Blocking negative effects of senescence in human skin fibroblasts with a plant extract

Abstract

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. 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). Here we identified an extract from the plant Solidago virgaurea subsp. 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. 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. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.

Extracellular Vesicles in Human Skin: Cross-Talk from Senescent Fibroblasts to Keratinocytes by miRNAs

“…dISF, dermal interstitial fluid; EV, extracellular vesicle; MVB, multivesicular bodies; NTA, nanoparticle tracking analysis; SEC, size exclusion chromatography; sEV, small extracellular vesicle; TEM, transmission electron microscopy; TFF, tangential flow filtration; WCL, whole cell lysate. senescence-associated secretory phenotype (EV-SASP) of fibroblasts (Terlecki-Zaniewicz et al, 2018), we aimed to test how these sEVs might alter the normal homeostasis of primary keratinocytes. Therefore, HDF were driven into stress-induced premature senescence (SIPS) by repetitive exposure to H 2 O 2 (Lämmermann et al, 2018;Terlecki-Zaniewicz et al, 2018).…”

“…senescence-associated secretory phenotype (EV-SASP) of fibroblasts (Terlecki-Zaniewicz et al, 2018), we aimed to test how these sEVs might alter the normal homeostasis of primary keratinocytes. Therefore, HDF were driven into stress-induced premature senescence (SIPS) by repetitive exposure to H 2 O 2 (Lämmermann et al, 2018;Terlecki-Zaniewicz et al, 2018). Induction of SIPS was confirmed by increased p21 levels (Supplementary Figure S2a), irreversible growth arrest (not shown), by a flattened and enlarged morphology (Supplementary Figure S2b), and by an increase in SA-ß-Gal activity (Supplementary Figure S2c and d).…”

“…Recently, EVs and their miRNA cargo emerged as communicators of the SASP of human dermal fibroblasts (EV-SASP; Terlecki-Zaniewicz et al, 2018;Urbanelli et al, 2016). In the skin, the presence of specific miRNAs within different layers and cell types regulates the balanced mRNA to miRNA ratio to maintain functional homeostasis (Botchkareva, 2012).…”

The Multicomponent, Multitarget Therapy SUC in Cats with Chronic Kidney Disease: A Multicenter, Prospective, Observational, Nonrandomized Cohort Study

“…This change in serum creatinine might indicate a dose-response relationship of SUC. On one hand, these findings might indicate that S. virgaurea slowed down tissue fibrosis as demonstrated in a fibroblast culture [30] to a certain extent if given at least twice weekly and that this protective effect might have been lost by underdosing SUC. On the other hand, it is possible that SUC might not have a long-term effect on the progressive course of CKD in cats.…”

“…vet. [30]. Furthermore, compounds isolated from S. virgaurea are reported to have antimicrobial, analgesic, anti-inflammatory, spasmolytic and mild diuretic activity [31].…”