review, we summarize studies published over the last decade on medicinal plant-derived monomers with reported anti-ageing relevance in the context of oxidative stress and redox homeostasis. We compare major redox-centered pathways, molecular targets, model systems, and outcome measures, and evaluate the evidence with attention to its strength, consistency, and translational relevance. Particular emphasis is placed on current limitations, including model dependence, variable bioavailability, uncertain dose-exposure relationships, and the lack of well-designed clinical studies. These considerations are intended to provide a more cautious and evidence-based framework for future mechanistic and translational research.