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Hedi Raizer

Journal 6 min read

What is inflammaging?

Inflammaging is the chronic, low-grade, sterile inflammation that accompanies ageing. This page defines the term, outlines the pathways involved, and summarises what the current research literature reports.

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What is inflammaging?

Inflammaging is the formal term for chronic, low-grade, systemic inflammation that develops with advancing age in the absence of an overt pathogen. It is not a disease and has no agreed diagnostic criteria; it is a descriptive biological construct used to organise observations of persistently elevated circulating inflammatory mediators in older populations. Synonyms in the literature include "chronic low-grade inflammation" and "age-related inflammation." The term is not associated with a sequence, formula, or molecular weight, because it describes a physiological state rather than a single molecule.

The mechanistic work centres on the innate immune system and its cytokine networks — principally interleukin-6 (IL-6), tumour necrosis factor, and C-reactive protein — together with the senescence-associated secretory phenotype (SASP) and damage-associated molecular patterns (DAMPs) released by stressed or dying cells [3][4][10].

Research Studies

Inflammaging and sarcopenia: mitochondrial dysfunction and cellular senescence

A review of biomarkers and early mechanisms of sarcopenia reported that the condition results from complex interactions among mitochondrial dysfunction, chronic low-grade inflammation (inflammaging), cellular senescence, neuromuscular junction degeneration, and anabolic resistance [3]. The review described sarcopenia as a progressive age-related skeletal muscle disorder characterised by loss of muscle mass, strength, and physical performance, leading to frailty, disability, and increased mortality. The authors noted that the underlying biological mechanisms remain incompletely understood, which limits the development of early diagnostic strategies and targeted therapies [3].

Myokines and the muscle–brain axis in ageing

A narrative review synthesised mechanistic and translational evidence on how skeletal muscle communicates with the ageing brain through myokines and exerkines, including irisin/FNDC5, brain-derived neurotrophic factor (BDNF), IL-6, insulin-like growth factor-1 (IGF-1), cathepsin B, and growth differentiation factor-15 (GDF-15) [2]. The review reported that sarcopenia and cognitive decline frequently co-occur in older adults and that growing evidence indicates these conditions share a common biological substrate centred on the muscle–brain axis. It further described how progressive sarcopenia disrupts this signalling to accelerate cognitive impairment [2].

Inflammaging and glucose metabolism in elderly subjects

A registered clinical study characterised glucose metabolism and inflammaging in elderly subjects to determine the extent to which each factor affects muscle mass and function and contributes to age-related muscle wasting [6]. The investigators planned to correlate patterns of insulin secretion and sensitivity with muscle quality and quantity in diabetic and non-diabetic individuals aged 70 years and older. By comparing healthy, sarcopenic, diabetic, and diabetic/sarcopenic groups, they expected to identify an oxidative/inflammatory signature — for example, circulating interleukins and myokines, and plasma antioxidant capacity — specific to the sarcopenic phenotype and related to muscle insulin resistance [6].

Inflammaging in the heart–brain–bone axis

A review of lipid-soluble nutrients — long-chain omega-3 fatty acids, vitamin D3, and vitamin K2 — described a proposed "Heart–Brain–Bone" axis linking cardiovascular disease, neurocognitive decline, and osteoporotic bone loss [1]. The authors reported that mechanistic data indicate these systems are coupled through shared regulators of calcium trafficking, inflammation resolution, vascular integrity, and inflammaging. They explicitly framed the axis as an integrative conceptual framework that organises evidence drawn from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability [1].

Nutritional micronutrients and inflammaging in cardiovascular risk

A registered clinical study examined the relationship between fruit and vegetable consumption and reduced cardiac risk, noting that this relationship could be mediated via improvements in blood pressure, platelet function, and vascular reactivity [5]. The study reported that certain vitamins and polyphenols found in fruits and vegetables have antioxidant and anti-inflammatory effects and play a major role in the function of immune cells. It also cited previous findings on omega-3 fatty acids and their involvement in the inflammatory response and cardiovascular system in humans [5].

Alpha-ketoglutarate and surgical stress in older patients

A registered clinical trial is investigating alpha-ketoglutarate in the context of coronary artery bypass grafting (CABG), a procedure performed in approximately 400,000 patients in the United States each year [4]. The study background describes CABG as invoking a massive surgical stress response, with systemic epinephrine increasing 33-fold and norepinephrine increasing 3-fold. Local tissue injury results in sterile inflammation and the release of DAMPs, which activate neutrophils and trigger a cascade of cytokines, complement, and coagulation changes. Activation of nociceptors produces a neurometabolic response involving the sympathetic nervous system and the hypothalamus–pituitary axis [4].

Inflammaging in vascular, ovarian, and skin ageing

Several reference sources place inflammaging within broader models of organ-specific ageing. One review proposed that chronic, largely mutation-independent overactivation of the DNA damage response acts as an upstream integrating node in ageing, dysregulating tumour-suppressor networks [7]. Another described intracranial aneurysms as a manifestation of premature vascular ageing driven by cellular senescence, chronic inflammation, and haemodynamic stress [8]. A third outlined ovarian ageing as contributing to systemic ageing via an ovarian–systemic axis, with intrinsic ovarian defects triggering SASP-related inflammaging and fibrosis [10]. A fourth described skin ageing as modulated by intrinsic genetic programming and extrinsic environmental stressors, with molecular signatures including telomere attrition, mitochondrial dysfunction, and epigenetic drift [9]. These sources are cited for context; they are not the primary evidence base for the definition above.

Comparison of study populations and reported mechanisms

StudyPopulation or modelReported mechanism or focus
Biomarkers of sarcopenia [3]Older adults (review)Mitochondrial dysfunction, inflammaging, cellular senescence, neuromuscular degeneration, anabolic resistance
Myokines and muscle–brain axis [2]Older adults (narrative review)Irisin/FNDC5, BDNF, IL-6, IGF-1, cathepsin B, GDF-15
Glucose metabolism and inflammaging [6]Elderly subjects ≥70 years, diabetic and non-diabeticInsulin secretion/sensitivity, oxidative/inflammatory signature, muscle insulin resistance
Heart–Brain–Bone axis [1]Conceptual framework (review)Calcium trafficking, inflammation resolution, vascular integrity, inflammaging
Cardiovascular and inflammaging [5]Human study (registered)Fruit and vegetable intake, blood pressure, platelet function, vascular reactivity, omega-3
Alpha-ketoglutarate and CABG [4]Older surgical patients (registered trial)Surgical stress response, DAMPs, neutrophil activation, cytokine cascade

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