Autophagy Declines with Premature Skin Aging resulting in Dynamic Alterations in Skin Pigmentation and Epidermal Differentiation.

Autophagy is a membrane traffic system that provides sustainable degradation of cellular components for homeostasis, and is thus considered to promote health and longevity, though its activity declines with aging. The present findings show deterioration of autophagy in association with premature skin aging. Autophagy flux was successfully determined in skin tissues, which demonstrated significantly decreased autophagy in hyperpigmented skin such as that seen in senile lentigo.

The Surprising Effect of Phenformin on Cutaneous Darkening and Characterization of Its Underlying Mechanism by a Forward Chemical Genetics Approach.

Melanin in the epidermis is known to ultimately regulate human skin pigmentation. Recently, we exploited a phenotypic-based screening system composed of ex vivo human skin cultures to search for effective materials to regulate skin pigmentation. Since a previous study reported the potent inhibitory effect of metformin on melanogenesis, we evaluated several biguanide compounds.

Perilla extract improves frequent urination in spontaneously hypertensive rats with enhancement of the urothelial presence and anti-inflammatory effects.

Objective: To investigate the effects of perilla extract on urinary symptoms in spontaneously hypertensive rats as a model of spontaneous overactive bladder.

Methods: Spontaneously hypertensive rats were randomly divided into two groups and fed either a control diet or a perilla extract-containing diet. Cystometry, gene expression and histological analyses were carried out to evaluate the effects of perilla extract after 2-week feeding of either the control or the perilla extract diet.

Identification of a Novel TRPM8 Agonist from Nutmeg: A Promising Cooling Compound.

The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary receptor for innocuous cold stimuli (<28 °C) in humans. TRPM8 agonists such as -(-)-menthol are widely used as flavors and additives to impart briskness, in addition to medicinal uses for inflammation and pain. Though various natural and synthetic agonists have been explored, only few natural compounds are known.

Alteration of amiloride-sensitive salt taste nerve responses in aldosterone/NaCl-induced hypertensive rats.

Salt taste sensitivity is related to physiological condition, and declined in hypertensive patients. However, little is known about the mechanism underlying changes in salt taste sensitivity during the development of hypertension. This is largely due to lack of an appropriate animal model which shows the decline of salt taste sensitivity caused by hypertension.

Cooperation of endothelin-1 signaling with melanosomes plays a role in developing and/or maintaining human skin hyperpigmentation.

Skin hyperpigmentation is characterized by increased melanin synthesis and deposition that can cause significant psychosocial and psychological distress. Although several cytokine-receptor signaling cascades contribute to the formation of ultraviolet B-induced cutaneous hyperpigmentation, their possible involvement in other types of skin hyperpigmentation has never been clearly addressed. Since our continuous studies using skin specimens from more than 30 subjects with ethnic skin diversity emphasized a consistent augmentation in the expression of endothelin-1 (ET-1) and its receptor (Endothelin B receptor, ET-B) in hyperpigmented lesions, including senile lentigos (SLs), the precise function of ET-1 signaling was investigated in the present study.

The inhibitory effect of a Platycodon root extract on ultraviolet B-induced pigmentation due to a decrease in Kit expression.

The signaling of stem cell factor (SCF) through its receptor Kit is known to play an important role in regulating cutaneous melanogenesis. In the course of UVB-induced pigmentation, the expression of membrane-bound SCF by epidermal keratinocytes is upregulated at an early phase and subsequently activates neighboring melanocytes via their Kit receptors. In order to identify effective skin-lightening materials, we screened botanical extracts to determine their abilities to diminish Kit expression in melanocytes.

Essential role of RAB27A in determining constitutive human skin color.

Human skin color is predominantly determined by melanin produced in melanosomes within melanocytes and subsequently distributed to keratinocytes. There are many studies that have proposed mechanisms underlying ethnic skin color variations, whereas the processes involved from melanin synthesis in melanocytes to the transfer of melanosomes to keratinocytes are common among humans. Apart from the activities in the melanogenic rate-limiting enzyme, tyrosinase, in melanocytes and the amounts and distribution patterns of melanosomes in keratinocytes, the abilities of the actin-associated factors in charge of melanosome transport within melanocytes also regulate pigmentation.

An investigator blinded cross-over study to characterize the cutaneous effects and suitability of modern sanitary pads for menstrual protection for women residing in the USA.

Background: The cutaneous and sensory effects of the practical usage of sanitary pads have been studied globally. However, clinical studies in the United States were conducted only quite a long time ago, and the results of these studies were not published.

Methods: Fifty-four women residing in the United States were asked to use commercially available sanitary pads with a nonwoven unique surface sheet and pads with a perforated film.

Involvement of IGF-1/IGFBP-3 signaling on the conspicuousness of facial pores.

Conspicuous facial pores are one type of serious esthetic defects for many women. We previously reported that the severity of impairment of skin architecture around facial pores correlates well with the appearance of facial pores in several ethnic groups. In our last report, we showed that serum levels of insulin-like growth factor-1 (IGF-1) correlate well with facial pore size and with the severity of impairment of epidermal architecture around facial pores.

Stem cell factor-KIT signalling plays a pivotal role in regulating pigmentation in mammalian hair.

