scholarly journals Autophagy in Human Skin Fibroblasts: Impact of Age

2018 ◽  
Vol 19 (8) ◽  
pp. 2254 ◽  
Author(s):  
Hei Kim ◽  
Seo-Yeon Park ◽  
Seok Moon ◽  
Jeong Lee ◽  
Sungjoo Kim
Keyword(s):  
Human Skin ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Autophagic Flux ◽  
Human Skin Fibroblasts ◽  
Waste Production ◽  
Lysosomal Proteolysis ◽  
Autophagic Activity ◽  
Cellular Components

Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin aging, we compared the autophagic activity of human skin fibroblasts between the young and old. According to TEM analyses, the number of autophagosomes per 1 μm2 cytoplasmic area was similar between young and aged fibroblasts. The amount of LC3 (microtubule-associated protein 1 light chain 3)-II, a form associated with autophagic vacuolar membranes, was also similar between the groups from Western blot analysis. Although residual bodies were more common in aged dermal fibroblasts, LC3 turnover and p62 assay showed little difference in the rate of lysosomal proteolysis between the young and old. RNA-seq analysis revealed that the major autophagy-modulating genes (BECN1, MAP1LC3B, ATG5, ATG7, ULK1, PIK3C3, mTOR) were not differentially expressed with age. Our results suggest that the basal autophagic flux in aged dermal fibroblasts is largely comparable to that of young fibroblasts. However, with a higher speed and amount of waste production in aged cells, we postulate that such autophagic flux may not be sufficient in keeping the old cells “clean”, resulting in skin aging. Aging is a complex process and, as such, the relationship between autophagy and aging is not straightforward. That is to say, autophagy does not simply decline with age. Regardless of the controversies on autophagic activity with age, autophagy plays a crucial role in counteracting aging, and strategies aimed at its modulation should hold promise for the prevention of skin aging.

scholarly journals miR-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1

2017 ◽  
Vol 8 (3) ◽  
pp. e2663-e2663 ◽  
Author(s):  
Hong-fu Xie ◽  
Ying-zi Liu ◽  
Rui Du ◽  
Ben Wang ◽  
Meng-ting Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Skin ◽  
Dna Methyltransferase ◽  
Skin Aging ◽  
Skin Fibroblasts ◽  
Luciferase Reporter ◽  
Dna Methyltransferase 1 ◽  
Human Skin Fibroblasts ◽  
Dnmt1 Expression ◽  
Methyltransferase 1

Abstract Skin aging is a complicated physiological process and epigenetic feature, including microRNA-mediated regulation and DNA methylation, have been shown to contribute to this process. DNA methylation is regulated by DNA methyltransferase, of which DNA methyltransferase 1 (DNMT1) is the most abundantly known. But evidence supporting its role in skin aging remains scarce, and no report regards its specifical upstream-regulating molecules in the process of skin aging so far. Here, we found that DNMT1 expression was markedly higher in young human skin fibroblasts (HSFs) than that in passage-aged HSFs, and DNMT1 knockdown significantly induced the senescence phenotype in young HSFs. We predicted the upstream miRNAs which could regulate DNMT1 with miRNA databases and found miR-377 had high homology with a sequence in the 3′-UTR of human DNMT1 mRNA. We confirmed that miR-377 was a potential regulator of DNMT1 by luciferase reporter assays. miR-377 expression in passage-aged HSFs was markedly higher than that in the young HSFs. miR-377 overexpression promoted senescence in young HSFs, and inhibition of miR-377 reduced senescence in passage-aged HSFs. Moreover, these functions were mediated by targeting DNMT1. Microfluidic PCR and next-generation bisulfite sequencing of 24 senescent-associated genes’ promoters revealed alterations of the promoter methylation levels of FoxD3, p53, and UTF1 in HSFs treated with miR-377 mimics or inhibitors. We also verified that the miR-377-mediated changes in p53 expression could be reversed by regulation of DNMT1 in HSFs. Similarly, there was a negative correlation between miR-377 and DNMT1 expression in young and photoaged HSFs, HSFs, or skin tissues from UV-unexposed areas of different aged donors. Our results highlight a novel role for miR-377-DNMT1-p53 axis in HSF senescence. These findings shed new light on the mechanisms of skin aging and identify future opportunities for its therapeutic prevention.

