Free Radicals (ROS)
Molecules with unpaired electrons — necessary for life in controlled doses
Definition
Free radicals are molecules or atoms with an unpaired electron in their outer orbital, making them highly reactive. In biology, the most relevant are reactive oxygen species (ROS) and nitrogen species (RNS): superoxide (O₂•⁻), hydrogen peroxide (H₂O₂), hydroxyl radical (•OH), nitric oxide (•NO), and peroxynitrite (ONOO⁻). Although popularly demonised, they are essential for cellular signalling, immune defence (phagocytic cells use them to destroy pathogens), and exercise adaptation (mitohormesis).
Detailed explanation
Main sources of endogenous ROS:
Mitochondrial respiratory chain: complexes I and III release ~1-2% of consumed oxygen as superoxide (unavoidable by-product of oxidative phosphorylation). NADPH oxidase (NOX): specialised membrane enzymes that deliberately generate ROS for immune signalling. Xanthine oxidase: in ischaemia-reperfusion. Chronic inflammation: activated macrophages and neutrophils release large amounts.
Endogenous antioxidant defences: Enzymatic: superoxide dismutase (cytoplasmic SOD1, mitochondrial SOD2), catalase, glutathione peroxidase, peroxiredoxins. Non-enzymatic: glutathione (GSH), thioredoxin, vitamins C, E, ubiquinol (reduced CoQ10), uric acid.
The 'mitochondrial theory of ageing' (Harman 1972) holds that accumulation of mitochondrial oxidative damage is central to ageing. But the simplistic version (more antioxidants = more longevity) has been refuted: clinical trials with high doses of antioxidants (vitamin E, beta-carotene) in some cases increased mortality. The modern paradigm (mitohormesis): low doses of ROS are adaptation signals (exercise, caloric restriction), while chronic excess is harmful. The optimal strategy is not to saturate with external antioxidants but to activate endogenous defences (Nrf2 → SOD2, catalase, glutathione) that are finely regulated and don't interfere with physiological signalling.
Scientific sources
- PubMed — Mitohormesis: an emerging concept linking exercise to longevity
- PubMed — Free radicals and antioxidants in normal physiological functions and human disease
- PubMed — Antioxidant supplements for prevention of mortality: a systematic review (Bjelakovic)
- PubMed — Free radicals, antioxidants and aging revisited
Related terms
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