How Obesity Fuels Chronic Inflammation in Aging — The Adipaging Connection
A comprehensive review reveals how obesity and aging converge through shared inflammatory biomarkers, accelerating disease risk in the elderly.
Summary
This 2025 narrative review from Greek cardiologists maps the inflammatory biomarkers linking obesity and aging in elderly populations. The authors coin the overlap 'adipaging' — a state where dysfunctional adipose tissue drives chronic low-grade inflammation. Key markers reviewed include CRP, IL-6, leptin, adiponectin, visfatin, TNF-α, fibrinogen, and CXCL-16. CRP levels roughly double with each obesity class increase. Visceral fat accumulates with age while subcutaneous fat shrinks, shifting the body toward a more metabolically harmful state. Epicardial fat transitions from thermogenic-protective to inflammatory, secreting MCP-1, TNF-α, and IL-1β directly into coronary tissue. The review underscores that these biomarkers don't just reflect obesity — they actively drive cardiovascular disease, diabetes, and frailty in older adults, making them potential targets for precision interventions.
Detailed Summary
As global populations age and obesity rates climb — the WHO reports 16% of adults worldwide living with obesity as of 2022 — the intersection of these two conditions is emerging as a defining public health challenge. This 2025 narrative review from cardiologists at multiple Greek academic medical centers synthesizes evidence published between July 2000 and September 2025, cataloguing the inflammatory biomarkers that characterize obese elderly individuals. The authors introduce the term 'adipaging' to describe the convergent pathophysiology of aging and obesity, both of which feature dysfunctional adipose tissue, immune cell dysregulation, and elevated systemic inflammation — a state sometimes called 'inflammaging.'
At the tissue level, aging produces a well-documented redistribution of fat: subcutaneous adipose tissue (SAT) decreases while visceral and pericardial adipose tissue (VAT) increase. This matters because VAT is metabolically harmful, harboring senescent cells that release pro-inflammatory cytokines, whereas SAT is metabolically neutral or even protective. Brown adipose tissue (BAT) declines with age — especially in men — and beige adipose tissue becomes dysfunctional through senescence and chronic inflammation. Particularly notable is epicardial fat: in obesity, it transforms from a thermogenic-protective tissue into an inflammatory depot secreting MCP-1, TNF-α, and IL-1β directly into adjacent myocardium and coronary arteries.
Among the classical biomarkers, C-reactive protein (CRP) shows a progressive, near-doubling with each increase in obesity class, and is further elevated when obesity co-exists with hypertension or type 2 diabetes. Fibrinogen similarly rises with obesity class. IL-6 and CXCL-16 are elevated in overweight and obese elderly compared to normal-weight peers, and positively correlate with anthropometric parameters linked to cardiovascular risk. Leptin, produced primarily from white adipose tissue, is elevated in proportion to fat mass; older adults show additional leptin resistance due to impaired hypothalamic receptor signaling and reduced expression of the leptin transporter LepRa in peripheral monocytes. This resistance means hyperleptinemia in the elderly signals both excess fat and a blunted homeostatic response.
Visfatin, secreted from VAT by both adipocytes and infiltrating macrophages, is elevated in obesity but shows an inverse relationship with age: multiple studies demonstrate a steady decrease in plasma visfatin levels for each year of age in obese non-diabetic subjects. This age-related decline complicates its utility as a biomarker in older populations. Adiponectin presents the inverse pattern — it is anti-inflammatory and insulin-sensitizing, yet is paradoxically reduced in obesity despite rising fat mass, and its levels are modulated by sex and adipose depot. The shift from anti-inflammatory B-1 cells to pro-inflammatory B-2 cells in adipose tissue, driven by both obesity and aging, further amplifies cytokine production including IL-6 and TNF-α, perpetuating a self-reinforcing inflammatory cycle linked to insulin resistance and atherosclerosis.
The review highlights important clinical nuances: sarcopenic obesity — loss of muscle mass combined with excess fat — affects approximately 10% of older adults and is poorly captured by BMI alone. The 'obesity paradox,' wherein overweight individuals with chronic illness sometimes show better short-term survival than normal-weight counterparts, is partly explained by fat distribution differences and cachexia effects. The authors argue that clarifying whether these biomarkers operate complementarily or independently in aging versus obesity could unlock targeted therapeutic strategies. They call for further research specifically in elderly cohorts, noting that most biomarker data come from mixed-age or middle-aged adult populations.
Key Findings
- CRP levels nearly double with each increase in obesity class compared to normal weight individuals, and are further elevated when obesity co-exists with hypertension or type 2 diabetes
- Subcutaneous adipose tissue decreases with age while visceral and pericardial VAT increase, shifting the metabolic risk profile of elderly individuals toward greater inflammation
- Sarcopenic obesity — excess fat combined with muscle loss — affects approximately 10% of older adults and is associated with worse quality of life and clinical outcomes
- Visfatin plasma levels show a steady inverse relationship with age in obese non-diabetic subjects, decreasing progressively for each year of age across multiple independent studies
- Epicardial adipose tissue transitions from thermogenic-protective to inflammatory in obesity, secreting MCP-1, TNF-α, and IL-1β directly into myocardium and coronary arteries
- Obesity drives a shift from anti-inflammatory B-1 cells to pro-inflammatory B-2 cells in adipose tissue, amplifying IL-6 and TNF-α production and perpetuating insulin resistance and atherosclerosis
- WHO data (2022): 16% of adults globally — 1 in 8 people — are living with obesity, with the elderly projected to exceed 2.2 billion individuals by the late 2070s, compounding the public health burden
Methodology
This is a narrative review (not a systematic review or meta-analysis) of literature published from July 2000 to September 2025, identified through PubMed and Embase using MeSH terms and Boolean operators. Search terms included 'obesity,' 'inflammatory biomarkers,' 'aging,' 'immune system,' 'inflammatory aging,' and 'elderly population,' with reference lists of included articles manually reviewed. No formal PRISMA protocol, risk-of-bias assessment, or quantitative pooling of effect sizes was performed, which is consistent with the narrative review design but limits the strength of conclusions.
Study Limitations
As a narrative rather than systematic review, selection bias in included studies cannot be excluded, and no formal quality appraisal or meta-analytic synthesis was conducted. Most underlying studies reviewed were conducted in mixed-age or middle-aged adult populations, limiting direct extrapolation to the elderly; the authors explicitly call for more biomarker research specifically in elderly cohorts. No external funding was received, and no conflicts of interest were declared by the authors.
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