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

Context: Chronic psychological stress has been associated with shorter telomeres in some studies, but the underlying mechanisms are poorly understood. One possibility is that the neuroendocrine responses associated with stress exposure are involved. Objective: To testing the hypothesis that greater cortisol responsivity to acute stressors predicts more rapid telomere attrition. Design: We measured salivary cortisol responses to two 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 54-76 years. Main outcome measure: Leukocyte telomere length. Results: Cortisol responses to this protocol were small, we divided participants into cortisol responders (n = 156) and non-responders (n = 255) using a criterion (≥20%) 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 non-responders on follow-up, after controlling statistically for age, gender, socioeconomic status, smoking, time of day of stress testing 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 non-responders 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

Short sleep duration is associated with shorter telomere length in healthy men: findings from the Whitehall II cohort study

Background: Shorter telomere length and poor sleep are more prevalent at older ages, but their relationship is uncertain. This study explored associations between sleep duration and telomere length in a sample of healthy middle and early old age people. Methods: Participants were 434 men and women aged 63.3 years on average drawn from the Whitehall II cohort study. Sleep duration was measured by self-report. Results: There was a linear association between sleep duration and leukocyte telomere length in men but not in women (P = 0.035). Men reporting shorter sleep duration had shorter telomeres, independently of age, body mass index, smoking, educational attainment, current employment, cynical hostility scores and depressive symptoms. Telomeres were on average 6% shorter in men sleeping 5 hours or fewer compared with those sleeping more than 7 hours per night. Conclusion: This study adds to the growing literature relating sleep duration with biomarkers of aging, and suggests that shortening of telomeres might reflect mechanisms through which short sleep contributes to pathological conditions in older men

The age-dependent association between aortic pulse wave velocity and telomere length.

KEY POINTS: Age significantly modifies the relationship between aortic pulse wave velocity and telomere length. The differential relationships observed between aortic pulse wave velocity and telomere length in younger and older individuals suggest that the links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course. ABSTRACT: Ageing is associated with marked large artery stiffening. Telomere shortening, a marker of cellular ageing, is linked with arterial stiffening. However, the results of existing studies are inconsistent, possibly because of the confounding influence of variable exposure to cardiovascular risk factors. Therefore, we investigated the relationship between telomere length (TL) and aortic stiffness in well-characterized, younger and older healthy adults, who were pre-selected on the basis of having either low or high aortic pulse wave velocity (aPWV), a robust measure of aortic stiffness. Demographic, haemodynamic and biochemical data were drawn from participants in the Anglo-Cardiff Collaborative Trial. Two age groups with an equal sex ratio were examined: those aged 50 years (older). Separately for each age group and sex, DNA samples representing the highest (n = 125) and lowest (n = 125) extremes of aPWV (adjusted for blood pressure) were selected for analysis of leukocyte TL. Ultimately, this yielded complete phenotypic data on 904 individuals. In younger subjects, TL was significantly shorter in those with high aPWV vs. those with low aPWV (P = 0.017). By contrast, in older subjects, TL was significantly longer in those with high aPWV (P = 0.001). Age significantly modified the relationship between aPWV and TL (P < 0.001). Differential relationships are observed between aPWV and TL, with an inverse association in younger individuals and a positive association in older individuals. The links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course.Professor Ian B. Wilkinson is a British Heart Foundation Senior Fellow (FS/12/8/29377). Dr Yasmin is supported by the British Heart Foundation (FS/12/8/29377). This work was also supported by the National Institute for Health Research, Cambridge Biomedical Research Centre Award

Highlights of the 2nd International Symposium on Tribbles and Diseases: Tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

The Tribbles (TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2nd International Symposium on Tribbles and Diseases held on May 7‒9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases

Defining an ageing-related pathology, disease or syndrome: International Consensus Statement

Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes

Vascular endothelial senescence: from mechanisms to pathophysiology

Most mitotically competent mammalian cell types can react to stress by undergoing a phenotypically distinctive and permanent form of growth arrest called “cellular senescence.” This response has been extensively characterized in cell culture and more recently it has been found to occur also in vivo in a number of tissues. In this review I will present the case for the occurrence of senescence in the vascular endothelium. I will also discuss the mechanisms and factors that modulate endothelial cell replicative capacity and the onset of senescence. Finally, I will examine the senescent phenotype and its possible consequences for the development and progression of vascular diseases