Melatonin and inflammation—Story of a double‐edged blade

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 65(4)

Published: Sept. 22, 2018

Melatonin is an immune modulator that displays both pro- and anti-inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte-derived cell lines, can be assumed to enhance the resistance against pathogens. However, they detrimental autoimmune diseases. Anti-inflammatory actions of particular medicinal interest, because observed high-grade inflammation such as sepsis, ischemia/reperfusion, brain injury, also low-grade during aging neurodegenerative The mechanisms contributing effects manifold comprise various pathways secondary signaling. These include numerous antioxidant effects, downregulation inducible inhibition neuronal NO synthases, cyclooxygenase-2, high-mobility group box-1 signaling toll-like receptor-4 activation, prevention inflammasome NLRP3 NF-κB activation upregulation nuclear factor erythroid 2-related 2 (Nrf2). reflected proinflammatory cytokines. amyloid-β peptides reduced enhancing α-secretase β- γ-secretases. A role melatonin's seems associated with sirtuin-1 (SIRT1), shares known from melatonin additionally interferes mechanistic target rapamycin (mTOR) Notch, reduces expression lncRNA-CCL2. conclusion on a partial mediation SIRT1 supported repeatedly inhibitions sirtuin inhibitors knockdown.

Language: Английский

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Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

Molecules, Journal Year: 2018, Volume and Issue: 23(2), P. 509 - 509

Published: Feb. 24, 2018

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or exposed toxins. Oxidative damage is a result free radicals produced in cells, especially mitochondria. When measured, melatonin, potent antioxidant, was found be higher concentrations mitochondria than other organelles subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters aid rapid uptake melatonin by these against gradient. Moreover, we predicted several years ago that, because their origin from melatonin-producing bacteria, likely also synthesize melatonin. Data accumulated within last year supports this prediction. A high content would fortuitous, since produce an abundance radicals. Thus, optimally positioned scavenge and degree damage. In light “free radical theory aging”, including all iterations, levels expected protect age-related organismal decline. Also, there are many age-associated diseases have, as contributing factor, These multiple may deferred onset progression if can maintained into advanced age.

Language: Английский

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Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence

Frontiers in Endocrinology, Journal Year: 2019, Volume and Issue: 10

Published: Nov. 21, 2019

Reproductive capacity in women starts to decline beyond their mid-30s and pregnancies older result higher rates of miscarriage with aneuploidy. Age-related fertility is strongly attributed ovarian aging, diminished reserves, decreased developmental competence oocytes. In this review, we discuss the underlying mechanisms age-related oocyte quality, focusing on oxidative stress (OS) The primary cause accumulation spontaneous damage mitochondria arising from increased reactive oxygen species (ROS) oocytes, generated by themselves during daily biological metabolism. Mitochondrial dysfunction reduces ATP synthesis influences meiotic spindle assembly responsible for chromosomal segregation. Moreover, reproductively aged oocytes produce a fidelity protective against ROS, namely ROS-scavenging metabolism, repair ROS-damaged DNA, proteasome autophagy system proteins. Accordingly, ROS vulnerability lead instability, abnormalities, telomere shortening, reduced

Language: Английский

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Melatonin and Cancer Hallmarks

Molecules, Journal Year: 2018, Volume and Issue: 23(3), P. 518 - 518

Published: Feb. 26, 2018

Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of circadian rhythm. Many studies have reported anticancer effect melatonin against myriad cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion. activity mediated interfering with various hallmarks. This review summarizes role in each hallmark. The discussed this should serve as solid foundation for researchers physicians to support basic clinical on promising agent.

Language: Английский

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Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1135 - 1135

Published: Feb. 8, 2020

Melatonin is probably produced in all cells but only secreted by the pineal gland. The secretion of melatonin determined light–dark cycle, and it released at night. regulates biological rhythms via its receptors located suprachiasmatic nuclei hypothalamus. also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). direct radical scavenging actions are receptor independent. ROS play an important role reproductive function including ovulatory process. However, excessive can have adverse effect on oocytes because oxidative stress, thereby causing infertility. It becoming clear that ovarian follicular fluid themselves, which protects these from damage well having other beneficial oocyte maturation, fertilization, embryo development. Trials humans investigated improvement outcomes assisted technology (ART), vitro fertilization transfer (IVF-ET), way administering patients suffering In addition, clinical research examined anti-aging molecule antioxidative actions, relationship with aging diseases, e.g., Alzheimer’s Parkinson’s disease, underway. may reduce aging, a major issue technology. This review explains between human function, applications expected improve IVF, while discussing possibilities for preventing aging.

Language: Английский

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Environment, Lifestyle, and Female Infertility

Reproductive Sciences, Journal Year: 2020, Volume and Issue: 28(3), P. 617 - 638

Published: Aug. 3, 2020

Language: Английский

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The role of cellular senescence in female reproductive aging and the potential for senotherapeutic interventions

Human Reproduction Update, Journal Year: 2021, Volume and Issue: 28(2), P. 172 - 189

Published: Nov. 11, 2021

Advanced maternal age is associated with decreased oocyte quantity and quality as well uterine placental dysfunctions. These changes lead to infertility, pregnancy complications birth defects in the offspring. As mean of giving increasing worldwide, prevention age-associated infertility complications, along more frequent use ART, become extremely important. Currently, significant research being conducted unravel mechanisms underlying female reproductive aging. Among potential involved, recent evidence has suggested a contributing role for cellular senescence, state irreversible growth arrest characterized by hypersecretory pro-inflammatory phenotype. Elucidating senescence aging holds developing novel less invasive therapeutic measures prevent or even reverse increase offspring wellbeing.

Language: Английский

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Inhibition of the NLRP3 inflammasome prevents ovarian aging

Science Advances, Journal Year: 2021, Volume and Issue: 7(1)

Published: Jan. 1, 2021

Inflammation is a hallmark of aging and negatively affecting female fertility. In this study, we evaluate the role NLRP3 inflammasome in ovarian Age-dependent increased expression ovary was observed WT mice during reproductive aging. High NLRP3, caspase-1, IL-1β also granulosa cells from patients with insufficiency. Ablation improved survival pregnancy rates anti-Müllerian hormone levels autophagy ovaries. Deficiency reduced serum FSH estradiol levels. Consistent these results, pharmacological inhibition using direct inhibitor, MCC950, fertility to comparable those Nlrp3-/- mice. These results suggest that implicated age-dependent loss position as potential new therapeutic target for treatment infertility.

Language: Английский

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Evidence for the Benefits of Melatonin in Cardiovascular Disease

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 20, 2022

The pineal gland is a neuroendocrine which produces melatonin, hormone with critical physiological roles in the circadian rhythm and sleep-wake cycle. Melatonin has been shown to possess anti-oxidant activity neuroprotective properties. Numerous studies have that melatonin significant functions cardiovascular disease, may anti-aging ability of decrease primary hypertension needs be more extensively evaluated. benefits reducing cardiac pathology, preventing death muscle response ischemia-reperfusion rodent species. Moreover, also prevent hypertrophy heart under some circumstances, turn would lessen development failure. Several currently used conventional drugs show cardiotoxicity as an adverse effect. Recent acts effective suppressing damage mediated by pharmacologic drugs. Therefore, cardioprotective multiple animal human studies. Herein, we summarize most established system focus on molecular mechanisms action.

Language: Английский

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Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Language: Английский

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