Lack of the AT2R receptor accelerates cardiac senescence and fibrosis in aging mice
Mice lacking the receptor also showed higher inflammation, elevated DNA damage, and a five-month reduction in median lifespan.
Clinical science (London, England : 1979) · Zacarias-Rodrigues LM et al. · Paper published 25 Sep 2026
In a study of young and aged mice, researchers investigated how Type 2 Angiotensin II receptor (AT2R) deficiency affects cardiac aging. The authors compared wild-type mice to AT2R knockout mice at 4 to 5 months and 18 to 21 months of age.
Old knockout mice exhibited impaired systolic and diastolic cardiac function alongside exacerbated fibrosis. Missing AT2R accelerated cardiac senescence, indicated by an early increase in p53, p21, and markers of the senescence-associated secretory phenotype. Aged knockout hearts also showed activation of NF-kB and the NLRP3 inflammasome, accompanied by higher levels of IL-1β and IL-18. In addition, AT2R deficiency caused significant DNA damage even in young animals and reduced median lifespan from 31 months to 26 months.
Why it matters
The findings suggest that AT2R serves as an important mediator of cardioprotection and cellular senescence during aging. Clarifying its role could help researchers understand the biological mechanisms driving age-related cardiac dysfunction.
Caveats
This research was conducted entirely in mice, and these mechanisms may operate differently in humans. In addition, the abstract does not report whether restoring or stimulating the receptor can reverse existing cardiac senescence.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Type 2 Angiotensin II receptor (AT2R) deficiency exacerbates cardiac senescence and fibrosis in aging mice
Zacarias-Rodrigues LM, Parletta AC, Fevereiro MR et al.
Clinical science (London, England : 1979) · 25 Sep 2026 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Notable
- Evidence
- Animals
- Status
- Peer-reviewed
More on Cellular senescence
See allDasatinib and quercetin reduce liver fibrosis in a phase-2 MASH trial
The senolytic combination improved liver fibrosis without disease worsening in nearly half of treated participants while lowering cellular senescence markers.
Nature metabolism · Koning M et al.
A distinct p21-driven macrophage senotype accumulates during aging and liver disease
Researchers identified a p53-p21-Cyclin D2 axis that governs senescent macrophages in mice and human liver cirrhosis and can be cleared with senolytics.
bioRxiv · Torres G et al.
DNA methylation proxies of senescence markers track human disease and mortality
The new blood-based tools estimate senescence gene activity to predict incident diseases, all-cause mortality, and clinical treatment responses.
medRxiv · Simpson DJ et al.
Bispecific T cell engager eliminates senescent cells in mice and nonhuman primates
Monitored by serum transaminase levels, low doses of the drug alleviated age-related pathologies without causing the hepatotoxicity seen at higher doses.
Aging cell · Deng J et al.
A deep learning score for cellular senescence predicts human mortality and disease risk
The proteomic biomarker tracked chronic illness risk in the UK Biobank and shifted following an 18-month multimodal exercise intervention.
Aging cell · Zhao S et al.