About this Research Topic
Aging is a slow and continuous process of natural change associated with a wide range of deficits at the level of cell or body functions. According to the last report of the United Nations Department of Economic and Social Affairs in 2020, the world had 727 million aged people, over 65 years old, and this number is estimated to be doubled in 2050, where it would reach 1.5 billion. Efforts to discover the mechanism of aging, approaches to slow it down, or to treat the aging-related manifestations and abnormalities are amongst the hottest research topics nowadays. Recent reports are increasingly addressing the role of melatonin in the aging process. Melatonin is a hormone mainly released from the endocrine system's master gland, the pineal gland, in a circadian dependent manner. However, this hormone is also released circadian-independently by the choroid plexus in the central nervous system (CNS), the gastrointestinal tract, bone marrow cells, and others.
Although melatonin has not yet been approved by FDA, it is used to improve insomnia, jet lag disorders and as an FDA-approved dietary supplement. Numerous studies have investigated the role of melatonin in different diseases and abnormalities, either at the experimental or clinical levels. However, current studies on the role of melatonin in brain abnormalities are highly controversial. While melatonin is reported as a proliferative factor in different in vitro and in vivo experiments, such as Neural Stem Cells (NSCs) and human peripheral blood mononuclear cell (PBMC), some other studies reported the anti-proliferative and anti-tumor roles of melatonin in breast, prostate, melanoma, and colorectal cancers. Interestingly, the overall cancer incidence rate increases from 25 to 350, and 1,000 cases in ages below 20, from 45 to 49, and above 60 years old, respectively. In contrast, studies have shown that melatonin level decreases by aging. Therefore, one explanation for the increase of cancer incidence by aging is that melatonin reduction by aging eliminates its regulatory/inhibitory effect on cell proliferation, which could be considered a facilitating factor for carcinogenesis. However, since melatonin is a proliferative factor, then it is expected that its reduction by aging plays an anti-carcinogenesis role.
Most importantly, owing to the most advanced in vivo imaging techniques in freely behaving mice, it was recently shown that NSC’s proliferation in the subventricular zone (SVZ) considerably decreases at night, compared to day hours. Therefore, in vivo imaging of NSCs showed that melatonin plays an anti-proliferative role in adult mice. This observation is in favor of the first scenario and introduces melatonin as an antiproliferative factor. It is worth noting that melatonin is first synthesized by the Pineal gland and is then released into the third ventricle, where cerebrospinal fluid (CSF) is in close and direct contact with ependymal cilia of the SVZ. This further highlights the possibility that variations in melatonin release, here reduced by aging, quickly affects the physiology of SVZ NSCs. Elimination of this inhibitory/regulatory effect of melatonin on NSCs by aging causes them to be more proliferative. In accordance, there is an increasing number of reports of age-dependent incidence of glioblastoma, the most aggressive brain tumor, which is thought to be originating from NSCs in the SVZ.
The goal of this Research Topic is to collect high-quality Reviews and Original Research papers in the areas listed below with emphasis on melatonin’s roles and effects in aging as well as its implications in age-associated diseases. The scope of this Research Topic is to address questions including, but not limited, to:
• What is melatonin synthesis alterations, either from the pineal gland or other sources, in response to aging?
• What is the mechanistic pathway by which aging affects melatonin synthesis?
• How does aging affect the sleep quality by melatonin modulation?
• What is the therapeutical potential of melatonin in the treatment of CNS diseases (including Multiple Sclerosis, Alzheimer's Disease, Parkinson's Disease, etc.) or age-associated diseases?
• Does melatonin reduction by aging facilitate the glioblastoma occurrence or other kinds of cancers?
• Biology of melatonin in neurodegenerative disorders
• Molecular pathways in melatonin-related neurological diseases
• Implications of melatonin in neuroscience-related aging mechanisms
• Role of melatonin in aging
• Potential herbal source of melatonin for treating age-associated diseases.
• Night shift work, insomnia, and artificial light-at-night effects on the circadian rhythm of melatonin and their potential in accelerating the aging process.
Although melatonin has not yet been approved by FDA, it is used to improve insomnia, jet lag disorders and as an FDA-approved dietary supplement. Numerous studies have investigated the role of melatonin in different diseases and abnormalities, either at the experimental or clinical levels. However, current studies on the role of melatonin in brain abnormalities are highly controversial. While melatonin is reported as a proliferative factor in different in vitro and in vivo experiments, such as Neural Stem Cells (NSCs) and human peripheral blood mononuclear cell (PBMC), some other studies reported the anti-proliferative and anti-tumor roles of melatonin in breast, prostate, melanoma, and colorectal cancers. Interestingly, the overall cancer incidence rate increases from 25 to 350, and 1,000 cases in ages below 20, from 45 to 49, and above 60 years old, respectively. In contrast, studies have shown that melatonin level decreases by aging. Therefore, one explanation for the increase of cancer incidence by aging is that melatonin reduction by aging eliminates its regulatory/inhibitory effect on cell proliferation, which could be considered a facilitating factor for carcinogenesis. However, since melatonin is a proliferative factor, then it is expected that its reduction by aging plays an anti-carcinogenesis role.
Most importantly, owing to the most advanced in vivo imaging techniques in freely behaving mice, it was recently shown that NSC’s proliferation in the subventricular zone (SVZ) considerably decreases at night, compared to day hours. Therefore, in vivo imaging of NSCs showed that melatonin plays an anti-proliferative role in adult mice. This observation is in favor of the first scenario and introduces melatonin as an antiproliferative factor. It is worth noting that melatonin is first synthesized by the Pineal gland and is then released into the third ventricle, where cerebrospinal fluid (CSF) is in close and direct contact with ependymal cilia of the SVZ. This further highlights the possibility that variations in melatonin release, here reduced by aging, quickly affects the physiology of SVZ NSCs. Elimination of this inhibitory/regulatory effect of melatonin on NSCs by aging causes them to be more proliferative. In accordance, there is an increasing number of reports of age-dependent incidence of glioblastoma, the most aggressive brain tumor, which is thought to be originating from NSCs in the SVZ.
The goal of this Research Topic is to collect high-quality Reviews and Original Research papers in the areas listed below with emphasis on melatonin’s roles and effects in aging as well as its implications in age-associated diseases. The scope of this Research Topic is to address questions including, but not limited, to:
• What is melatonin synthesis alterations, either from the pineal gland or other sources, in response to aging?
• What is the mechanistic pathway by which aging affects melatonin synthesis?
• How does aging affect the sleep quality by melatonin modulation?
• What is the therapeutical potential of melatonin in the treatment of CNS diseases (including Multiple Sclerosis, Alzheimer's Disease, Parkinson's Disease, etc.) or age-associated diseases?
• Does melatonin reduction by aging facilitate the glioblastoma occurrence or other kinds of cancers?
• Biology of melatonin in neurodegenerative disorders
• Molecular pathways in melatonin-related neurological diseases
• Implications of melatonin in neuroscience-related aging mechanisms
• Role of melatonin in aging
• Potential herbal source of melatonin for treating age-associated diseases.
• Night shift work, insomnia, and artificial light-at-night effects on the circadian rhythm of melatonin and their potential in accelerating the aging process.
Keywords: melatonin, aging, synthesis, pineal gland, neurodegeneration
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