Daily Melatonin Administration Attenuates Age-Dependent Disturbances of Cardiovascular Rhythms

Gubin, Denis; Губин, Г. Д.; Gapon, L.; Weinert, Dietmar

doi:10.2174/1874609809666151130220011

Cited by 55 publications

(26 citation statements)

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“…Recently, clinical trials have been developed to investigate the effect of melatonin on the treatment of age‐related diseases. Oral melatonin (4‐5 mg) has been successfully used as treatment for delirious and disturbances of cardiovascular rhythms in elderly patients . Although melatonin is potentially effective, which would lead to significant outcome benefits for aging patients, the chronic treatment of melatonin in the body may cause other physiologic side effects such as sleep disorders and circadian imbalance.…”

Section: Discussionmentioning

confidence: 99%

Melatonin regulates PARP1 to control the senescence‐associated secretory phenotype (SASP) in human fetal lung fibroblast cells

Wang

Geng

et al. 2017

Journal of Pineal Research

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Cellular senescence is an important tumor-suppressive mechanism. However, acquisition of a senescence-associated secretory phenotype (SASP) in senescent cells has deleterious effects on the tissue microenvironment and, paradoxically, promotes tumor progression. In a drug screen, we identified melatonin as a novel SASP suppressor in human cells. Strikingly, melatonin blunts global SASP gene expression upon oncogene-induced senescence (OIS). Moreover, poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, was identified as a new melatonin-dependent regulator of SASP gene induction upon OIS. Here, we report two different but potentially coherent epigenetic strategies for melatonin regulation of SASP. The interaction between the telomeric repeat-containing RNA (TERRA) and PARP-1 stimulates the SASP, which was attenuated by 67.9% (illustrated by the case of IL8) by treatment with melatonin. Through binding to macroH2A1.1, PARP-1 recruits CREB-binding protein (CBP) to mediate acetylation of H2BK120, which positively regulates the expression of target SASP genes, and this process is interrupted by melatonin. Consequently, the findings provide novel insight into melatonin's epigenetic role via modulating PARP-1 in suppression of SASP gene expression in OIS-induced senescent cells. Our studies identify melatonin as a novel anti-SASP molecule, define PARP-1 as a new target by which melatonin regulates SASP, and establish a new epigenetic paradigm for a pharmacological mechanism by which melatonin interrupts PARP-1 interaction with the telomeric long noncoding RNA(lncRNA) or chromatin.

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Section: Discussionmentioning

confidence: 99%

Melatonin regulates PARP1 to control the senescence‐associated secretory phenotype (SASP) in human fetal lung fibroblast cells

Wang

Geng

et al. 2017

Journal of Pineal Research

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“…Furthermore, circadian dysfunction accelerates cellular aging and mortality with period alterations shortening lifespan in animal models (Krishnan et al, 2012, Park et al, 2012). The decline in the robustness of the circadian system appears to arise earlier in peripheral tissues than the central brain (Gubin et al, 2016, Libert et al, 2012) underscoring the need for examination of circadian processes during middle age. Given the circadian modulation of alcohol-induced behaviors and toxicity, the need exists for a tractable model suitable for dual examination of the circadian clock and alcohol neurobiology across multiple age groups.…”

Section: Introductionmentioning

confidence: 99%

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

Nobrega

Mellers

Lyons

2017

Experimental Gerontology

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Alcohol abuse is a rising problem in middle-aged and older individuals resulting in serious health, family and economic consequences. Effective treatment necessitates the identification of factors influencing alcohol toxicity with aging. We investigated the interaction between aging, alcohol toxicity and circadian function using Drosophila as a model system. We found as wild type flies age, sensitivity to alcohol increases and circadian regulation of alcohol-induced behaviors weakens. Decreased circadian modulation is correlated with significantly greater alcohol sensitivity during the subjective day. The circadian clock modulates alcohol-induced mortality in younger flies with increased mortality following alcohol exposure at night. Older flies exhibit significantly longer recovery times following alcohol-induced sedation and increased mortality following binge-like or chronic alcohol exposure. Flies rendered arrhythmic either genetically or environmentally exhibit significantly increased alcohol sensitivity, longer recovery times and increased mortality. We hypothesize that the circadian clock phase specifically buffers behavioral and cellular alcohol sensitivity with this protection diminishing as the circadian clock weakens with age.

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“…Cry1 and Cry2-deficient mice are prone to salt sensitive hypertension due to increased activity of the adrenocortical aldosterone-producing enzyme, 3 beta-hydroxyl-steroid dehydrogenase (111). Recent studies also suggest that melatonin has multiple beneficial effects on the cardiovascular system; melatonin administration at bedtime reduces blood pressure in hypertensive patients (112). Thus, it is possible that alterations in circadian rhythm may affect melatonin levels resulting in autonomic nervous dysfunction, increased aldosterone, and subsequent hypertension.…”

Section: Hypothalamic Mechanisms Of Hypertensionmentioning

confidence: 99%

Hypothalamic and inflammatory basis of hypertension

Khor

Cai

2017

Clinical Science

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Hypertension is a major health problem with great consequences for public health. Despite its role as the primary cause of significant morbidity and mortality associated with cardiovascular disease, the pathogenesis of essential hypertension remains largely unknown. The central nervous system in general, and the hypothalamus in particular, are intricately involved in the development and maintenance of hypertension. Over the last several decades, the understanding of the brain’s role in the development of hypertension has dramatically increased. This brief review is to summarize the neural mechanisms of hypertension with a focus on neuroendocrine and neurotransmitter involvement, highlighting recent findings which suggest that hypothalamic inflammation disrupts key signaling pathways to affect the central control of blood pressure, and therefore suggesting future development of interventional strategies that exploit recent findings pertaining to the hypothalamic control of blood pressure as well as the inflammatory-sympathetic mechanisms involved in hypertension.

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Daily Melatonin Administration Attenuates Age-Dependent Disturbances of Cardiovascular Rhythms

Cited by 55 publications

References 0 publications

Melatonin regulates PARP1 to control the senescence‐associated secretory phenotype (SASP) in human fetal lung fibroblast cells

Melatonin regulates PARP1 to control the senescence‐associated secretory phenotype (SASP) in human fetal lung fibroblast cells

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

Hypothalamic and inflammatory basis of hypertension

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