Age Associated Decrease of MT-1 Melatonin Receptor in Human Dermal Skin Fibroblasts Impairs Protection Against...

Area of Science:

• Chronobiology
• Dermatology
• Molecular Biology

Background:

• The human body possesses internal circadian rhythms synchronized with the day/night cycle.
• Skin cells also exhibit autonomous clocks, with melatonin playing a role in regulating bodily functions.
• Melatonin is present in the skin and influences clock gene expression.

Purpose of the Study:

• To investigate the effect of melatonin on clock gene expression in human skin cells.
• To evaluate the role of the MT-1 melatonin receptor in mediating melatonin's effects on skin.
• To determine the impact of aging on MT-1 receptor levels and skin cell protection.

Main Methods:

• Dose-dependent stimulation of PER1 clock gene expression by melatonin.
• Analysis of MT-1 receptor expression in fibroblasts from young and old subjects using immunocytochemistry, Western blotting, and RT-PCR.
• siRNA-mediated knockdown of MT-1 receptor to assess its role in UV-induced oxidative stress and DNA damage.

Main Results:

• Melatonin dose-dependently stimulated PER1 clock gene expression in dermal fibroblasts and epidermal keratinocytes.
• MT-1 receptor expression was confirmed in human skin fibroblasts, with a significant age-dependent decrease observed in mature cells.
• MT-1 receptor knockdown enhanced UV-induced oxidative stress (H2O2 production) and increased DNA damage in skin cells.

Conclusions:

• The melatonin pathway is crucial for skin aging and damage prevention.
• The MT-1 melatonin receptor plays a protective role against UV-induced DNA damage in skin.
• Modulating melatonin receptors in skin offers potential strategies for decelerating skin aging and is linked to skin circadian rhythm.