Food bioactives as modulators of autophagy and mitophagy ininflammaging and healthy aging

چکیده

Aging is associated with progressive cellular dysfunction, mitochondrial damage, impaired proteostasis, and chronic low-grade inflammation, commonly referred to as inflammaging. Autophagy and mitophagy, the cellular quality control mechanisms responsible for degrading dysfunctional proteins and mitochondria, decline with age and contribute to age-related pathologiesFood-derived bioactive compounds modulate these processes through key signaling pathways, including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), and the PTEN-induced kinase 1 (PINK1)/Parkin pathway. This mini review synthesizes current mechanistic, preclinical, and clinical evidence on how specific bioactives—resveratrol, curcumin, quercetin, spermidine, urolithin A, carotenoids, omega-3 fatty acids, sulforaphane, and microbiota-derived metabolites— may influence pathways relevant to healthy aging, including autophagy and mitophagy, based primarily on mechanistic and preclinical evidence. Particular attention is given to bioavailability, microbiome-dependent metabolism, biomarker limitations, and functional food development, where translation from mechanistic findings to clinically validated applications remains incomplete. Overall, dietary bioactives represent a scientifically grounded but clinically developing approach for supporting cellular quality control and reducing inflammatory mechanisms associated with biological aging.

Novelty of the study: This review provides an integrated mechanistic framework linking food-derived bioactive compounds with autophagy, mitophagy, mitochondrial quality control, and inflammaging. Rather than presenting bioactives as general antioxidants or anti-inflammatory agents, it emphasizes their effects on specific regulatory pathways—AMPK, mTOR, SIRT1, Nrf2, NF-κB, and PINK1/Parkin— and their reported capacity to influence cellular quality-control pathways that decline with age. The review further distinguishes compounds by the strength of evidence across mechanistic, preclinical, and clinical levels. It also highlights microbiota-derived metabolites and the translation of functional foods as priority areas that the field must advance before dietary bioactives can be responsibly recommended for healthy aging applications.

Keywords: autophagy; mitophagy; inflammaging; healthy aging; food bioactives; AMPK; mTOR; SIRT1; Nrf2; PINK1/Parkin; resveratrol; curcumin; spermidine; urolithin A; functional food