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Molecules (Basel, Switzerland) Feb 2018Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative... (Review)
Review
Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters that aid in the rapid uptake of melatonin by these organelles against a gradient. Moreover, we predicted several years ago that, because of their origin from melatonin-producing bacteria, mitochondria likely also synthesize melatonin. Data accumulated within the last year supports this prediction. A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the "free radical theory of aging", including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age.
Topics: Aging; Animals; Antioxidants; Free Radicals; Humans; Melatonin; Mitochondria; Organ Specificity; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative Stress; Reactive Oxygen Species
PubMed: 29495303
DOI: 10.3390/molecules23020509 -
Biomolecules Dec 2023Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risk of falls, frailty, and mortality.... (Review)
Review
Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risk of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria and organelle, where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.
Topics: Humans; Sarcopenia; Melatonin; Aging; Muscle, Skeletal; Oxidative Stress
PubMed: 38136651
DOI: 10.3390/biom13121779 -
Frontiers in Bioscience (Scholar... Jan 2013Generation of circadian oscillations is based on rhythmic expression of clock genes and subsequent post-transcriptional and post-translational modifications. In addition... (Review)
Review
Generation of circadian oscillations is based on rhythmic expression of clock genes and subsequent post-transcriptional and post-translational modifications. In addition to the central circadian oscillator - the suprachiasmatic nucleus (SCN), peripheral oscillators have been demonstrated in many tissues, including the heart and blood vessels. Melatonin mediates cyclic lighting conditions to rhythmic endocrine signal and is able to synchronize neuronal firing in the SCN via membrane receptors. Clock gene expression is melatonin sensitive in the pars tuberalis, genes cry1 and tim1 respond to single injection while neurod1 and npas4 are influenced via long lasting mechanisms. In the rat heart, melatonin phase advanced expression of per2 and bmal1 independently from its effects on the SCN. Melatonin is an important endogenous signal able to synchronize circadian oscillations in the cardiovascular system. It may be effective especially in situations when the circadian control is weakened or organism must adapt to rapid changes in rhythmic environmental conditions.
Topics: Animals; Cardiovascular Physiological Phenomena; Circadian Rhythm; Gene Expression Regulation; Humans; Melatonin; Photoperiod
PubMed: 23277083
DOI: 10.2741/s404 -
International Journal of Molecular... Feb 2019Melatonin is a multifunctional signaling molecule, ubiquitously distributed in different parts of plants and responsible for stimulating several physiological responses... (Review)
Review
Melatonin is a multifunctional signaling molecule, ubiquitously distributed in different parts of plants and responsible for stimulating several physiological responses to adverse environmental conditions. In the current review, we showed that the biosynthesis of melatonin occurred in plants by themselves, and accumulation of melatonin fluctuated sharply by modulating its biosynthesis and metabolic pathways under stress conditions. Melatonin, with its precursors and derivatives, acted as a powerful growth regulator, bio-stimulator, and antioxidant, which delayed leaf senescence, lessened photosynthesis inhibition, and improved redox homeostasis and the antioxidant system through a direct scavenging of reactive oxygen species (ROS) and reactive nitrogen species (RNS) under abiotic and biotic stress conditions. In addition, exogenous melatonin boosted the growth, photosynthetic, and antioxidant activities in plants, confirming their tolerances against drought, unfavorable temperatures, salinity, heavy metals, acid rain, and pathogens. However, future research, together with recent advancements, would support emerging new approaches to adopt strategies in overcoming the effect of hazardous environments on crops and may have potential implications in expanding crop cultivation against harsh conditions. Thus, farming communities and consumers will benefit from elucidating food safety concerns.
Topics: Adaptation, Physiological; Antioxidants; Melatonin; Plant Growth Regulators; Plant Physiological Phenomena; Stress, Physiological
PubMed: 30818835
DOI: 10.3390/ijms20051040 -
International Journal of Biological... 2023A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in...
A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in neuroprotective activities, immune system regulation and suppression of inflammatory responses. This study set out to provide evidence that melatonin improves muscle regeneration during skeletal muscle differentiation. We began with cloning a stable cell line expressing Pax7 knockdown C2C12 cells. We then investigated markers of muscle degradation and regeneration after treating growth medium and differentiated medium with melatonin. Bioinformatics analysis of RNA sequencing results revealed that melatonin regulates muscle differentiation and that Wnt cascades are involved in the mechanism of muscle differentiation. Screening of miRNA online databases revealed that miR-3475-3p is a specific binding site on Pax7 and acts as a negative regulator of Pax7, which is involved in melatonin-induced muscle differentiation. We then investigated the effects of melatonin treatment in the early stage of glycerol-induced skeletal muscle injury in mice. Rotarod performance, micro-computed tomography and immunohistochemistry findings showed that melatonin-induced increases in Pax7 expression rapidly rescue skeletal muscle differentiation and improve muscle fiber morphology in glycerol-induced muscle injury. Our data support the hypothesis that melatonin rapidly rescues skeletal muscle differentiation and the melatonin/Pax7 axis could therefore serve as an important therapeutic target to optimize muscle healing after injury.