Hair greying is one of the most distinct but least comprehended features of senescence. The signalling of stem cell factor (SCF) and its receptor KIT has been documented to regulate essential roles in the maintenance of embryonic melanocyte lineages and postnatal cutaneous melanogenesis, although little is known about its detailed mechanisms in postnatal hair pigmentation. To address this, anagen human hair follicles and C57BL/6 murine pelage were analysed in this study.

Mechanistic effects of long-term ultraviolet B irradiation induce epidermal and dermal changes in human skin xenografts.

UVB irradiation has been reported to induce photoaging and suppress systemic immune function that could lead to photocarcinogenesis. However, because of the paucity of an UVB-induced photodamaged skin model, precise and temporal mechanism(s) underlying the deleterious effects of long-term UVB exposure on human skin have yet to be delineated. In this study, we established a model using human skin xenografted onto severe combined immunodeficient mice, which were subsequently challenged by repeated UVB irradiation for 6 weeks.

The essential role of p53 in hyperpigmentation of the skin via regulation of paracrine melanogenic cytokine receptor signaling.

Hyperpigmentation of the skin is characterized by increases in melanin synthesis and deposition. Although considered a significant psychosocial distress, little is known about the detailed mechanisms of hyperpigmentation. Recently, the tumor suppressor protein p53 has been demonstrated to promote ultraviolet B-induced skin pigmentation by stimulating the transcription of a melanogenic cytokine, POMC (pro-opiomelanocortin), in keratinocytes.

Ethnic differences in the structural properties of facial skin.

Background: Conspicuous facial pores are one type of serious aesthetic defects for many women. However, the mechanism(s) that underlie the conspicuousness of facial pores remains unclear. We previously characterized the epidermal architecture around facial pores that correlated with the appearance of those pores.

Production of the soluble form of KIT, s-KIT, abolishes stem cell factor-induced melanogenesis in human melanocytes.

The signaling of stem cell factor (SCF) and its receptor KIT (membrane-bound KIT; m-KIT) plays an important role in melanocyte development, survival, proliferation, and melanogenesis. It has been demonstrated in other systems that a soluble form of m-KIT released from the cell surface (s-KIT) regulates SCF signaling, although there have been no reports pertaining to the existence and the biological role of s-KIT in melanocytes. In this study, we therefore examined the involvement of s-KIT in melanogenesis.

The characteristics of aromatase deficient hairless mice indicate important roles of extragonadal estrogen in the skin.

The roles of extragonadal estrogen in the skin are poorly understood, due to the lack of proper animal models. We examined the skin phenotypes of aromatase-knockout hairless (ArKO) mice and wild-type hairless (WT) mice, both of which were obtained through crossbreeding of Ar+/- mice and hairless mice. Differences in the skins of ArKO and WT mice were compared with those of ovariectomized (OVX) and control (Sham) mice.

Comparison of age-related changes in facial wrinkles and sagging in the skin of Japanese, Chinese and Thai women.

Background: Differences in skin aging features between Asians and Caucasians are commonly known, whereas little is known about such differences in various Asian populations.

Objective: A survey was carried out in Tokyo, Shanghai and Bangkok to identify specific features of skin aging in each population and to evaluate whether our conventional photo scale is an appropriate tool for this type of comparative study.

Methods: Eighty-seven women residing in Tokyo, 100 women residing in Shanghai, and 90 women residing in Bangkok were examined by a specialist.

Functional analysis of keratinocytes in skin color using a human skin substitute model composed of cells derived from different skin pigmentation types.

Skin color is one of the most distinct features in the human race. To assess the mechanisms of skin color variation, human skin substitutes (HSS) were constructed by grafting mixtures of cultured keratinocytes and melanocytes from a combination of donor skin types, together with light skin derived fibroblasts, into chambers inserted onto the back skin of severe combined immunodeficient (SCID) mice. The resulting complexion coloration of the HSS was relatively darker and lighter when dark and light skin derived keratinocytes, respectively, were combined with melanocytes derived from either light or dark skin.

Interaction between stem cell factor and endothelin-1: effects on melanogenesis in human skin xenografts.

The two paracrine melanogenic cytokines, stem cell factor (SCF) and endothelin-1 (ET-1), have been demonstrated to play pivotal roles in skin pigmentation including UVB-induced pigmentation and senile lentigo. However, little is known regarding their interactive effect on skin pigmentation. In order to investigate their roles in vivo, facultative pigmentation of human skin xenografts on severe combined immunodeficient (SCID) mice was assessed.

Inhibitory mechanism of an extract of Althaea officinalis L. on endothelin-1-induced melanocyte activation.

It is known that expression of endothelin-1 (ET-1) increases in the epidermis after UVB irradiation, and that this plays an important role during the induction of pigmentation both as a mitogen and as a melanogen for normal human melanocytes (NHMC). When ET-1 acts on NHMC via the endothelin B receptor (ET(B)R) on their cell surface, mobilization of intracellular calcium is induced, which is followed by activation of Raf-1 located upstream of mitogen activated protein kinase (MAPK). We have continued the search for new agent which inhibit this calcium mobilization and we have found that an extract of Althaea officinalis L.