Telomere length analysis in Cushing's syndrome

Aulinas, Anna; Ramírez, María-José; Barahona, María José; Valassi, Elena; Resmini, Eugenia; Mato, Eugènia; Santos, Alicia; Crespo, Iris; Bell, Olga; Surrallés, Jordi; Webb, Susan M.

doi:10.1530/eje-14-0098

Cited by 19 publications

(14 citation statements)

References 29 publications

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“…Our study builds on these findings by establishing a longitudinal relationship, because cortisol responsivity predicted telomere shortening over time. The results are also consistent with longitudinal clinical studies indicating that telomere length is shorter during active Cushing’s syndrome than when patients are in remission ( 34 ).…”

Section: Discussionsupporting

confidence: 88%

The longitudinal relationship between cortisol responses to mental stress and leukocyte telomere attrition

Steptoe

Hamer

Lin

et al. 2016

The Journal of Clinical Endocrinology & Metabolism

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Context:Chronic psychological stress has been associated with shorter telomeres, but the underlying mechanisms are poorly understood. One possibility is that the neuroendocrine responses to stress exposure are involved.Objective:To test the hypothesis that greater cortisol responsivity to acute stressors predicts more rapid telomere attrition.Design:We measured salivary cortisol responses to 2 challenging behavioral tasks. Leukocyte telomere length was measured at the time of mental stress testing and 3 years later.Participants:We studied 411 initially healthy men and women aged 54 to 76 years.Main outcome measure:Leukocyte telomere length.Results:Cortisol responses to this protocol were small; we divided participants into cortisol responders (n = 156) and nonresponders (n = 255) using a criterion (≥20% increase in cortisol concentration) previously shown to predict increases in cardiovascular disease risk. There was no significant association between cortisol responsivity and baseline telomere length, although cortisol responders tended to have somewhat shorter telomeres (β = −0.061; standard error, 0.049). But cortisol responders had shorter telomeres and more rapid telomere attrition than nonresponders on follow-up, after controlling statistically for age, sex, socioeconomic status, smoking, time of day of stress , and baseline telomere length (β = −0.10; standard error, 0.046; P = 0.029). The association was maintained after additional control for cardiovascular risk factors (β = −0.11; P = 0.031). The difference between cortisol responders and nonresponders was equivalent to approximately 2 years in aging.Conclusions:These findings suggest that cortisol responsivity may mediate, in part, the relationship between psychological stress and cellular aging.

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Section: Discussionsupporting

confidence: 88%

The longitudinal relationship between cortisol responses to mental stress and leukocyte telomere attrition

Steptoe

Hamer

Lin

et al. 2016

The Journal of Clinical Endocrinology & Metabolism

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“…Leukocyte telomere length associations with resting cortisol concentrations are less clear, with reports of an inverse correlation (Epel et al, 2006) and of no significant correlation (Parks et al, 2009). In Cushing’s syndrome, LTL and cortisol levels were not significantly related cross-sectionally, but LTL significantly lengthened after remission from the active disease (Aulinas et al, 2013a; Aulinas et al, 2014; Aulinas et al, 2013b). Studies are more, but not always, consistent in showing inverse relationships between LTL and dynamic aspects of cortisol secretion (e.g., waking-associated increases in cortisol or cortisol responses provoked by psychological stress) (Gotlib et al, 2014; Kroenke et al, 2011; Revesz et al, 2013; Tomiyama et al, 2012) as opposed to basal, resting or even circadian cortisol levels.…”

Section: Potential Mediators Of Telomere Shortening In Psychiatricmentioning

confidence: 87%

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Lindqvist

Epel

Mellon³

et al. 2015

Neuroscience & Biobehavioral Reviews

268

231

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Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURESJL is a consultant to Telomere Diagnostics Inc., formerly Telome Health, and owns stock in the company. The company had no role in this research or in writing this review. The remaining authors report no current disclosures or conflicts of interest. HHS Public Access

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“…Most studies on TL have been performed in healthy subjects, T2DM, cardiovascular disease or psychiatric conditions. We recently reported no differences in TL in a cross-sectional comparison of CS and controls, but when patients with active CS were evaluated longitudinally after biochemical control, telomere lengthening was observed despite being on average 3 years older [ 16 ]. However, no study has reported data on TL in CS related to metabolic or inflammatory state.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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Telomere length analysis in Cushing's syndrome

Cited by 19 publications

References 29 publications

The longitudinal relationship between cortisol responses to mental stress and leukocyte telomere attrition

The longitudinal relationship between cortisol responses to mental stress and leukocyte telomere attrition

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

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

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