Abstract
Functional studies of organisms and human models have revealed that epigenetic changes can significantly impact the process of aging. Non-coding RNA (ncRNA), one of epigenetic regulators, plays an important role in modifying the expression of mRNAs and their proteins. It can mediate the phenotype of cells. It has been reported that nc886 (=vtRNA2-1 or pre-miR-886), a long ncRNA, can suppress tumor formation and photo-damages of keratinocytes caused by UVB. The aim of this study was to determine the role of nc886 in replicative senescence of fibroblasts and determine whether substances capable of controlling nc886 expression could regulate cellular senescence. In replicative senescence fibroblasts, nc886 expression was decreased while methylated nc886 was increased. There were changes of senescence biomarkers including SA-β-gal activity and expression of p16INK4A and p21Waf1/Cip1 in senescent cells. These findings indicate that the decrease of nc886 associated with aging is related to cellular senescence of fibroblasts and that increasing nc886 expression has potential to suppress cellular senescence. AbsoluTea Concentrate 2.0 (ATC) increased nc886 expression and ameliorated cellular senescence of fibroblasts by inhibiting age-related biomarkers. These results indicate that nc886 has potential as a new target for anti-aging and that ATC can be a potent epigenetic anti-aging ingredient.
Highlights
Cellular senescence in an irreversible state following cell proliferation arrest has emerged as a potentially important contributor to tissue dysfunction and aging of organisms [1]
We have found that the reduction of nc886 expression caused by UVB irradiation is associated with increases of COX-2 and matrix metalloproteinases (MMPs)-9 through protein kinase RNA-activated (PKR) pathway in keratinocytes and that promotion of nc886 expression can be a useful strategy to develop UVB protective materials [9,10]
We investigated the role of nc886 in replicative senescence of fibroblasts and determined whether highly concentrated green tea 3”Me-epigallocatechin gallate (EGCG) preparation (AbsoluTea Concentrate 2.0) that could increase nc886 expression could improve cellular senescence
Summary
Cellular senescence in an irreversible state following cell proliferation arrest has emerged as a potentially important contributor to tissue dysfunction and aging of organisms [1]. Senescence is characterized by high activity of senescence-associated betagalactosidase (SA-β-gal), increase expression of senescence biomarkers such as p16INK4A and p21Waf1/Cip, and decreased expression of LaminB1 [2]. There are two basic types of cellular senescence: replicative senescence and stress-induced premature senescence. Replicative senescence is defined as the phenomenon when normal cells stop dividing after reaching limited numbers of divisions. Continuous damage accumulation can induce replicative senescence of fibroblasts, leading to lost ability to remodel and organize the extracellular matrix (ECM). Main features of aged dermis are reduced amount of collagen fibers and increased production of matrix metalloproteinases (MMPs), which contribute to a thin and disorganized structure of dermis [3,4]
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