Vascular ageing triad in atherosclerosis: senescence, inflammaging and epigenetics
This abstract reviews how biological ageing of the artery wall — cellular senescence, systemic inflammaging and epigenetic dysregulation — may amplify atherosclerosis alongside lipids, and weighs senolytic and senomorphic strategies. [1]
Automatic summary · not editorially reviewed
The key findings
The review proposes that intrinsic biological ageing of the vascular wall is a potent amplifier and primary driver of atherogenesis, acting together with circulating lipids. [1]
Mechanical and metabolic stressors are said to push endothelial and vascular smooth muscle cells into a usually stable senescent state, triggering the senescence-associated secretory phenotype. [1]
Murine models are said to suggest highly sexually dimorphic plaque immunophenotypes, and nanotechnology strategies are described as preclinical proof of concept. [1]
The source at a glance
- Study type / format
- Narrative review of literature from 2020 onwards plus foundational studies (abstract only)
- Population / context
- Not specified in the abstract; the review discusses older populations and murine models.
- Summary based on
- Study abstract
- Original publication
- October 16, 2026
Review asks why lipids alone miss arterial ageing
Atherosclerotic cardiovascular disease remains a leading global cause of cardiovascular death, yet the authors say traditional lipid-focused models do not explain the residual cardiovascular risk seen in older populations. This review, drawing on literature from 2020 onwards plus foundational studies, examines the 'geroscience hypothesis': that intrinsic biological ageing of the vascular wall is a potent amplifier and primary driver of atherogenesis, acting together with circulating lipids. The authors describe a pathogenic triad of cellular senescence, systemic inflammaging and epigenetic dysregulation.
Supporting source [1]
Senescent vessel cells, exhausted macrophages and trained immunity
At the cellular level, the review states that mechanical and metabolic stressors push endothelial and vascular smooth muscle cells into a usually stable senescent state, triggering the senescence-associated secretory phenotype. Immunologically, it links atherosclerosis in older people to metabolically exhausted macrophages, clonal haematopoiesis of indeterminate potential and cytotoxic memory T cells. It further proposes that metabolic stressors such as hyperglycaemia cause long-lasting changes to the chromatin landscape of haematopoietic stem cells, establishing 'trained immunity' and a persistent pro-inflammatory metabolic memory. These processes are described as governed by an altered epigenetic landscape, including loss of protective sirtuins and aberrant RNA methylation, which the authors say accelerate biological clocks such as GrimAge.
Supporting source [1]
Sex differences and preclinical senotherapeutic strategies
Clinically, the authors state that vascular ageing trajectories are highly sexually dimorphic and strongly influenced by midlife metabolic clustering and endocrine shifts, and that murine models suggest highly sexually dimorphic plaque immunophenotypes. They then evaluate the translational frontier of precision senotherapeutics, contrasting senomorphics — such as repurposed metformin and natural polyphenols that suppress the senescence-associated secretory phenotype — with targeted senolytics. Emerging nanotechnology, including in vivo CAR-T lipid nanoparticles and responsive peptide nanoassemblies, is described as offering preclinical proof-of-concept strategies to selectively clear senescent cells without systemic toxicity. The authors conclude that mitigating atherosclerotic cardiovascular disease requires moving beyond lipid management to integratively target the biological clock of the artery.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is a narrative review synthesising other studies, not new human data. The murine and nanotechnology findings are preclinical; no human lifespan or outcome benefit is shown. Associations described are not proven causes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Dabravolski SA, Borodko DD, Antonov SA, Lukina SS, Poletaev AA, Sukhorukov VN. · europepmc.org · October 16, 2026