Can Agri-Food By-Products Modulate Inflammaging? A Critical Review of Mechanistic Evidence

Agri-food by-products are increasingly valued as sources of bioactive compounds, but whether their anti-inflammatory activity is relevant to inflammaging remains uncertain. This review evaluated mechanistic evidence linking agri-food by-product-derived preparations to molecular and cellular processes in age-associated chronic inflammation. A structured literature search identified studies addressing nuclear factor kappa B (NF-κB) and pro-inflammatory cytokine signaling, NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, and redox–inflammation crosstalk, while additional pathways were considered within the inflammaging framework. Thirty studies met predefined criteria for mechanistic assessment. Ten studies provided anti-inflammatory or immunomodulatory evidence (Level 1), whereas 20 assessed mechanisms relevant to inflammaging (Level 2). None fulfilled criteria for aging- or senescence-specific evidence (Level 3) or human aging evidence (Level 4). Across categories, polyphenol-rich preparations predominated, although polysaccharides, proteins and peptides, lipid-associated constituents, and other bioactive classes were represented. Evidence supports modulation of NF-κB, inflammatory cytokines, NLRP3-related signaling, and redox-sensitive pathways; however, most studies used acute inflammatory challenges or disease-specific models. Dose, chemical composition, processing, bioavailability, gut microbial transformation, and context-dependent immunomodulation influence responses. Thus, agri-food by-product-derived preparations show mechanistic relevance to inflammaging pathways, but direct anti-inflammaging effects remain to be demonstrated in aging-specific experimental systems and older human populations.