Melatonin finely tunes proliferation and senescence in hematopoietic stem cells.

The circadian clock refers to the intrinsic biological rhythms of physiological functions and behaviours. It synergises with the solar cycle and has profound effects on normal metabolism and organismal fitness. Recent studies have suggested that the circadian clock exerts great influence on the differentiation of stem cells. Here, we focus on the close relationship between the circadian clock and mesenchymal stem cell fate decisions in the skeletal system. The underlying mechanisms include hormone signals and the activation and repression of different transcription factors under circadian regulation. Additionally, the clock interacts with epigenetic modifiers and non-coding RNAs and is even involved in chromatin remodelling. Although the specificity and safety of circadian therapy need to be further studied, the circadian regulation of stem cells can be regarded as a promising candidate for health improvement and disease prevention. 

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The circadian clock has roles in mesenchymal stem cell fate decision

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The role of melatonin in bone regeneration: A review of involved signaling pathways.

AbstractMammalian cells have multifaceted systems and structures to avoid accumulation of unfolded or misfolded proteins, the accumulation of which is a feature of aging and aging-related conditions. With a gradually increasing elderly population, aging-related pathologies such as neurodegenerative disorders, cancer, and cardiovascular diseases are becoming a growing economic, social, and personal problem. Few or no effective treatments are presented for aging-associated neurodegenerative conditions, which progress in an irreversible way.Melatonin (MLT), a pineal hormone and an endogenous antioxidant, has numerous physiological functions in the brain, including regulating circadian rhythms, scavenging free radicals, preventing oxidation, and suppressing neuroinflammation. Clinical studies revealed that MLT levels are significantly reduced in patients with neurodegenerative diseases. Research proved that MLT prevents activity on neurodegeneration. As a chronobiotic, MLT can modify circadian rhythm. As a cytoprotective molecule, it prevents inflammatory injury in neurodegenerative diseases and aging.This chapter discusses neurodegenerative diseases, which are the main risk elements of aging, antioxidant properties, and action of MLT, as well as MLT achievement in the pathogenesis of neurodegenerative diseases and its associations with the nine biological hallmarks of aging. The main physiological mechanisms of aging and their potential as targets of novel treatments for neurodegenerative diseases are also discussed.KeywordsMelatoninAgingOxidative stressNeurodegenerative diseasesCancer 

Melatonin in Aging and Aging-Related Disorders

Melatonin is a hormone, synthesized in the pineal gland, which primarily controls the circadian rhythm of the body. In recent years, melatonin has also been shown to regulate metabolism, provide neuroprotection, and act as an anti-inflammatory, free radical scavenger. There has also been a recent research interest in the role of melatonin in regulating mesenchymal stromal cells (MSCs). MSCs are pivotal for their ability to differentiate into a variety of different tissues. There is also increasing evidence for the therapeutic prospects of MSCs via paracrine signaling. In addition to secreting cytokines and chemokines, MSCs can secrete extracellular vesicles (EVs), allowing them to respond to injury and promote tissue regeneration. While there has been a major research interest in the use of MSCs for regenerative medicine, the clinical application is limited by many risks, including tumorigenicity, senescence, and sensitivity to toxic environments. The use of MSC-derived EVs for cell-free therapy can potentially avoid the disadvantages of MSCs, which makes this an exciting prospect for regenerative medicine. Prior research has shown that MSCs, via paracrine mechanisms, can identify receptor-independent responses to melatonin and then activate a series of downstream pathways, which exert a variety of effects, including anti-tumor and anti-inflammatory effects. Here we review the synthesis of melatonin, its mechanisms of action, and the effect of melatonin on MSCs via paracrine signaling. Furthermore, we summarize the current clinical applications of melatonin and discuss future prospects.

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Shu-De Yang

Papers

Effect of Melatonin for Regulating Mesenchymal Stromal Cells and Derived Extracellular Vesicles.