Chronic low-grade inflammation, termed inflammaging, is now treated as a central driver of cardiovascular disease, neurodegeneration, metabolic syndrome, and frailty. This review argues that diet sits on both sides of that process. Certain food-derived molecules, including advanced glycation end products, oxidised lipids, industrial trans fats, and gut-microbial metabolites such as TMAO, behave like damage signals and switch on the NF-kappa-B inflammatory program. A second group of food compounds, including polyphenols, sulforaphane, omega-3 fatty acids, carotenoids, and the microelements zinc, selenium, and magnesium, push in the opposite direction, mostly by suppressing NF-kappa-B or activating the KEAP1/NRF2 cytoprotective system. The authors synthesise cell, animal, and human evidence for roughly twenty compounds, then concede the central problem: human evidence is almost entirely limited to short-term movement in inflammatory blood markers, not to demonstrated extension of lifespan or reduction in hard clinical endpoints.
The idea that aging is partly an inflammatory disease is roughly twenty-five years old. Claudio Franceschi, a co-author here, coined the term inflammaging in 2000 to describe the slow, sterile, chronic immune activation that accumulates across decades without any infection to explain it. What began as an immunologist’s observation has since been folded into the mainstream framework of aging biology, and this review is essentially an argument about where a meaningful share of that inflammatory signal comes from: food.
The big idea is that the immune system does not distinguish cleanly between a pathogen and a molecule that merely looks damaged. Cooking chemistry produces molecules that look damaged. Frying, baking, and grilling generate advanced glycation end products, which bind the RAGE receptor and drive vascular stiffening. Reheated and rancid fats generate oxysterols and reactive aldehydes. Industrial trans fats activate NF-kappa-B directly in the cells lining blood vessels. Gut bacteria fed on red meat and eggs produce TMAO, which activates macrophages and promotes clotting. The authors group these under a single label, dietary damage-associated molecular patterns, and the framing is useful: these are not toxins in the classical dose-response sense but decoy danger signals that keep the innate immune system idling above zero for decades.
The counter-argument occupies most of the paper. Quercetin, EGCG from green tea, curcumin, and resveratrol suppress the same NF-kappa-B and NLRP3 machinery. Sulforaphane from broccoli, hydroxytyrosol from olive oil, and boswellic acids from frankincense work through a different route, the KEAP1/NRF2 pathway, switching on a defensive gene program that includes heat shock proteins and antioxidant enzymes. Omega-3 fatty acids shift the body’s lipid signalling away from inflammatory eicosanoids toward resolvins and protectins, molecules that actively terminate inflammation rather than merely blocking it.
The honest part of the review is its ending. Nearly all of the mechanistic work was done in cell culture or rodents at concentrations humans cannot reach by eating. Curcumin, quercetin, and resveratrol are poorly absorbed, reaching blood levels orders of magnitude below what the laboratory experiments required. Human trials mostly report changes in blood markers such as CRP and IL-6, not survival. And the two largest omega-3 cardiovascular trials disagreed with each other despite similar doses. The conclusion the authors reach, correctly, is that the strongest human evidence is not for any single compound but for whole dietary patterns.
Insights
What the review does support is that dietary pattern beats dietary molecule. The human evidence that survives scrutiny comes from Mediterranean and DASH-style eating.
The only intervention here with a hard outcome is high-dose purified EPA at 4 g/day in the REDUCE-IT trial, which cut major cardiac events by about a quarter in high-risk patients on statins. That is a genuine clinical effect, but it is a prescription drug dose in sick people, not a longevity strategy. A near-identical trial using a mixed EPA/DHA formulation found nothing.
Practical reading: cut fried, grilled, and reheated fats, refined sugar, industrial trans fats, and heavy processed meat, since the pro-inflammatory side of this ledger is better established than the protective side. Eat oily fish, vegetables, legumes, nuts, and olive oil.
Context and Source
Paywalled Paper: Dietary bioactive compounds and inflammaging: Pro-inflammatory triggers and geroprotective countermeasures
Authors: Alexey Moskalev, Oksana Veselova, Vittorio Calabrese, Luay Rashan, Claudio Franceschi
Institutions: Petrovsky National Research Center of Surgery, Institute of Biology of Aging and Healthy Longevity Medicine, Moscow, Russian Federation (lead); University of Catania, Italy; Dhofar University, Salalah, Oman; Lobachevsky State University, Nizhny Novgorod, Russian Federation
Country of origin: Russian Federation, with Italian and Omani collaboration
Journal: Ageing Research Reviews, volume 121 (2026)
Article type: Review article.