Skin ageing and damage resulting from RCS/AGEs-mediated carbonyl stress and associated intervention strategies

Reactive carbonyl species (RCS) derived from glycoxidation, mainly α-dicarbonyl compounds (α-DCs), can induce covalent modifications in biological macromolecules, particularly proteins and DNA, leading to formation of advanced glycation end products (AGEs). The excessive accumulation of RCS and AGEs contributes to a pathophysiological condition known as carbonyl stress. Carbonyl stress varies with age, diet, and environmental factors. It is further aggravated by oxidative stress and health conditions like hyperglycemia and renal dysfunction. Increasing evidence indicates that RCS/AGEs-mediated carbonyl stress is involved in disruption of cellular homeostasis and damage of physiological functions of the skin, clinically presenting as chronic inflammation, yellowish discoloration, accelerated aging, and other dermatological abnormalities. Consequently, targeted modulation of the RCS/AGEs axis represents a promising therapeutic strategy for cutaneous health preservation. This review provides a first systematic discussion on the role of RCS/AGEs-induced carbonyl stress in skin ageing and damage. Furthermore, the key intervention strategies against carbonyl stress are summarized, including (i) inhibition of RCS/AGE formation and exogenous intake; (ii) scavenging of preformed RCS/AGEs; (iii) blockade of AGE-receptor interactions. Notably, interventions based on dietary bioactives hold promise for designing personalized diets and developing functional foods to mitigate carbonyl stress-associated skin ageing and damage.