Work

Age-related cardiac dysfunction is not associated with shorter telomere length in laboratory rats

Year: 2026

Type: article

Abstract: Introduction Ageing is an independent risk factor for cardiovascular disease (CVD). Preclinical models of ageing are needed to better understand human diseases. Telomere shortening is a critical process in cellular ageing and senescence. In humans, it is well-established that telomere shortening in circulating leukocytes is associated with CVD, however, whether this applies to common preclinical models remains disputable. We investigated leukocyte telomere length (LTL), cardiac telomere length (CTL), and age-related cardiac remodeling and functional decline in commonly used laboratory rats. Methods Sprague-Dawley rats ( n = 51) were euthanized at 3, 9, 16, or 24 months (mo), respectively. Cardiac function was assessed by echocardiography. Relative telomere length, mRNA levels of telomerase and signature genes involved in inflammation and fibrosis were quantified in circulating leukocytes and left ventricular tissue by quantitative or digital droplet PCR (qPCR or ddPCR, respectively). Results Rats with increasing chronological age (16/24 months compared to 9 months) exhibited cardiac hypertrophy and diastolic dysfunction, as evidenced by increased septal and posterior wall thickness, and elevated E/e’ ratio, and increased cardiac expression of central inflammatory ( Il6 ) and fibrotic ( Ctgf ) genes. Relative LTL and CTL remained unchanged across chronological age groups (LTL: 9 months 1.000 vs. 16 months 0.939 vs. 24 months 1.120, p = 0.37; and CTL: 9 months 1.000 vs. 16 months 1.021 vs. 24 months 0.897, p = 0.42). CTL and LTL did not correlate ( r = −0.027, p = 0.89). No association with cardiac dysfunction was observed, neither for LTL nor CTL. Discussion Laboratory rats of high age exhibited cardiac hypertrophy and dysfunction, resembling human cardiac ageing, however we found no evidence of shorter telomere lengths in circulating leukocytes nor cardiac cells, suggesting a translational gap.

Source: Frontiers in Cardiovascular Medicine

DOI: 10.3389/fcvm.2026.1790767