Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes

In this study, we determined the molecular mechanism ofγ-tocotrienol (GTT) in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs). Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associatedβ-galactosidase (SAβ-gal) and promoted G0/G1cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity. Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochromecrelease and increased activation of caspase-9 and caspase-3 (P<0.05). GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochromecrelease and decreased activation of caspase-9 and caspase-3 (P<0.05). Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P<0.05) in SIPS. These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochromecrelease from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation. In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.

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Comparative Effects of Biodynes, Tocotrienol-Rich Fraction, and Tocopherol in Enhancing Collagen Synthesis and Inhibiting Collagen Degradation in Stress-Induced Premature Senescence Model of Human Diploid Fibroblasts

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/298574 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Suzana Makpol ◽

Faidruz Azura Jam ◽

Shy Cian Khor ◽

Zahariah Ismail ◽

Yasmin Anum Mohd Yusof ◽

...

Keyword(s):

Collagen Synthesis ◽

Skin Aging ◽

Collagen Degradation ◽

Type I ◽

Premature Senescence ◽

Diploid Fibroblasts ◽

Human Diploid Fibroblasts ◽

Protein Levels ◽

Stress Induced Premature Senescence ◽

Tocotrienol Rich Fraction

Biodynes, tocotrienol-rich fraction (TRF), and tocopherol have shown antiaging properties. However, the combined effects of these compounds on skin aging are yet to be investigated. This study aimed to elucidate the skin aging effects of biodynes, TRF, and tocopherol on stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs) by determining the expression of collagen and MMPs at gene and protein levels. Primary HDFs were treated with biodynes, TRF, and tocopherol prior to hydrogen peroxide (H2O2) exposure. The expression ofCOL1A1, COL3A1, MMP1, MMP2, MMP3,andMMP9genes was determined by qRT-PCR. Type I and type III procollagen proteins were measured by Western blotting while the activities of MMPs were quantified by fluorometric Sensolyte MMP Kit. Our results showed that biodynes, TRF, and tocopherol upregulated collagen genes and downregulatedMMPgenes (P<0.05). Type I procollagen and type III procollagen protein levels were significantly increased in response to biodynes, TRF, and tocopherol treatment (P<0.05) with reduction in MMP-1, MMP-2, MMP-3, and MMP-9 activities (P<0.05). These findings indicated that biodynes, TRF, and tocopherol effectively enhanced collagen synthesis and inhibited collagen degradation and therefore may protect the skin from aging.

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Cell cycle regulation in H2O2-induced premature senescence of human diploid fibroblasts and regulatory control exerted by the papilloma virusE6 and E7 proteins

Experimental Gerontology ◽

10.1016/s0531-5565(00)00167-4 ◽

2000 ◽

Vol 35 (6-7) ◽

pp. 733-745 ◽

Cited By ~ 30

Author(s):

C Frippiat ◽

Q.M Chen ◽

J Remacle ◽

O Toussaint

Keyword(s):

Cell Cycle ◽

Cell Cycle Regulation ◽

Regulatory Control ◽

Premature Senescence ◽

Diploid Fibroblasts ◽

Human Diploid Fibroblasts ◽

E7 Proteins ◽

Cycle Regulation

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Increased abundance of cytoplasmic and nuclear caveolin 1 in human diploid fibroblasts in H2O2-induced premature senescence and interplay with p38αMAPK

FEBS Letters ◽

10.1016/j.febslet.2008.04.026 ◽

2008 ◽

Vol 582 (12) ◽

pp. 1685-1692 ◽

Cited By ~ 27

Author(s):

Aline Chrétien ◽

Neil Piront ◽

Edouard Delaive ◽

Catherine Demazy ◽

Noëlle Ninane ◽

...

Keyword(s):

Premature Senescence ◽

Caveolin 1 ◽

Diploid Fibroblasts ◽

Human Diploid Fibroblasts

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DRG2 Accelerates Senescence via Negative Regulation of SIRT1 in Human Diploid Fibroblasts

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/7301373 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Bing Si Li ◽

Ai Lin Jin ◽

ZiQi Zhou ◽

Jae Ho Seo ◽

Byung-Min Choi

Keyword(s):

Oxidative Stress ◽

Cell Growth ◽

Binding Protein ◽

Ectopic Expression ◽

Sirtuin 1 ◽

Premature Senescence ◽

Gtp Binding Protein ◽

Human Diploid Fibroblasts ◽

Gtp Binding ◽

Stress Induced Premature Senescence

Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study, we found that endogenous DRG2 protein expression is upregulated in oxidative stress-induced premature senescence models and tissues of aged mice. Ectopic expression of DRG2 significantly promoted senescence-associated β-galactosidase (SA-β-gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-κB) p65 (Lys310), p21Waf1/Cip1, and p16Ink4a and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming γ-H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-κB p65. Additionally, DRG2 knockdown significantly abolished oxidative stress-induced premature senescence. Our results provide a possible molecular mechanism for investigation of cellular senescence and aging regulated by DRG2.

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