As the global population ages, the concept of inflammaging, chronic, sterile, low-grade inflammation associated with aging, is gaining significant attention in both clinical and research settings. While inflammation is typically an acute and protective immune response, inflammaging is distinct. It is a long-lasting process that plays a pivotal role in the onset and progression of age-related diseases such as cardiovascular disease, neurodegeneration, cancer, and metabolic disorders.

This article reviews the cellular and molecular mechanisms underlying inflammaging, its systemic consequences, and evidence-based interventions that can help mitigate its impact.

What Is Inflammaging?

Inflammaging is the term used to describe persistent, systemic inflammation that increases with age, even in the absence of infection or overt disease. Unlike acute inflammation, which is short-lived and resolves after injury or infection, inflammaging is subtle, continuous, and accumulates over years. It contributes to the gradual deterioration of tissues, organs, and immune function (Franceschi et al., 2018; Walker et al., 2022).

Immunosenescence and Immune Imbalance

A hallmark of inflammaging is immunosenescence, the age-related dysregulation of the immune system. In older adults, the innate immune system becomes hyperactive while the adaptive immune system, particularly T and B lymphocytes, experiences a functional decline. This imbalance results in a chronic pro-inflammatory state, driven not by external pathogens but by endogenous signals such as cell debris, metabolic waste, and damaged DNA (Teissier et al., 2022).

Key Biological Drivers of Inflammaging

Cellular senescence is one of the primary contributors to inflammaging. Senescent cells, though no longer dividing, remain metabolically active and release a complex mix of pro-inflammatory cytokines, chemokines, and proteases known as the senescence-associated secretory phenotype (SASP). Key SASP components include interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumour necrosis factor-alpha (TNF-α), all of which perpetuate local and systemic inflammation (Franceschi et al., 2018).

Mitochondrial dysfunction and oxidative stress are also central to inflammaging. With age, mitochondria become less efficient and produce increased levels of reactive oxygen species (ROS), leading to oxidative damage to DNA, lipids, and proteins. This activates inflammatory signalling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the NLRP3 inflammasome.

The accumulation of damage-associated molecular patterns (DAMPs), such as oxidized lipids, fragmented DNA, and misfolded proteins, further stimulates the immune system in a sterile manner. These endogenous signals mimic the effects of microbial infection and provoke an inflammatory response without the presence of a pathogen.

Another important driver is age-related changes in the gut microbiome. Reduced microbial diversity, increased intestinal permeability, and translocation of microbial products such as lipopolysaccharides (LPS) into systemic circulation contribute to chronic immune activation. This gut-derived inflammation is now recognised as a major contributor to systemic inflammaging (Kumar et al., 2025).

The Feedback Loop of Inflammaging

Chronic inflammation sets off a feedback loop where increased oxidative stress damages DNA and mitochondria, leading to accelerated telomere shortening and further cellular senescence. This reinforces SASP secretion and inflammation, creating a self-perpetuating cycle of immune activation and tissue degeneration (Walker et al., 2022).

Molecular Pathways and Biomarkers

Several molecules and signalling pathways are central to the inflammaging process. These include pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, signalling pathways like NF-κB, NLRP3 inflammasome, and JAK/STAT, and oxidative stress markers including ROS, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). At the same time, anti-inflammatory molecules like interleukin-10 (IL-10), sirtuin 1 (SIRT1), and nuclear factor erythroid 2–related factor 2 (Nrf2) are often downregulated with age (Dugan et al., 2023).

Inflammaging and Age-Related Diseases

Inflammaging is a major contributor to the development and progression of numerous chronic diseases commonly associated with aging. These include atherosclerosis, Alzheimer’s disease, type 2 diabetes, osteoporosis, sarcopenia, and various cancers. Persistent inflammation disrupts tissue homeostasis, promotes cellular dysfunction, and accelerates biological aging (Furman et al., 2019; Dugan et al., 2023).

Interventions to Reduce Inflammaging

Evidence points to plant-derived exosomes being able to modulate inflammation and support skin and tissue repair. These nano-sized vesicles carry bioactive molecules such as microRNAs and antioxidants, potentially offering regenerative and anti-inflammatory effects. A range of plant-based exosome formulations is now available for professional use, such as those featured at iD Exo by iD Clinic.

Caloric restriction and intermittent fasting reduce mitochondrial ROS production, suppress NF-κB activity, and enhance cellular repair mechanisms.

Regular physical activity improves antioxidant defense systems, increases levels of enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and lowers systemic inflammation.

Anti-inflammatory dietary patterns, especially the Mediterranean diet, provide bioactive compounds such as resveratrol, curcumin, and quercetin that inhibit inflammatory signaling and support mitochondrial health.

Gut health support through dietary fiber, probiotics, and fermented foods enhances microbial diversity and gut barrier integrity, thereby reducing translocation of LPS and systemic inflammation.

Antioxidant therapies and compounds that maintain telomere length or enhance NAD+ metabolism may further slow the inflammaging process by reducing oxidative stress and cellular damage.

Conclusion

Inflammaging represents a paradigm shift in how aging and age-related diseases are understood. Rather than being seen as an inevitable consequence of age, chronic inflammation is now considered a modifiable driver of disease. Understanding the cellular and molecular mechanisms of inflammaging offers actionable targets for prevention and intervention, particularly in geriatric care, chronic disease management, and healthy aging initiatives.

References

Dugan, B., Conway, J. and Duggal, N.A., 2023. Inflammaging as a Target for Healthy Ageing. Age and Ageing, 52(2), afac328. https://doi.org/10.1093/ageing/afac328

Franceschi, C., Garagnani, P., Parini, P., Giuliani, C. and Santoro, A., 2018. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nature Reviews Endocrinology, 14(10), pp.576-590. https://doi.org/10.1038/s41574-018-0059-4

Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D.W., Fasano, A., Miller, G.W. and Miller, A.H., 2019. Chronic inflammation in the etiology of disease across the life span. Nature Medicine, 25(12), pp.1822–1832. https://doi.org/10.1038/s41591-019-0675-0

Kumar, S., Elmansi, A., Noureldein, M. and Harper, J., 2025. The crosstalk between metabolism and inflammation in aging and longevity. Frontiers in Endocrinology. https://www.frontiersin.org/articles/10.3389/fendo.2025.1734527/abstract

Teissier, T., Boulanger, E. and Cox, L.S., 2022. Interconnections Between Inflammageing and Immunosenescence During Ageing. Cells, 11(3), 359. https://doi.org/10.3390/cells11030359

Walker, K.A., Basisty, N., Wilson, D.M. and Ferrucci, L., 2022. Connecting Aging Biology and Inflammation in the Omics Era. The Journal of Clinical Investigation, 132(14), e158448. https://doi.org/10.1172/JCI158448