117-LB: Nonviral Direct Reprogramming of Human Skin Fibroblasts into Hormone-Expressing ß-Like Cell Clusters

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 117-LB
Author(s):  
LUKE R. LEMMERMAN ◽  
MARIA ANGELICA RINCON-BENAVIDES ◽  
SARAH A. TERSEY ◽  
BRITANI N. BLACKSTONE ◽  
HEATHER M. POWELL ◽  
...  
Keyword(s):  
Human Skin ◽  
Skin Fibroblasts ◽  
Direct Reprogramming ◽  
Human Skin Fibroblasts ◽  
Cell Clusters

Protective Effects of Green Tea Seed Extract against UVB-irradiated Human Skin Fibroblasts

2014 ◽  
Vol 43 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Ok Kyung Kim ◽  
Da-Eun Nam ◽  
Min-Jae Lee ◽  
Namgil Kang ◽  
Jae-Youn Lim ◽  
...  
Keyword(s):  
Human Skin ◽  
Green Tea ◽  
Seed Extract ◽  
Skin Fibroblasts ◽  
Protective Effects ◽  
Human Skin Fibroblasts

The intralysosomal pH in cultured human skin fibroblasts in relation to cystine accumulation in patients with cystinosis

1983 ◽  
Vol 116 (1) ◽  
pp. 154-161 ◽  
Author(s):  
Ronald P.J. Oude Elferink ◽  
Erik Harms ◽  
Anneke Strijland ◽  
Joseph M. Tager
Keyword(s):  
Human Skin ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts

The Effect of Practolol, In Vitro Generated Metabolites of Practolol and Chemical Analogues on the Rate of Growth of Human Skin Fibroblasts

1984 ◽  
Vol 12 (2) ◽  
pp. 89-97
Author(s):  
Graham R. Elliott ◽  
H.E. Amos ◽  
James W. Bridges
Keyword(s):  
Human Skin ◽  
Psoriasis Patient ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Cell Type ◽  
Normal Human Skin ◽  
Rate Of Growth ◽  
Structural Analogues ◽  
Normal Human

The rate of growth of normal human skin fibroblasts was inhibited in a dose related, reversible, fashion by practolol (N-4-(2-hydroxy)-3 (1-methyl)-aminopropoxyphenylacetamine) (ID50 1.35 ± 0.14 x 10-3M), propranolol (1-(isopropylamino)-3(1-naphthyl-oxy)-2-propranolol) (ID50 0.145 ± 0.02 x 10-3M) and paracetamol (N-(4-hydroxyphenyl) acetamide) (ID50 0.85 ± 0.2 x 10-3M). Skin fibroblasts isolated from a psoriasis patient were more sensitive towards practolol (ID50 0.48 ± 0.14 x 10-3M) and propranolol (ID50 0.032 ± 0.002 x 10-3M), but less sensitive towards paracetamol (ID50 1.3 ± 0.07 x 10-3M). In vitro generated metabolites of practolol, using normal or Arochlor 1254-pretreated hamster liver preparations, and structural analogues of practolol had no effect upon the growth of either cell type.

N-Methyl-L-Serine Stimulates Hyaluronan Production in Human Skin Fibroblasts

1999 ◽  
Vol 12 (5) ◽  
pp. 276-283 ◽  
Author(s):  
Shingo Sakai ◽  
Tetsuya Sayo ◽  
Shuji Kodama ◽  
Shintaro Inoue
Keyword(s):  
Human Skin ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts
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