scholarly journals Expression of Senescence-Associated microRNAs and Target Genes in Cellular Aging and Modulation by Tocotrienol-Rich Fraction

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Sharon Gwee Sian Khee ◽  
Yasmin Anum Mohd Yusof ◽  
Suzana Makpol
Keyword(s):  
Cellular Senescence ◽  
Target Genes ◽  
Replicative Senescence ◽  
Primary Cultures ◽  
Ectopic Expression ◽  
Cellular Aging ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts ◽  
Tocotrienol Rich Fraction

Emerging evidences highlight the implication of microRNAs as a posttranscriptional regulator in aging. Several senescence-associated microRNAs (SA-miRNAs) are found to be differentially expressed during cellular senescence. However, the role of dietary compounds on SA-miRNAs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on SA-miRNAs (miR-20a, miR-24, miR-34a, miR-106a, and miR-449a) and established target genes of miR-34a (CCND1, CDK4, and SIRT1) during replicative senescence of human diploid fibroblasts (HDFs). Primary cultures of HDFs at young and senescent were incubated with TRF at 0.5 mg/mL. Taqman microRNA assay showed significant upregulation of miR-24 and miR-34a and downregulation of miR-20a and miR-449a in senescent HDFs (P<0.05). TRF reduced miR-34a expression in senescent HDFs and increased miR-20a expression in young HDFs and increased miR-449a expression in both young and senescent HDFs. Our results also demonstrated that ectopic expression of miR-34a reduced the expression of CDK4 significantly (P<0.05). TRF inhibited miR-34a expression thus relieved its inhibition on CDK4 gene expression. No significant change was observed on the expression of CCND1, SIRT1, and miR-34a upstream transcriptional regulator, TP53. In conclusion tocotrienol-rich fraction prevented cellular senescence of human diploid fibroblasts via modulation of SA-miRNAs and target genes expression.

scholarly journals Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

Aging Cell ◽  
2015 ◽  
Vol 15 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Kyeong Eun Yang ◽  
Hyun‐Jin Jang ◽  
In‐Hu Hwang ◽  
Young‐Ho Chung ◽  
Jong‐Soon Choi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cellular Senescence ◽  
Nitric Oxide Production ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts ◽  
Oxide Production

scholarly journals SIRT1 Overexpression Antagonizes Cellular Senescence with Activated ERK/S6k1 Signaling in Human Diploid Fibroblasts

PLoS ONE ◽  
2008 ◽  
Vol 3 (3) ◽  
pp. e1710 ◽  
Author(s):  
Jing Huang ◽  
Qini Gan ◽  
Limin Han ◽  
Jian Li ◽  
Hai Zhang ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts

scholarly journals Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts.

1989 ◽  
Vol 9 (7) ◽  
pp. 3088-3092 ◽  
Author(s):  
W E Wright ◽  
O M Pereira-Smith ◽  
J W Shay
Keyword(s):  
Cellular Senescence ◽  
Rare Event ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts ◽  
Normal Human ◽  
Immortal Cells ◽  
Cellular Dna

IMR-90 normal human diploid fibroblasts, transfected with a steroid inducible mouse mammary tumor virus-driven simian virus 40 T antigen, were carried through crisis to yield an immortal cell line. Growth was dependent on the presence of the inducer (dexamethasone) during both the extended precrisis life span of the cells and after immortalization. After dexamethasone removal, immortal cells divided once or twice and then accumulated in G1. These results are best explained by a two-stage model for cellular senescence. Mortality stage 1 (M1) causes a loss of mitogen responsiveness and arrest near the G1/S interface and can be bypassed or overcome by the cellular DNA synthesis-stimulating activity of T antigen. Mortality stage 2 (M2) is an independent mechanism that is responsible for the failure of cell division during crisis. The inactivation of M2 is a rare event, probably of mutational origin in human cells, independent of or only indirectly related to the expression of T antigen. Under this hypothesis, T-antigen-immortalized cells contain an active but bypassed M1 mechanism and an inactivated M2 mechanism. These cells are dependent on the continued expression of T antigen for the maintenance of immortality for the same reason that precrisis cells are dependent on T antigen for growth: both contain an active M1 mechanism.

scholarly journals Nucleolar stress causes the entry into replicative senescence in budding yeast

2018 ◽  
Author(s):  
Sandrine Morlot ◽  
Song Jia ◽  
Isabelle Léger-Silvestre ◽  
Audrey Matifas ◽  
Olivier Gadal ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Molecular Mechanisms ◽  
Replicative Senescence ◽  
Cellular Aging ◽  
Daughter Cells ◽  
Nucleolar Stress ◽  
Unique Framework ◽  
Massive Accumulation

SummaryThe accumulation of Extrachromosomal rDNA Circles (ERCs) and their asymmetric segregation upon division have been hypothesized to be responsible for replicative senescence in mother yeasts and rejuvenation in daughter cells. However, it remains unclear by which molecular mechanisms ERCs would trigger the irreversible cell cycle slow-down leading to cell death. We show that ERCs accumulation is concomitant with a nucleolar stress, characterized by a massive accumulation of pre-rRNAs in the nucleolus, leading to a loss of nucleus-to-cytoplasm ratio, decreased growth rate and cell-cycle slow-down. This nucleolar stress, observed in old mothers, is not inherited by rejuvenated daughters. Unlike WT, in the long-lived mutant fob1∆, a majority of cells is devoid of nucleolar stress and does not experience replicative senescence before death. Our study provides a unique framework to order the successive steps that govern the transition to replicative senescence and highlights the causal role of nucleolar stress in cellular aging.

scholarly journals Aminoguanidine delays the replicative senescence of human diploid fibroblasts

2007 ◽  
Vol 120 (22) ◽  
pp. 2028-2035 ◽  
Author(s):  
Pei-chang WANG ◽  
Jian ZHANG ◽  
Zong-yu ZHANG ◽  
Tan-jun TONG
Keyword(s):  
Replicative Senescence ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts

scholarly journals Stereoisomer-specific ginsenoside 20(S)-Rg3 reverses replicative senescence of human diploid fibroblasts via Akt-mTOR-Sirtuin signaling

2020 ◽  
Vol 44 (2) ◽  
pp. 341-349 ◽  
Author(s):  
Kyeong-Eun Yang ◽  
Hyun-Jin Jang ◽  
In-Hu Hwang ◽  
Eun Mi Hong ◽  
Min-Goo Lee ◽  
...  
Keyword(s):  
Replicative Senescence ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts
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