Review of macrophage senescence and programmed cell death in atherosclerosis
This review describes how macrophage senescence and programmed cell death contribute to atherosclerosis, shared pathways such as NF-κB, mTOR and p53, and preclinical strategies targeting them. [1]
Automatic summary · not editorially reviewed
The key findings
Senescent macrophages show irreversible cell cycle arrest, mitochondrial dysfunction and a senescence-associated secretory phenotype that worsens inflammation and impairs repair. [1]
Shared pathways such as NF-κB, mTOR and p53 govern both senescence and programmed cell death, though the two differ in nature. [1]
Senolytics, NLRP3 inhibitors, ferroptosis suppressors and autophagy enhancers show promise in preclinical models. [1]
The source at a glance
- Study type / format
- Narrative review (abstract only)
- Population / context
- Macrophages in atherosclerosis, as discussed in a review
- Summary based on
- Study abstract
- Original publication
- July 2, 2026
Senescence and cell death in plaque pathology
The review states that macrophage dysfunction plays a critical role in atherosclerosis. Senescent macrophages show irreversible cell cycle arrest, mitochondrial dysfunction and a senescence-associated secretory phenotype (SASP), which worsens chronic inflammation and impairs tissue repair. Programmed cell death (PCD) pathways — apoptosis, necroptosis, pyroptosis, ferroptosis and autophagy — regulate inflammation and cellular homeostasis, but their dysregulation accelerates arterial pathology. In atherosclerosis, senescent macrophages are described as promoting plaque instability through SASP-driven inflammation and impaired efferocytosis, while necroptosis and pyroptosis are said to worsen necrotic core formation.
Supporting source [1]
Shared NF-κB, mTOR and p53 pathways
The review reports that shared molecular pathways such as NF-κB, mTOR and p53 govern both senescence and PCD. It distinguishes the two: senescence reflects cumulative damage and functional decline, whereas PCD involves regulated, context-dependent cellular demise. The text stresses that context-specific roles of macrophage senescence and PCD need to be delineated.
Supporting source [1]
Preclinical senolytics and pathway-targeting strategies
Emerging strategies targeting these pathways — senolytics, NLRP3 inhibitors, ferroptosis suppressors and autophagy enhancers — are described as showing promise in preclinical models by reducing inflammation, restoring macrophage function and stabilizing plaques. The review names quercetin (a p38 MAPK inhibitor), melatonin (an Nrf2 activator) and senolytic agents as examples of pharmacological interventions with potential to disrupt the senescence-PCD axis. It presents these as a roadmap for dual-targeted therapies and identifies novel biomarkers and therapeutic avenues, not as established human treatments.
Supporting source [1]
How to interpret this
This is an abstract of a review; the full text was not reviewed. The therapeutic strategies are described as promising in preclinical models, not as established human benefits, and associations described are not proven causes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Xu C, Ke C, Zhong YL, Yang XH, Wang MM, Cao Y, Chen J. · europepmc.org · July 2, 2026