Cross-species Association Between Telomere Length and Glucocorticoid Exposure

Lee, Richard S.; Zandi, Peter P.; Santos, Alicia; Aulinas, Anna; Carey, Jenny L.; Webb, Susan M.; McCaul, Mary E.; Resmini, Eugenia; Wand, Gary S.

doi:10.1210/clinem/dgab519

Cited by 8 publications

(4 citation statements)

References 76 publications

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“…A significant correlation between plasma cortisol and HDL cholesterol and body mass index suggests that glucocorticoids regulate critical components of cardiovascular risks ( 47 ). Exposure to stress or glucocorticoids is associated with shortened telomeres in rats ( 48 ). Corticosterone exposure impairs emotional regulation and cognitive function in mice ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

TRPV6 deficiency attenuates stress and corticosterone-mediated exacerbation of alcohol-induced gut barrier dysfunction and systemic inflammation

et al. 2023

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IntroductionChronic stress is co-morbid with alcohol use disorder that feedback on one another, thus impeding recovery from both disorders. Stress and the stress hormone corticosterone aggravate alcohol-induced intestinal permeability and liver damage. However, the mechanisms involved in compounding tissue injury by stress/corticosterone and alcohol are poorly defined. Here we explored the involvement of the TRPV6 channel in stress (or corticosterone) 3and alcohol-induced intestinal epithelial permeability, microbiota dysbiosis, and systemic inflammation. MethodsChronic alcohol feeding was performed on adult wild-type and Trpv6-/- mice with or without corticosterone treatment or chronic restraint stress (CRS). The barrier function was determined by evaluating inulin permeability in vivo and assessing tight junction (TJ) and adherens junction (AJ) integrity by immunofluorescence microscopy. The gut microbiota composition was evaluated by 16S rRNA sequencing and metagenomic analyses. Systemic responses were assessed by evaluating endotoxemia, systemic inflammation, and liver damage.ResultsCorticosterone and CRS disrupted TJ and AJ, increased intestinal mucosal permeability, and caused endotoxemia, systemic inflammation, and liver damage in wild-type but not Trpv6-/- mice. Corticosterone and CRS synergistically potentiated the alcohol-induced breakdown of intestinal epithelial junctions, mucosal barrier impairment, endotoxemia, systemic inflammation, and liver damage in wild-type but not Trpv6-/- mice. TRPV6 deficiency also blocked the effects of CRS and CRS-mediated potentiation of alcohol-induced dysbiosis of gut microbiota. ConclusionsThese findings indicate an essential role of TRPV6 in stress, corticosterone, and alcohol-induced intestinal permeability, microbiota dysbiosis, endotoxemia, systemic inflammation, and liver injury. This study identifies TRPV6 as a potential therapeutic target for developing treatment strategies for stress and alcohol-associated comorbidity.

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Section: Discussionmentioning

confidence: 99%

TRPV6 deficiency attenuates stress and corticosterone-mediated exacerbation of alcohol-induced gut barrier dysfunction and systemic inflammation

et al. 2023

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“…Furthermore, the summary data showed that most SLE cases in these studies received treatments which may lead to telomere shortening. For example, Lee et al showed that exposure to glucocorticoids is associated with a significant reduction of telomere length in both mice and humans (20).…”

Section: Discussionmentioning

confidence: 99%

Telomere Length and Development of Systemic Lupus Erythematosus: A Mendelian Randomization Study

Wang

et al. 2022

Arthritis & Rheumatology

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Objective. Previous observational studies demonstrated that a subset of patients with systemic lupus erythematosus (SLE) have markedly short telomere length in leukocytes. This study was undertaken to test whether leukocyte telomere length is causally associated with risk of SLE.Methods. A 2-sample Mendelian randomization (MR) analysis was conducted to estimate causality of telomere length on SLE in European populations. A replication 2-sample MR study using Asian genetic data was also conducted. A reverse MR analysis was then performed to test the effects of SLE on telomere length. The autoantibodies targeting telomere-associated protein (telomeric repeat-binding factor 1 [TERF1] autoantibodies) were detected in patients with SLE, healthy controls, and patients with rheumatoid arthritis.Results. The results of the inverse variance-weighted method (odds ratio [OR] 2.96 [95% confidence interval (95% CI) 1.58-5.55], P < 0.001) showed strong evidence for a causal relationship between longer telomere length and risk of SLE in people with European ancestry. The outcomes of MR-Egger regression analysis ], P = 0.033) and MR pleiotropy residual sum and outlier analysis (OR 3.62 [95% CI 2.03-6.46], P = 0.002) also showed that longer telomere length was significantly associated with increased risk of SLE in a European population. Sensitivity analyses using different methods and summary data sets showed that the results were still broadly consistent. A replication MR study using Asian genetic data yielded similar findings. However, the reverse MR analysis showed that genetically predicted SLE was not causally associated with telomere length. In addition, we found that TERF1 autoantibodies were present in 2 of 40 SLE patients (5.0%).Conclusion. In contrast with previous observational studies, MR analyses show that longer telomere length is significantly associated with increased risk of SLE.Available data have suggested that telomere length is associated with inflammation and immunity (1), which indicated that there might be potential linkage between telomere length and risk of SLE. To date, considerable observational studies have compared telomere length in SLE patients with that of healthy controls. In the majority of these studies (2-4), telomere length was found to become shorter in SLE patients compared to healthy controls. A previous meta-analysis tried to combine these

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“…O.A. Savchenko 1,2 ПЦР (qPCR) в реальном времени на основе методики Lee RS с соавторами (2021) [37] с модификациями [38]. ДНК выделена методом фенолхлороформной экстракции [39]…”

Section: Risk Meters and Markers Of Accelerated Agingunclassified

Risk meters and markers of accelerated aging

Savchenko,

Novikova,

Plotnikova

et al. 2024

Scientific Bulletin of the Omsk State Medical University

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The purpose of the study is to analyze scientific research on the establishment of risk meters and markers of aging, in order to take a set of measures to prevent accelerated aging and the development of occupational diseases in the working population, including using models on laboratory animals. Material and methods: analytical, toxicological, hygienic and statistical research methods. The object of the study was the results of our own original research on the influence of environmental factors (vibration, noise, 4-component mixture of hydrocarbons) on the organisms of model animals, as well as published research material on the establishment of risk meters and markers of aging. The results and their discussion. The study determined a direct relationship between gender, age and duration of exposure to environmental factors on model organisms exposed to 90-day exposure to occupational hazards, which made it possible to establish risk meters and markers of premature aging in animals of experimental groups, compared with the control group. The results obtained experimentally will contribute to the adoption of measures to protect the health of the labor contingent. Conclusion. The leading role of timely adoption of a set of health-saving measures to prevent the development of occupational diseases in the labor contingent is determined, based on established risk meters and markers of accelerated aging using organisms of model animals.

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Cross-species Association Between Telomere Length and Glucocorticoid Exposure

Cited by 8 publications

References 76 publications

TRPV6 deficiency attenuates stress and corticosterone-mediated exacerbation of alcohol-induced gut barrier dysfunction and systemic inflammation

TRPV6 deficiency attenuates stress and corticosterone-mediated exacerbation of alcohol-induced gut barrier dysfunction and systemic inflammation

Telomere Length and Development of Systemic Lupus Erythematosus: A Mendelian Randomization Study

Risk meters and markers of accelerated aging

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