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Published on: September 7, 2013
Age Associated Decrease of MT-1 Melatonin Receptor in Human Dermal Skin Fibroblasts Impairs Protection Against
Kelly Dong1, Earl Goyarts1, Antonella Rella1
1Skin Biology & BioActives, R&D, Estée Lauder Companies, Melville, NY 11747, USA.
Abstract:
The human body follows a physiological rhythm in response to the day/night cycle which is synchronized with the circadian rhythm through internal clocks. Most cells in the human body, including skin cells, express autonomous clocks and the genes responsible for running those clocks. Melatonin, a ubiquitous small molecular weight hormone, is critical in regulating the sleep cycle and other functions in the body. Melatonin is present in the skin and, in this study, we showed that it has the ability to dose-dependently stimulate PER1 clock gene expression in normal human dermal fibroblasts and normal human epidermal keratinocytes. Then we further evaluated the role of MT-1 melatonin receptor in mediating melatonin actions on human skin using fibroblasts derived from young and old subjects. Using immunocytochemistry, Western blotting and RT-PCR, we confirmed the expression of MT-1 receptor in human skin fibroblasts and demonstrated a dramatic age-dependent decrease in its level in mature fibroblasts. We used siRNA technology to transiently knockdown MT-1 receptor in fibroblasts. In these MT-1 knockdown cells, UV-dependent oxidative stress (H2O2 production) was enhanced and DNA damage was also increased, suggesting a critical role of MT-1 receptor in protecting skin cells from UV-induced DNA damage. These studies demonstrate that the melatonin pathway plays a pivotal role in skin aging and damage. Moreover, its correlation with skin circadian rhythm may offer new approaches for decelerating skin aging by modulating the expression of melatonin receptors in human skin.
Insights
Melatonin stimulates skin clock gene expression and protects against UV damage. Its receptor, MT-1, declines with age, increasing skin aging and DNA damage risk.
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.
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