Telomere attrition is associated with inflammation, low fetuin‐A levels and high mortality in prevalent haemodialysis patients

Abstract

. Introduction. Chronic kidney disease (CKD) predisposes to a 10‐ to 20‐fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk. Methods. This is a cross‐sectional study in prevalent haemodialysis patients [n = 175; 98 Males; median (range) age: 66 (23–86) years]. Biochemical markers of oxidative stress and inflammatory status were measured in relation to the patient’s leucocyte telomere length. Overall mortality was assessed after a median of 31 (range 2–42) months. Results. Telomere length was shorter in CKD men, despite women being older (average ± SD 6.41 ± 1.23 vs. 6.96 ± 1.48 kb, P = 0.002). Telomere length was associated with age (rho = −0.18, P = 0.01), fetuin‐A (rho = 0.26, P = 0.0004), high‐sensitivity C‐reactive protein (rho = −0.21, P = 0.005) and IL‐6 (rho = −0.17, P = 0.02). In a multivariate logistic regression (pseudo r2 = 0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95% CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin‐A (1.85; 0.97, 3.50) and white blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally, reduced telomere length was associated with increased mortality, independently of age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently on fetuin‐A levels. Conclusion. Age and male gender seem to be important contributors to reduced telomere length in CKD patients, possibly via persistent inflammation. Reduced telomere length also contributes to the mortality risk of these patients through pathways that could involve circulating levels of fetuin‐A.

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

“…Stress is transduced from the pregnant mother to her fetus through various pathways, including transplacental transport of the stress hormone cortisol, maternal stress-induced release of placental hormones that enter the fetal circulation (e.g., placental corticotrophin-releasing hormone), and maternal stress-induced effects on placental physiology, including alterations in blood flow and changes in metabolism impacting oxygen and glucose availability and use (52,53). Exposure to high levels of maternal stress hormones during pregnancy is known to produce deleterious effects on the offspring's developing immune system (32, 54, 55), and our previously published studies in this cohort have reported that the prenatally stressed individuals exhibited alterations in several immune parameters (33), including higher phytohemagglutinin-stimulated levels of IL-6, a proinflammatory cytokine that has been associated with shorter telomere length (56,57). We also have found that the prenatally stressed individuals in this cohort exhibited insulin and leptin resistance, as well as a higher BMI (31).…”

Telomeric G-Tail Length and Hospitalization for Cardiovascular Events in Hemodialysis Patients

“…Clinical studies have shown that total telomere shortening is associated with increasing chronological age (6,7), progression of arteriosclerosis (8,9), and CKD (10)(11)(12). Patients with CKD have a markedly increased risk for cardiovascular disease (CVD) (13) and total telomere shortening is associated with progression of CVD (14).…”

Biological Ageing Research in Systemic Sclerosis: Time to Grow up?

“…The length of telomeric DNA repeats shortens during the ageing of cultured somatic cells ( e.g. fibroblasts, peripheral blood lymphocytes and colon epithelia), but the rate of shortening is also under both polygenic and environmental influences (15,16). As a consequence, telomere length reflects the "miles on the clock" of a given individual or cell type.…”