Topics: Animals; Mice; Melatonin; Glycerol; X-Ray Microtomography; Myoblasts; Cell Differentiation; Muscle, Skeletal; Muscle Development; Cell Proliferation; PAX7 Transcription Factor
PubMed: 36923937
DOI: 10.7150/ijbs.79169 -
Investigative Ophthalmology & Visual... Aug 2023This study aimed to investigate the age-dependent anti-angiogenic capability of melatonin in choroidal neovascularization (CNV) and to explore the underlying molecular...
PURPOSE
This study aimed to investigate the age-dependent anti-angiogenic capability of melatonin in choroidal neovascularization (CNV) and to explore the underlying molecular mechanisms.
METHODS
In the present study, a laser-induced CNV model was established in both young (three months of age) and old (18 months of age) mice, and the size of CNV lesions and vascular leakage was detected by morphological and imaging examination. Next, Western blot and immunostaining were used to observe the levels of M2 markers, senescence-related markers, and molecules involved in IL-10/STAT3 pathway. Additionally, colivelin was used to study the effect of IL-10/STAT3 pathway activation on the expression of M2 markers and senescence-related markers by Western blot and immunostaining. Finally, the effects of colivelin on melatonin-induced reduction of CNV size and vascular leakage in mice at different ages were assessed using morphological and imaging examination.
RESULTS
Our results revealed that aging promoted M2 macrophage/microglia polarization, and aggravated CNV and vascular leakage. Melatonin significantly inhibited the M2 polarization of senescent macrophage/microglia and reduced the CNV area and vascular leakage. Moreover, melatonin markedly suppressed IL-10/STAT3 pathway activation in the macrophage/microglia of old mice, and STAT3 activator colivelin reversed the suppressive effect of melatonin on M2 polarization of senescent macrophage/microglia and laser-induced CNV in old mice.
CONCLUSIONS
Our data demonstrated that melatonin significantly prevented the M2 polarization of senescent macrophage/microglia by inhibiting the IL-10/STAT3 pathway, and eventually attenuated senescence-associated CNV. These findings suggested that melatonin could serve as a promising therapeutic agent to treat CNV and other age-related ocular diseases.
Topics: Mice; Animals; Microglia; Melatonin; Interleukin-10; Choroidal Neovascularization; Macrophages; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37578424
DOI: 10.1167/iovs.64.11.19 -
Revista de Neurologia Sep 2002This review has been prepared in response to the increasing interest shown in understanding the part played by melatonin in the body, which has led to the search for new... (Review)
Review
OBJECTIVE
This review has been prepared in response to the increasing interest shown in understanding the part played by melatonin in the body, which has led to the search for new uses of it in cerebral disorders, such as sleep disorders including insomnia, irritability, depression, behaviour disorders and even the treatment of autism, since sleep disorders also occur in this condition. We pay particular attention to studies involving epilepsy.
DEVELOPMENT
We show that interest in melatonin is rapidly increasing and new discoveries are being made of the part it plays in the biological regulation of circadian rhythm, sleep, mood, ageing, tumour growth and reproduction. Perhaps these processes between them have led to its use in the treatment of many current problems such as neuroprotection, migraine and the control of epileptic seizures.
CONCLUSIONS
It has been shown that in both children and adults melatonin is of low toxicity and may be used in high risk persons. In this paper we make a careful analysis of recent publications in the medical literature dealing with the use of melatonin in the control of epileptic seizures and discuss its advantages and disadvantages. However, as with other types of treatment, further study, both experimental and otherwise, is necessary for confirmation.
Topics: Anticonvulsants; Circadian Rhythm; Electroencephalography; Epilepsy; Humans; Light; Melatonin; Neurons; Sleep; Sleep Wake Disorders
PubMed: 12373656
DOI: No ID Found -
International Journal of Molecular... Oct 2019When exposed to hostile environments such as radiation, physical injuries, chemicals, pollution, and microorganisms, the skin requires protective chemical molecules and... (Review)
Review
When exposed to hostile environments such as radiation, physical injuries, chemicals, pollution, and microorganisms, the skin requires protective chemical molecules and pathways. Melatonin, a highly conserved ancient molecule, plays a crucial role in the maintenance of skin. As human skin has functional melatonin receptors and also acts as a complete system that is capable of producing and regulating melatonin synthesis, melatonin is a promising candidate for its maintenance and protection. Below, we review the studies of new metabolic pathways involved in the protective functions of melatonin in dermal cells. We also discuss the advantages of the topical use of melatonin for therapeutic purposes and skin protection. In our view, endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin and its metabolites, represent two of the most potent defense systems against external damage to the skin.
