Omega-3 fatty acids as modulators of advanced glycation end products in aging: mechanistic pathways and clinical implications - a narrative review
Abstract
Background: Aging is characterised by the progressive accumulation of advanced glycation end products (AGEs), formed through non-enzymatic glycation reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs contribute to tissue damage through irreversible protein cross-linking and receptor-mediated inflammatory signalling via the receptor for AGEs (RAGE). Elderly individuals are disproportionately affected due to cumulative oxidative stress, chronic low-grade inflammation (inflammaging), impaired renal and enzymatic clearance, and prolonged exposure to dietary AGEs. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may modulate these pathways through anti-inflammatory, antioxidant, and metabolic mechanisms.
Objectives: To synthesise available preclinical, in vitro, and clinical evidence on the mechanistic and therapeutic relationships between omega-3 PUFA supplementation and AGE formation, accumulation, and signalling, and to evaluate the effects of omega-3 supplementation on key age-related clinical outcomes in elderly populations, including cardiometabolic health, cognitive function, mental health, functional capacity, and quality of life.
Methods: A narrative review was conducted using searches of PubMed, Scopus, and Web of Science. Eligible study designs included in vitro experiments, animal models, randomised controlled trials (RCTs), observational studies, and systematic reviews…
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