Kento Takaya

Dermal fibroblasts maintain the skin homeostasis by interacting with the epidermis and extracellular matrix. Their senescence contributes to functional defects in the skin related to aging. Therefore, there is an urgent need for novel therapeutic agents that could inhibit fibroblast senescence. In this study, we investigated the effects of <i>Cistanche deserticola</i> polysaccharide (CDP), a natural anti-inflammatory component, on the progression of senescence in human dermal fibroblasts. Normal

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will provide clues for achieving scarless wound healing. The fibroblast growth factor (FGF) family is a key regulator of inflammation and fibrosis during wound healing. We aimed to determine the expression an

Senescent cells accumulate in aging skin, causing age-related changes and a decline in functional efficiency. Therefore, senolysis, a treatment that specifically removes senescent cells and rejuvenates the skin, should be explored. We targeted apolipoprotein D (ApoD), a previously identified marker expressed on senescent dermal fibroblasts, and investigated a novel senolysis approach using a monoclonal antibody against this antigen and a secondary antibody conjugated with the cytotoxic drug pyrr

Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. To elucidate the function of senescent cells in skin aging, we evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin. Here, primary human dermal fibroblasts (HDFs) were ind

Cellular senescence is characterized by cell cycle arrest and the senescence-associated secretory phenotype (SASP) and can be triggered by a variety of stimuli, including deoxyribonucleic acid (DNA) damage, oxidative stress, and telomere exhaustion. Cellular senescence is associated with skin aging, and identification of specific markers of senescent cells is essential for development of targeted therapies. Cathepsin F (CTSF) has been implicated in dermatitis and various cancers and participates

Up to a certain developmental stage, a fetus can completely regenerate wounds in the skin. To clarify the mechanism of fetal skin regeneration, identifying when the skin switches from fetal-type wound regeneration to adult-type wound repair is necessary. We hypothesized that this switch occurs at several time points and that complete skin regeneration requires epidermal-dermal interactions and the formation of actin cables. We compared normal skin and wound morphology at each developmental stage

Chronic senescence, such as aging, contributes to age-related tissue dysfunction and disease development. The accumulation of senescent fibroblasts and the senescence-associated secretory phenotype is particularly implicated in this process. Removal of senescent cells has been reported to prevent tissue dysfunction and to extend the life span during aging. ABT-263 (navitoclax), which inhibits antiapoptotic proteins, is a leading antiaging drug; however, its role in human skin aging is unclear. T

There is growing evidence that the appearance and texture of the skin that is altered during the aging process are considerably enhanced by the accumulation of senescent dermal fibroblasts. These senescent cells magnify aging via an inflammatory, histolytic, and senescence-associated secretory phenotype (SASP). Secreted frizzled-related protein 4 (SFRP4) was previously determined to be expressed in dermal fibroblasts of aging skin, and its increased expression has been shown to promote cellular

The current understanding of skin aging is that senescent fibroblasts accumulate within the dermis and subcutaneous fat to cause abnormal tissue remodeling and extracellular matrix dysfunction, triggering a senescence-associated secretory phenotype (SASP). A novel therapeutic approach to prevent skin aging is to specifically eliminate senescent dermal fibroblasts; this requires the identification of specific protein markers for senescent cells. Apolipoprotein D (ApoD) is involved in lipid metabo

Skin senescence is characterized by a decrease in extracellular matrix and the accumulation of senescent fibroblasts in the dermis, and their secretion of humoral factors. Ependymin-related protein 1 (EPDR1) is involved in abnormal fibroblast metabolism and collagen deposition, however, its relation to skin aging is unclear. We investigated whether and how EPDR1 is involved in age-related dermal deterioration. When young dermal fibroblasts and senescent cells were co-cultured in a semipermeable

The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens that are specifically expressed on senescent cells for their selective elimination. We showed that atypical chemokine receptor 3 (ACKR3), a receptor of the CXC motif chemokine 12 (CXCL12) impl

Senescent cells accumulate with age and contribute to age-related diseases and organ dysfunctions. Early evidence suggests that removal of senescent cells using senolytic drugs improves the aging phenotype in mice and may improve the health of individuals with chronic diseases. Signs of skin aging, including wrinkles, and sagging, occur largely due to the accumulation of senescent fibroblasts within the dermis; However, there is currently no skin treatment that eliminates senescent cells. In thi