15, 16 We suggest to term this process “papillary to reticular transition” (PRT). ![]() 15, 16 When aged in vitro or in vivo, changes in cell characteristics are almost exclusively seen in papillary fibroblasts, which led to the hypothesis that the age-related atrophy in the papillary dermis of human skin might involve a gradual de- or trans-differentiation process of the papillary to the reticular phenotype. 11 They also differ in the production of ECM and growth factors, 11, 12 their response to growth factors and epidermal signalling 13, 14 and only papillary fibroblasts seem to be able to support the formation of a fully differentiated human skin equivalent (HSE). Fibroblasts isolated from the papillary dermis have a lean spindle-like morphology, a higher proliferative capacity and a lower sensitivity towards contact inhibition than their flat and irregular-shaped reticular counterparts. The dermis of human skin can be divided into two distinct layers, the upper papillary dermis and the lower reticular dermis. One of the first organs where senescent cells have been identified in vivo, is the skin, 8 which contains between 20% 9 and 60% 10 of senescent fibroblasts. 4, 5, 6 Senescent cells are irreversibly cell-cycle arrested via the p53–p21 CIP1 or the p16 INK4a–Rb axis, accumulate senescence-associated β-galactosidase activity (SA-β-gal) and display a typical morphology. This consists of pro-inflammatory cytokines and chemokines, extracellular matrix (ECM) remodelling proteases and growth factors and results in a vicious cycle of progressive functional loss in tissues and organs. 1, 2 While transiently present senescent cells have beneficial functions in wound healing, 3 their chronic persistence and accumulation with age negatively affects the surrounding tissue by the senescence-associated secretory phenotype (SASP). ![]() Senescent cells accumulate in vivo and their selective elimination increases the healthspan of mice. Similar content being viewed by othersĬellular senescence is involved in the development of age-related diseases and the loss of tissue functionality with age. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality. ![]() When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. alpestris, which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. Here we identified an extract from the plant Solidago virgaurea subsp. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice.
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