Protective Role of Melatonin and Its Metabolites in Skin Aging

Bocheva, Georgeta; Slominski, Radomir M.; Janjetovic, Zorica; Kim, Tae Kang; Böhm, Markus; Steinbrink, Kerstin; Reíter, Russel J.; Kleszczyński, Konrad; Slominski, Andrzej

doi:10.3390/ijms23031238

Cited by 75 publications

(94 citation statements)

References 284 publications

(417 reference statements)

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“…Considering melatonin's ability to upregulate SIRT1 expression 10 (see Section 5.4), intracutaneously produced melatonin may thus positively regulate autophagy and exert antiaging properties by stabilizing SIRT1 levels. The role of melatonin in skin aging has been recently extensively reviewed 238 …”

Section: Melatonin Oxidative Stress and The Melanocyte Ecosystemmentioning

confidence: 99%

Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective

Sevilla

Chéret

Slominski

et al. 2022

Journal of Pineal Research

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The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms of action, which include the regulation of vertebrate pigmentation. Although first discovered through its potent skin‐lightening effects in amphibians, melatonin's role in human skin and hair follicle pigmentation and its impact on melanocyte physiology remain unclear. Synthesizing our limited current understanding of this role, we specifically examine its impact on melanogenesis, oxidative biology, mitochondrial function, melanocyte senescence, and pigmentation‐related clock gene activity, with emphasis on human skin, yet without ignoring instructive pointers from nonhuman species. Given the strict dependence of melanocyte functions on the epithelial microenvironment, we underscore that melanocyte responses to melatonin are best interrogated in a physiological tissue context. Current evidence suggests that melatonin and some of its metabolites inhibit both, melanogenesis (via reducing tyrosinase activity) and melanocyte proliferation by stimulating melatonin membrane receptors (MT1, MT2). We discuss whether putative melanogenesis‐inhibitory effects of melatonin may occur via activation of Nrf2‐mediated PI3K/AKT signaling, estrogen receptor‐mediated and/or melanocortin‐1 receptor‐ and cAMP‐dependent signaling, and/or via melatonin‐regulated changes in peripheral clock genes that regulate human melanogenesis, namely Bmal1 and Per1. Melatonin and its metabolites also accumulate in melanocytes where they exert net cyto‐ and senescence‐protective as well as antioxidative effects by operating as free radical scavengers, stimulating the synthesis and activity of ROS scavenging enzymes and other antioxidants, promoting DNA repair, and enhancing mitochondrial function. We argue that it is clinically and biologically important to definitively clarify whether melanocyte cell culture‐based observations translate into melatonin‐induced pigmentary changes in a physiological tissue context, that is, in human epidermis and hair follicles ex vivo, and are confirmed by clinical trial results. After defining major open questions in this field, we close by suggesting how to begin answering them in clinically relevant, currently available preclinical in situ research models.

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Section: Melatonin Oxidative Stress and The Melanocyte Ecosystemmentioning

confidence: 99%

Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective

Sevilla

Chéret

Slominski

et al. 2022

Journal of Pineal Research

Self Cite

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“…Intrinsic skin aging occurs naturally with chronological aging, which is mainly influenced by genetic predisposition, neuroendocrinology, and metabolic factors acting in an age-dependent manner, and it also can be accelerated by external environment factors such as ultraviolet radiation (UVR), environmental pollutants, smoking, low quality nutrition, and microbial infections 2-6 . However, skin has the ability to protect itself from various external stressors through the neuroendocrine systems by producing several protective molecules, including vitamin D and melatonin [7][8][9][10][11] . Both intrinsic and extrinsic skin aging induce the breakdown of extracellular matrix (ECM) proteins in the skin, resulting in decreased skin elasticity and tension.…”

mentioning

confidence: 99%

Human placental extract activates a wide array of gene expressions related to skin functions

Chang¹,

Chin²,

Kimura³

et al. 2022

Sci Rep

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As skin aging is one of the most common dermatological concerns in recent years, scientific research has promoted treatment strategies aimed at preventing or reversing skin aging. Breakdown of the extracellular matrix (ECM), such as collagen and elastin fibers, in the skin results in decreased skin elasticity and tension. Cutaneous cells, especially fibroblasts in the dermis layer of the skin, mainly produce ECM proteins. Although clinical studies have demonstrated that placental extract (PE) has positive effects on skin health, the molecular mechanisms by which PE acts against skin aging are still largely unknown. In this study, we performed RNA-sequence analysis to investigate whether human PE (HPE) alters ECM-related gene expression in normal human dermal fibroblast (NHDF) cells. Gene ontology analysis showed that genes related to extracellular matrix/structure organization, such as COL1A1, COL5A3, ELN, and HAS2 were highly enriched, and most of these genes were upregulated. We further confirmed that the HPE increased the type I collagen, proteoglycan versican, elastin, and hyaluronan levels in NHDF cells. Our results demonstrate that HPE activates global ECM-related gene expression in NHDF cells, which accounts for the clinical evidence that the HPE affects skin aging.

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“…Melatonin possesses broad-spectrum activity, as it synchronizes the circadian rhythm, regulates energy metabolism and the ageing process, attenuates blood-brain barrier (BBB) impairment, and modulates the neuroinflammatory response and oxidative stress in the brain and peripheral tissues [14,15,26,[29][30][31][32][33][34]. Melatonin also affects the peripheral nervous system.…”

Section: Melatoninmentioning

confidence: 99%

Melatonin and the Brain–Heart Crosstalk in Neurocritically Ill Patients—From Molecular Action to Clinical Practice

Bekała

Płotek

Siwicka-Gieroba

et al. 2022

IJMS

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Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain–heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.

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Protective Role of Melatonin and Its Metabolites in Skin Aging

Cited by 75 publications

References 284 publications

Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective

Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective

Human placental extract activates a wide array of gene expressions related to skin functions

Melatonin and the Brain–Heart Crosstalk in Neurocritically Ill Patients—From Molecular Action to Clinical Practice

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