Dyslipidemia and Chronic Inflammation Markers Are Correlated with Telomere Length Shortening in Cushing’s Syndrome

Abstract

IntroductionCushing’s syndrome (CS) increases cardiovascular risk (CVR) and adipocytokine imbalance, associated with an increased inflammatory state. Telomere length (TL) shortening is a novel CVR marker, associated with inflammation biomarkers. We hypothesized that inflammatory state and higher CVR in CS might be related to TL shortening, as observed in premature aging.AimTo evaluate relationships between TL, CVR and inflammation markers in CS.MethodsIn a cross-sectional study, 77 patients with CS (14 males, 59 pituitary-, 17 adrenal- and 1 ectopic-origin; 21 active disease) and 77 age-, gender-, smoking-matched controls were included. Total white blood cell TL was measured by TRF-Southern technique. Clinical data and blood samples were collected (lipids, adrenal function, glucose). Adiponectin, interleukin-6 (IL6) and C-reactive protein (CRP) were available in a subgroup of patients (n=32). Correlations between TL and clinical features were examined and multiple linear regression analysis was performed to investigate potential predictors of TL.ResultsDyslipidemic CS had shorter TL than non-dyslipidemic subjects (7328±1274 vs 7957±1137 bp, p<0.05). After adjustment for age and body mass index, cured and active CS dyslipidemic patients had shorter TL than non-dyslipidemic CS (cured: 7187±1309 vs 7868±1104; active: 7203±1262 vs 8615±1056, respectively, p<0.05). Total cholesterol and triglycerides negatively correlated with TL (r-0.279 and -0.259, respectively, p<0.05), as well as CRP and IL6 (r-0.412 and -0.441, respectively, p<0.05). No difference in TL according the presence of other individual CVR factors (hypertension, diabetes mellitus, obesity) were observed in CS or in the control group. Additional TL shortening was observed in dyslipidemic obese patients who were also hypertensive, compared to those with two or less CVR factors (6956±1280 vs 7860±1180, respectively, p<0.001). Age and dyslipidemia were independent negative predictors of TL.ConclusionTL is shortened in dyslipidemic CS patients, further worse if hypertension and/or obesity coexist and is negatively correlated with increased inflammation markers. Increased lipids and a “low” grade inflammation may contribute to TL shortening and consequently to premature ageing and increased morbidity in CS.

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout

“…The results of our study underline the strong association between inflammation, senescence and cardiovascular disease, as suggested previously 35. Recently, it has become apparent that rheumatic diseases confer risk of cardiovascular disease development.…”

Increased oxidative stress, inflammation and fibrosis in perirenal adipose tissue of patients with cortisol-producing adenoma

“…The authors also reported [16] that dexamethasone inhibited macrophage recruitment in mature 3T3-L1 cells. The plasma IL-6 level of patients with Cushing's syndrome was increased compared with normal controls [17]. Researchers have found that, despite long-term cure, plasma inflammation markers, including TNF alphareceptor 1 and IL-6, were higher in Cushing's syndrome patients than in matched healthy controls [18].…”

Exercise Influences in Depressive Disorders: Symptoms, Biomarkers and Telomeres

“…TTAGGG repeats are lost from telomeres as the cells proliferate, the so-called 'end-replication problem' , linked to DNA damage response and apoptosis [12]. They may be viewed as biological clocks since short, or 'shortened' , telomeres are linked not only with age-related diseases, disease-specific and all-cause mortality [13][14][15], despite the lack of any relationship between telomere length and subjective age that was observed also [16], but also psychiatric conditions such as schizophrenia [17][18][19]. Notwithstanding the lack of result [16], there is a consensus that telomere length shortens with each cell division and with increasing chronological age and short telomeres have been associated with a range of age-related diseases.…”