Circadian rhythms, ≈24 h oscillations in behavior and physiology, are reflected in all cells of the body and function to optimize cellular functions and meet environmental challenges associated with the solar day. This multi-oscillatory network is entrained by the master pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which directs an organism’s rhythmic expression of physiological functions and behavior via a hierarchical system. This system has been highly conserved throughout evolution and uses transcriptional–translational autoregulatory loops. This master clock, following environmental cues, regulates an organism’s sleep pattern, body temperature, cardiac activity and blood pressure, hormone secretion, oxygen consumption and metabolic rate. Mammalian peripheral clocks and clock gene expression have recently been discovered and are present in all nucleated cells in our body. Like other essential organ of the body, the skin also has cycles that are informed by this master regulator. In addition, skin cells have peripheral clocks that can function autonomously. First described in 2000 for skin, this review summarizes some important aspects of a rapidly growing body of research in circadian and ultradian (an oscillation that repeats multiple times during a 24 h period) cutaneous rhythms, including clock mechanisms, functional manifestations, and stimuli that entrain or disrupt normal cycling. Some specific relationships between disrupted clock signaling and consequences to skin health are discussed in more depth in the other invited articles in this IJMS issue on Sleep, Circadian Rhythm and Skin.

Overproduction of sebum, especially during adolescence, is causally related to acne and inflammation. As a way to reduce sebum and its interference with the process of follicular keratinization in the pilosebaceous unit leading to inflammatory acne lesions, antihistamines were investigated for their effect on sebocytes, the major cell of the sebaceous gland responsible for producing sebum. Reverse transcriptase-PCR analysis and immunofluorescence of an immortalized sebocyte cell line (SZ95) revealed the presence of histamine-1 receptor (H-1 receptor), and thus indicated that histamines and, conversely, antihistamines could potentially modulate sebocyte function directly. When sebocytes were incubated with an H-1 receptor antagonist, diphenhydramine (DPH), at non-cytotoxic doses, a significant decrease in squalene levels, a biomarker for sebum, was observed. As determined by high-performance liquid chromatography, untreated sebocytes contained 6.27 (±0.73) nmol squalene per 10⁶ cells, whereas for DPH-treated cells, the levels were 2.37 (±0.24) and 2.03 (±0.97) nmol squalene per 10⁶ cells at 50 and 100 μM, respectively. These data were further substantiated by the identification of histamine receptors in human sebaceous glands. In conclusion, our data show the presence of histamine receptors on sebocytes, demonstrate how an antagonist to these receptors modulated cellular function, and may indicate a new paradigm for acne therapy involving an H-1 receptor-mediated pathway.

Cigarette smoke, whether indirect or direct stream, is an environmental pollutant which presents an increasing health problem. In order to determine damage to human skin at the biochemical level, volar forearms were exposed to cigarette smoke for fifteen minutes and then assayed for the presence of stratum corneum lipid peroxides. A time-dependent increase was observed over a 24-hour post-exposure period. At 24 h, the average baseline level of lipid peroxides was 14.9 nmol/unit area of skin as compared to 32.0 nmol/unit area of skin for the smoke-exposed arms. In addition, when topical antioxidants were pre-applied to the skin and then exposed to cigarette smoke, an average decrease of 40.9% in lipid peroxide values was observed. These data demonstrate that peroxidation was induced in human skin by cigarette smoke and subsequently inhibited by the presence of antioxidants.