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Hedi Raizer

Journal 6 min read

What does the research say about inflammaging?

Inflammaging is the chronic, low-grade, systemic inflammation that accompanies ageing. This page summarises what the research literature reports about its mechanisms, its measurement, and its proposed links to muscle, br

peptides-pro Editorial

Inflammaging is the term used in the research literature for chronic, low-grade, systemic inflammation that develops with advancing age. It is not a disease and it is not a clinical diagnosis; it is a descriptive concept used to organise observations of persistently elevated circulating inflammatory mediators in older populations, in the absence of overt infection or autoimmune disease. The literature does not assign it a sequence, a molecular formula or a molecular weight, because it is not a single molecule — it is a state, defined operationally by patterns of cytokines, acute-phase proteins and oxidative markers measured in blood or tissue.

The mechanistic work centres on a small set of interacting pathways: nuclear factor kappa-B (NF-κB) signalling, the NLRP3 inflammasome, and the senescence-associated secretory phenotype (SASP) that senescent cells use to release interleukins and other mediators into their surroundings [3][8][10].

Research Studies

Inflammaging and sarcopenia: the muscle axis

A 2025 review of biomarkers and early mechanisms in sarcopenia reports that the condition — progressive loss of muscle mass, strength and physical performance — is not explained by any single process. The authors describe it as arising from interactions among mitochondrial dysfunction, chronic low-grade inflammation (inflammaging), cellular senescence, neuromuscular junction degeneration and anabolic resistance [3]. In that framing, inflammaging is one contributor among several, not the sole driver.

Myokines and the muscle-brain axis

A narrative review of myokines as mediators of a muscle-brain axis reports that sarcopenia and cognitive decline frequently co-occur in older adults and appear to share a biological substrate. The review synthesises evidence on signalling molecules released by skeletal muscle — including irisin/FNDC5, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), cathepsin B and growth differentiation factor-15 (GDF-15) — and proposes that progressive sarcopenia disrupts this signalling in ways that accelerate cognitive impairment [2]. IL-6 appears in both the muscle and inflammation literature, which is one reason the two research areas overlap.

Inflammaging and the heart-brain-bone framework

A 2025 review proposes a "Heart-Brain-Bone" axis linking cardiovascular disease, neurocognitive decline and osteoporotic bone loss through shared regulators of calcium trafficking, inflammation resolution, vascular integrity and inflammaging [1]. The authors are explicit that this should be read as an integrative conceptual framework organising evidence from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability [1].

Inflammaging and vascular ageing: intracranial aneurysms

A review of intracranial aneurysms as a manifestation of premature vascular ageing reports that chronological age is a major risk factor for aneurysm formation, growth and rupture, and that vascular ageing beyond chronology appears driven by cellular senescence, chronic inflammation and haemodynamic stress [8]. In this model, inflammaging is positioned as part of a degenerative process in the vessel wall rather than as a systemic marker alone.

Inflammaging and ovarian ageing

A review of ovarian ageing and systemic health reports that intrinsic ovarian defects — genomic instability, epigenetic shifts, and mitochondrial and proteostasis damage — may trigger SASP-related inflammaging and fibrosis, and proposes an ovarian-systemic axis through which this could contribute to ageing in other tissues [10]. This is a proposed mechanism; the review does not report an intervention trial.

Inflammaging and skin ageing

A review of skin ageing reports that the process is multifactorial and dynamically regulated, with chronological skin ageing dominated by molecular signatures including telomere attrition, mitochondrial dysfunction and epigenetic drift [9]. Inflammaging appears in that literature as one component of a broader molecular landscape rather than as an isolated target.

Inflammaging and the DNA damage response

A hypothesis paper proposes that chronic, largely mutation-independent overactivation of the DNA damage response acts as an upstream integrating node in ageing, dysregulating tumour-suppressor networks [7]. This is presented as a hypothesis, not as an established causal chain, and it does not report inflammaging measurements directly.

Measuring inflammaging in older populations

Two registered clinical studies illustrate how the concept is operationalised. One characterises glucose metabolism and inflammaging in adults aged 70 and over, correlating insulin secretion and sensitivity with muscle quality and quantity across healthy, sarcopenic, diabetic and diabetic-sarcopenic groups, and expects to identify an oxidative/inflammatory signature — circulating interleukins and myokines, plasma antioxidant capacity — specific to the sarcopenic phenotype and related to muscle insulin resistance [6]. The other examines cardiovascular risk and inflammaging in the context of fruit, vegetable and omega-3 intake, noting prior evidence that certain vitamins and polyphenols have antioxidant and anti-inflammatory effects and influence immune cell function [5].

Inflammaging and surgical stress

A registered trial in patients undergoing coronary artery bypass grafting describes the surgical stress response in mechanistic terms: systemic epinephrine rising 33-fold and norepinephrine 3-fold, local tissue injury producing sterile inflammation and release of damage-associated molecular patterns, and downstream activation of neutrophils, cytokines, complement and coagulation [4]. This is acute inflammation rather than inflammaging, but the trial is relevant because it examines an older surgical population in which baseline inflammatory state is a variable of interest.

Comparison of study designs

StudyDesignPopulation or modelInflammaging-related focus
NCT02426073 [6]Observational characterisationAdults ≥70 years, diabetic and non-diabeticInsulin secretion/sensitivity vs muscle quality; oxidative/inflammatory signature
NCT04763291 [5]Nutritional intervention studyAdults assessed for cardiovascular riskFruit, vegetable and omega-3 intake; immune cell function
NCT07031128 [4]Surgical trialOlder patients undergoing CABGAcute surgical stress response; cytokine and DAMPs cascade
Review [3]Narrative reviewSarcopenia literatureMitochondrial dysfunction, inflammaging, senescence, NMJ degeneration
Review [2]Narrative reviewMuscle-brain axis literatureMyokines and exerkines linking sarcopenia to cognitive decline

Where the evidence is limited

Several of the sources above are narrative reviews or hypothesis papers rather than controlled trials, and the mechanistic claims they contain are drawn largely from cellular and animal work. The Heart-Brain-Bone framework is explicitly described by its authors as conceptual rather than validated [1]. The DNA damage response model is presented as a hypothesis [7]. The clinical studies listed are registered protocols; their results are not reported in the evidence summarised here [4][5][6].

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