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Natural Small Molecules Targeting Oxidative Stress and Redox Homeostasis in Aging: Mechanisms and Therapeutic
Yu Li1,2, Haodong Wu1,2, Zeyi Zhang1,2
1School of Medicine, Xiamen University, Xiamen 361102, China.
Abstract:
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.
Insights
Medicinal plant compounds show promise for anti-ageing by targeting oxidative stress and redox balance. However, more rigorous clinical studies are needed to validate their effectiveness and ensure safe application in aging populations.
Area of Science:
- Gerontology and Longevity Research
- Molecular Biology and Biochemistry
- Pharmacology and Natural Products
Background:
- The global population is rapidly aging, with individuals over 60 projected to exceed 2 billion by 2050.
- Aging is a significant risk factor for chronic diseases, increasingly viewed as a modifiable biological process.
- Oxidative stress, driven by reactive oxygen and nitrogen species (ROS/RNS), is a key factor in aging, damaging cellular components and exacerbating age-related dysfunction.
Purpose of the Study:
- To review and analyze recent research on medicinal plant-derived monomers with anti-aging potential.
- To evaluate the role of these compounds in modulating oxidative stress and redox homeostasis.
- To assess the strength, consistency, and translational relevance of current evidence.
Main Methods:
- Systematic review of studies published in the last decade focusing on plant-derived monomers and anti-aging effects.
- Comparison of major redox-centered pathways, molecular targets, model systems, and outcome measures.
- Critical evaluation of evidence considering strength, consistency, and translational relevance.
Main Results:
- Medicinal plants offer monomers that act as direct antioxidants and restore redox balance by modulating key signaling pathways (Nrf2/FOXO/SIRT1, AMPK/mTOR, NF-κB).
- Evidence for anti-aging effects is currently heterogeneous, with limited reliable clinical validation.
- Key limitations include model dependence, variable bioavailability, uncertain dose-exposure relationships, and a lack of robust clinical trials.
Conclusions:
- Plant-derived monomers targeting oxidative stress and redox homeostasis present a potential strategy for multi-disease benefits in aging.
- Significant challenges remain, including the need for improved bioavailability and well-designed clinical studies.
- Future research should focus on mechanistic understanding and translational validation for evidence-based application in aging populations.
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