Melatonin and the theories of aging: a critical appraisal of melatonin's role in antiaging mechanisms

Journal of Pineal Research, Год журнала: 2013, Номер 55(4), С. 325 - 356

Опубликована: Авг. 26, 2013

The classic theories of aging such as the free radical theory, including its mitochondria-related versions, have largely focused on a few specific processes senescence. Meanwhile, numerous interconnections become apparent between age-dependent changes previously thought to proceed more or less independently. Increased damage by radicals is not only linked impairments mitochondrial function, but also inflammaging it occurs during immune remodeling and release proinflammatory cytokines from mitotically arrested, DNA-damaged cells that exhibit senescence-associated secretory phenotype (SASP). Among other effects, SASP can cause mutations in stem reduce capacity for tissue regeneration or, worst case, lead cancer cells. Oxidative stress has been shown promote telomere attrition. Moreover, connected impaired circadian rhythmicity. Another nexus exists cellular oscillators metabolic sensing, particular aging-suppressor SIRT1, which acts an accessory clock protein. Melatonin, being highly pleiotropic regulator molecule, interacts directly indirectly with all mentioned. These influences are critically reviewed, emphasis data aged organisms senescence-accelerated animals. sometimes-controversial findings obtained either nongerontological context comparisons tumor nontumor discussed light evidence senescent organisms. Although, mammals, lifetime extension melatonin rarely documented fully conclusive way, support healthy observed rodents likely humans.

Язык: Английский

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Cancer metastasis: Mechanisms of inhibition by melatonin

Journal of Pineal Research, Год журнала: 2016, Номер 62(1)

Опубликована: Окт. 12, 2016

Abstract Melatonin is a naturally occurring molecule secreted by the pineal gland and known as gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple interrelated mechanisms, exhibits variety oncostatic properties in myriad tumors during different stages their progression. Tumor metastasis, which commonly occurs at late stage, responsible for majority cancer deaths; metastases lead to development secondary distant from primary site. In reference vast investigations have focused on tumor progression Recently, however, interest has shifted toward role melatonin metastases. this review, we highlight current advances understanding molecular mechanisms counteracts metastases, including experimental clinical observations; emphasis placed impact both non‐neoplastic cells within microenvironment. Due broad range melatonin's actions, underlying its ability interfere with are numerous. These include modulation cell–cell cell–matrix interaction, extracellular matrix remodeling metalloproteinases, cytoskeleton reorganization, epithelial–mesenchymal transition, angiogenesis. The discussed herein will serve solid foundation urging basic studies use understand control metastatic diseases.

Язык: Английский

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Exogenous Melatonin Alleviates Oxidative Damages and Protects Photosystem II in Maize Seedlings Under Drought Stress

Frontiers in Plant Science, Год журнала: 2019, Номер 10

Опубликована: Май 24, 2019

The protective role of melatonin in plants against various abiotic stresses have been widely demonstrated, but poorly explored organ-specific responses and the transmission signals across organs. In this study, effects with root-irrigation method leaf-spraying on antioxidant system photosynthetic machinery maize seedlings under drought stress were investigated. results showed that led to rise reactive oxygen species (ROS), severe cell death, degradation D1 protein, which mitigated by application. application improved activities alleviated oxidative damages stress. Compared method, was more effective enhancing tolerance. Moreover, made physiological stress, varied dosage, methods plant exogenous received roots could affect leaves, perceived leaves also changes metabolisms Consequently, whole coordinated different parts a systemic acclimation Melatonin as agent has potential prospect agricultural industry.

Язык: Английский

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Melatonin: A Versatile Protector against Oxidative DNA Damage

Molecules, Год журнала: 2018, Номер 23(3), С. 530 - 530

Опубликована: Фев. 27, 2018

Oxidative damage to DNA has important implications for human health and been identified as a key factor in the onset development of numerous diseases. Thus, it is evident that preventing from oxidative crucial humans any living organism. Melatonin an astonishingly versatile molecule this context. It can offer both direct indirect protection against wide variety damaging agents through multiple pathways, which may (or not) take place simultaneously. They include antioxidative protection, mediated by melatonin’s free radical scavenging activity, also ways action. The latter include, at least: (i) inhibition metal-induced damage; (ii) non-radical triggers (iii) continuous after being metabolized; (iv) activation enzymes; (v) pro-oxidative (vi) boosting repair machinery. rather unique capability melatonin exhibit neutralizing actions diverse threatening factors, together with its low toxicity ability cross biological barriers, are all significant efficiency DNA.

Язык: Английский

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Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model

Brain, Год журнала: 2012, Номер 136(1), С. 90 - 105

Опубликована: Ноя. 26, 2012

Despite treatment with therapeutic hypothermia, almost 50% of infants neonatal encephalopathy still have adverse outcomes. Additional treatments are required to maximize neuroprotection. Melatonin is a naturally occurring hormone involved in physiological processes that also has neuroprotective actions against hypoxic–ischaemic brain injury animal models. The objective this study was assess effects combining melatonin hypothermia after transient hypoxia–ischaemia piglet model perinatal asphyxia using clinically relevant magnetic resonance spectroscopy biomarkers supported by immunohistochemistry. After quantified global insult, 17 newborn piglets were randomized the following: (i) (33.5°C from 2 26 h resuscitation, n = 8) and (ii) plus intravenous (5 mg/kg/h over 6 started at 10 min resuscitation repeated 24 h, 9). Cortical white matter deep grey voxel proton whole 31P acquired before during hypoxia–ischaemia, 48 resuscitation. There no difference baseline variables, insult severity or any biochemical measure, including mean arterial blood pressure inotrope use hypoxia–ischaemia. Plasma levels 000 times higher than alone group. Melatonin-augmented significantly reduced hypoxic–ischaemic-induced increase area under curve for lactate/N-acetyl aspartate lactate/total creatine ratios matter. increased nucleotide triphosphate/exchangeable phosphate pool. Correlating improved cerebral energy metabolism, TUNEL-positive nuclei group compared thalamus, internal capsule, putamen caudate, there cleaved caspase 3 thalamus. Although total numbers microglia not decreased matter, expression prototypical cytotoxic microglial activation marker CD86 cortex safety neuroprotection combination cooling support phase II clinical trials moderate severe encephalopathy.

Язык: Английский

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