Proposed framework: mechanometabolic endothelial senescence in cardiometabolic vascular disease
This Review proposes mechanometabolic endothelial senescence as a testable, context-dependent amplifier of cardiometabolic vascular disease and vascular ageing, not a universal primary cause; supporting evidence is strongest in preclinical or mixed translational studies. [1]
Automatic summary · not editorially reviewed
The key findings
The Review proposes mechanometabolic endothelial senescence as a context-dependent disease amplifier and testable translational model, not a universal primary cause. [1]
Evidence from human tissue, clinical studies, animal models, flow systems and cell experiments indicates that haemodynamic and metabolic stresses can converge on senescence-related signalling. [1]
Sex-disaggregated mechanistic data remain sparse, although biological sex modifies the framework. [1]
The source at a glance
- Study type / format
- Review (abstract)
- Population / context
- Human vascular tissue, clinical vascular-function study participants, animal models, flow-controlled systems and endothelial cells, as described in the Review
- Summary based on
- Study abstract
- Original publication
- October 8, 2026
Umbrella term and proposed framework
The Review uses cardiometabolic vascular disease as an operational umbrella for vascular injury from interacting metabolic, renal and cardiovascular stress, not as a standardised diagnosis. It examines mechanometabolic endothelial senescence as a framework linking local haemodynamic vulnerability with systemic cardiometabolic load. The authors conclude it is best viewed as a context-dependent disease amplifier and testable translational model, not a universal primary cause.
Supporting source [1]
Converging signals and sparse sex-specific data
Evidence from human vascular tissue, clinical vascular-function studies, animal models, flow-controlled systems and endothelial-cell experiments indicates that low or oscillatory shear, matrix stiffness, hyperglycaemia, dyslipidaemia, uraemic and hepatic stress, inflammation and oxidative injury can converge on DNA-damage responses, p53/p21 and p16/pRB signalling, NAD⁺-sirtuin decline, mitochondrial dysfunction, metabolic rewiring and chromatin regulation. Biological sex modifies this framework: endothelial function declines across the menopause transition, and direct human arterial evidence suggests senescence-associated endothelial dysfunction may differ between women and men, but sex-disaggregated mechanistic data remain sparse.
Supporting source [1]
Functional anchors and staged validation proposal
Clinically, flow-mediated dilatation, carotid-femoral pulse-wave velocity, coronary flow reserve and the index of microcirculatory resistance provide compartment-specific functional anchors, but none is a direct senescence assay. Evidence in heart failure with preserved ejection fraction, chronic kidney disease and metabolic dysfunction-associated steatotic liver disease remains heterogeneous and is strongest in preclinical or mixed translational studies. The authors therefore propose a staged validation strategy combining endothelial identity, convergent senescence markers, circulating-cell or extracellular-vesicle measures, vascular function and organ-specific outcomes.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The framework is proposed, not validated. Evidence is strongest in preclinical or mixed translational studies, and no listed vascular measure is a direct senescence assay.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Lanlan L, Fan G, Ran Z, Xiaoqing Z, Yitong C, Jingjing Z, Lei L, Jianhua F. · europepmc.org · October 8, 2026