MedCommOct 24, 2026

Blocking Leptin Reduces Age-Related Inflammation in Blood Vessel and Immune Cells

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 25, 2026

Abstract

In healthy individuals, leptin levels were higher in those with hs-CRP ≥ 3 mg/dL compared to those below this threshold.

Leptin contributes to chronic low-grade inflammation associated with obesity and may also play a role in age-related inflammation.
Blocking leptin receptor binding in endothelial cells enhanced cellular senescence, while neutralizing leptin suppressed inflammatory markers.
In macrophages and endothelial cells, leptin blockade reduced inflammation induced by hyperglycemia and lipopolysaccharide exposure.
Leptin neutralization showed varied effects in T cells, reducing inflammation in conventional T cells but not affecting regulatory T cells.
Leptin levels correlated positively with inflammatory markers IL-6 and hs-CRP in healthy individuals, and with hs-CRP and IL-8 in those with Type 2 diabetes.

Simplified

Leptin, a proinflammatory adipokine, contributes to the chronic low-grade inflammation seen in obesity, but its role in age-related inflammation, that is inflammaging, has been poorly studied. We thus tested the effect of blocking leptin receptor (LEP-R) binding in five models of inflammaging, that is replicative senescent endothelial cells, hyperglycemia-treated macrophages or endothelial cells, lipopolysaccharide (LPS)-exposed macrophages, and TCR-stimulated CD4+ T cells. In endothelial cells, leptin enhanced senescence, while leptin neutralization suppressed the senescence-associated secretory phenotype, two effects mediated in part by the mTOR pathway. In both macrophages and endothelial cells, leptin blockade blunted hyperglycemia-induced inflammation, while in macrophages, it also suppressed the LPS-induced senescent and proinflammatory phenotype. In T cells, leptin neutralization produced divergent effects, attenuating the expression of inflammatory and senescence markers in conventional T cells but not in regulatory T cells. To assess translational relevance, we measured leptin and inflammaging markers in plasma samples from two independent cohorts, one of healthy individuals (n = 121) and another of people with Type 2 diabetes (n = 93). In healthy subjects, leptin levels were higher in people with hs-CRP ≥ 3 mg/dL compared with those below such threshold, also after adjustment for BMI. Leptin levels showed BMI-adjusted positive correlations with IL-6 and hs-CRP in healthy individuals and with hs-CRP and IL-8 in people with diabetes. These findings suggest that leptin might fuel inflammaging and that its neutralization exerts anti-inflammatory effects across multiple, related models.

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Blocking Leptin Reduces Age-Related Inflammation in Blood Vessel and Immune Cells

Abstract

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