The structure and function of the epidermis is maintained by cell renewal based on epidermal turnover. Epidermal turnover is delayed by aging, and it is thought that the delay of the epidermal turnover is a cause of aging alternation of skin. The epidermal turnover is related to the energy metabolism of epidermal basal cells. Adenosine 5'-triphosphate (ATP) is needed for cell renewal: cell division, and adenosine 5'-monophosphate (AMP) increases the amount of intracellular ATP. These findings suggest that AMP accelerates the epidermal turnover delayed by aging. This study investigated whether AMP and adenosine 5'-monophosphate disodium salt (AMP2Na) accelerates the epidermal turnover. An effect of AMP2Na on cell proliferation was examined by our counting of keratinocytes. An effect of AMP2Na on cell cycle was examined by our counting of basal cells in DNA synthetic period of hairless rats. The effects of AMP2Na (or AMP) on the epidermal turnover were examined by our measuring stratum corneum transit time by use of guinea pigs, and by our measuring stratum corneum surface area by use of hairless rats and in a clinical pharmacological study. The AMP2Na showed two different profiles on the proliferation of primary cultured keratinocytes. At a low concentration it induced cell growth, whereas at a high concentration it inhibited cell growth. The number of basal cells in the DNA synthetic period of AMP2Na was significantly higher than that of the vehicle in hairless rats. The stratum corneum transit time of AMP2Na was significantly shorter than that of the vehicle in guinea pigs. The corneocyte surface area of emulsion containing AMP2Na was significantly smaller than that of the vehicle in volunteers. We conclude that AMP promotes the cell proliferation and the cell cycle progression of epidermal basal cells and accelerates epidermal turnover safely. In addition, AMP is useful for skin rejuvenation in dermatology and aesthetic dermatology.

Infrared‐A (IRA), which can penetrate deeply into the human skin, is a major component of solar radiation and is recognized to promote photoaging of human dermis. To our knowledge, however, the cellular and molecular consequences of human epidermis exposure to IRA have not been clarified. Thus, we investigated whether IRA inhibits the proliferation of normal human epidermal keratinocytes (NHEKs). IRA irradiation ed in cell cycle arrest at G1 and a dose‐dependent reduction in the proliferation of NHEKs. We found that mechanistic target of rapamycin complex 1 (mTORC1) was initially inactivated during IRA irradiation due to the formation of stress granules (SGs), and this inactivation was maintained for at least 6 h after irradiation due to Akt dephosphorylation. Furthermore, repeated exposure of human skin equivalents to IRA led to marked thinning of the epidermal cell layer. In conclusion, IRA irradiation inhibits mTORC1 activity possibly through two molecular mechanisms involving SG formation in the early‐phase and subsequent Akt dephosphorylation. This sequential mechanism seems to cause G1 cell cycle arrest and a reduction in cell proliferation, supporting the hypothesis that the decreased proliferation of basal keratinocytes that occurs during skin aging might be partly attributable to IRA radiation.

Abstract:Objective: In a preliminary study, we noted that citric acid has the potency to induce human beta defensins (hBD-2) in salivary secretions. As hBDs are thought to ameliorate periodontal disease by suppressing key periodontal pathogens we developed a citric acid-containing chewing gum (CA-gum) to test this hypothesis. Here we report, the effect of CA-gum on three major periodontal pathogens Prevotella intermedia (Pi), Tannerella forsythia (Tf), Treponema denticola (Td) and Fusobacterium species (Fb).Methods: A randomized, double-blind, placebo-controlled trial with 61 individuals, was conducted over 14 days. Each subject was allowed to chew CA-gum (31 subjects) or placebo gum (30 subjects) at irregular intervals, but was instructed to eat at least three pieces of gum a day. None had active caries, symptoms of gingivitis or periodontal disease, smoking history, or concurrent medication. To determine the levels of oral carriage of the putative pathogens, saliva was collected from each subject by paraffin chewing in a standard manner and, the number of total cultivative microorganisms (CFUs) determined. Five key periodontal pathogens, Pg, Pi, Tf, Td and Fb present in saliva were determined quantitatively using real-time polymerase chain reaction (PCR) (BML Inc., Saitama, JAPAN).Results: Compared with the placebo chewing gum group the CA-gum group had significantly lower levels of Prevotella intermedia, Tannerella forsythia, and Fusobacterium spp. in their saliva. (Wilcoxon t-test; p<0.01). However, chewing of either type of gum did not affect the salivary carriage of total cultivative bacteria (Wilcoxon t-test; p>0.05). Conclusion:Consumption of citric acid-laced chewing gum reduces significantly the burden of periodontal pathogens in saliva.