Topics: Administration, Topical; Animals; Antioxidants; Humans; Melatonin; Metabolic Networks and Pathways; Oxidative Stress; Protective Agents; Skin
PubMed: 31597233
DOI: 10.3390/ijms20194948 -
Translational Psychiatry Jun 2021Melatonin is an ancient molecule that is evident in high concentrations in various tissues throughout the body. It can be separated into two pools; one of which is... (Review)
Review
Melatonin is an ancient molecule that is evident in high concentrations in various tissues throughout the body. It can be separated into two pools; one of which is synthesized by the pineal and can be found in blood, and the second by various tissues and is present in these tissues. Pineal melatonin levels display a circadian rhythm while tissue melatonin does not. For decades now, melatonin has been implicated in promoting and maintaining sleep. More recently, evidence indicates that it also plays an important role in neuroprotection. The beginning of our review will summarize this literature. As an amphiphilic, pleiotropic indoleamine, melatonin has both direct actions and receptor-mediated effects. For example, melatonin has established effects as an antioxidant and free radical scavenger both in vitro and in animal models. This is also evident in melatonin's prominent role in mitochondria, which is reviewed in the next section. Melatonin is synthesized in, taken up by, and concentrated in mitochondria, the powerhouse of the cell. Mitochondria are also the major source of reactive oxygen species as a byproduct of mitochondrial oxidative metabolism. The final section of our review summarizes melatonin's potential role in aging and psychiatric disorders. Pineal and tissue melatonin levels both decline with age. Pineal melatonin declines in individuals suffering from psychiatric disorders. Melatonin's ability to act as a neuroprotectant opens new avenues of exploration for the molecule as it may be a potential treatment for cases with neurodegenerative disease.
Topics: Aging; Animals; Antioxidants; Biomarkers; Cognition; Humans; Melatonin; Mental Disorders; Mitochondria; Neurodegenerative Diseases; Neuroprotection
PubMed: 34078880
DOI: 10.1038/s41398-021-01464-x -
European Review For Medical and... Jun 2023This review focuses on melatonin's role in advancing Parkinson's disease (PD) pathogenesis by inhibiting synaptic dysfunction and neuroinflammation. The early... (Review)
Review
This review focuses on melatonin's role in advancing Parkinson's disease (PD) pathogenesis by inhibiting synaptic dysfunction and neuroinflammation. The early pathological changes in PD, caused by SNCA/PARK1 and LRRK2/PARK8-mediated synaptic vesicle endocytosis during the early pathogenesis of PD, are briefly reviewed. The pathological changes related to synaptic plasticity and dendrites caused by synaptic dysfunction in neurotoxin 6-hydroxydopamine (6-OHDA) and 1-methl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced PD models are also discussed. The molecular mechanisms of pathological changes in PD, caused by the activation of microglia, astrocytes, and inflammatory vesicles, are discussed. The effectiveness of melatonin (MLT) in the restoration of dopaminergic neurons in the substantia nigra (SNc) has been established. MLT can upregulate dendritic numbers and restore synaptic plasticity by inhibiting alpha-synuclein aggregation and neurotoxicity. These functions of MLT improve sleep patterns in PD patients and suppresses synaptic dysfunction by inhibiting the overactivation of the PKA/CREB/BDNF signaling pathway and reactive oxygen species (ROS) production. MLT can maintain the typical transport and release of neurotransmitters. MLT also reduces neuroinflammation by promoting microglia 2 (M2) polarization, which reduces the expression of inflammatory cytokines. Additionally, MLT stimulates the activation of the retinoic acid receptor-related orphan receptor α (RORα) ligand and inhibits the activation of the Recombinant Sirtuin 1 (SIRT1)-dependent pathway, the NLR family pyridine structure domain 3 (NLRP3) inflammasome. By integrating the latest advances in synaptic dysfunction and neuroinflammation-related PD, researchers can develop clinical interventions for treating PD and further explore the pathological hallmarks of prodromal PD.
Topics: Humans; Animals; Mice; Parkinson Disease; Melatonin; NLR Family, Pyrin Domain-Containing 3 Protein; Neuroinflammatory Diseases; Inflammasomes; Dopaminergic Neurons; Disease Models, Animal; Mice, Inbred C57BL
PubMed: 37318481
DOI: 10.26355/eurrev_202306_32624