DNA Methylation

Publication Title: 
Oncogene

Human keratinocytes grown in co-culture with fibroblast feeder cells have an extended in vitro lifespan and delayed accumulation of the tumor suppressor protein p16(INK4a) when compared to the same cells grown on tissue culture plastic alone. Previous studies have indicated that human keratinocytes can be immortalized by telomerase activity alone when grown in co-culture with feeder cells, suggesting that loss of the p16(INK4a)/Rb pathway is not required for immortalization.

Author(s): 
Darbro, B. W.
Lee, K. M.
Nguyen, N. K.
Domann, F. E.
Klingelhutz, A. J.
Publication Title: 
Age (Dordrecht, Netherlands)

Dietary restriction (DR) increases lifespan in a range of evolutionarily distinct species. The polyphenol resveratrol may be a dietary mimetic of some effects of DR. The pivotal role of the mammalian histone deacetylase (HDAC) Sirt1, and its homologue in other organisms, in mediating the effects of both DR and resveratrol on lifespan/ageing suggests it may be the common conduit through which these dietary interventions influence ageing.

Author(s): 
Wakeling, Luisa A.
Ions, Laura J.
Ford, Dianne
Publication Title: 
FASEB journal: official publication of the Federation of American Societies for Experimental Biology

Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells.

Author(s): 
Li, Yuanyuan
Liu, Liang
Tollefsbol, Trygve O.
Publication Title: 
Experimental Gerontology

DNA methylation patterns change as individuals grow older, and DNA methylation appears susceptible to modification by the diet. Thus DNA methylation may be a mechanism through which diet can affect aging and longevity. We propose that effects on DNA methylation also contribute to the extension in lifespan observed in response to dietary restriction. Relationships between diet-induced changes in DNA methylation and parallel effects on aging and/or lifespan could, of course, be purely associative.

Author(s): 
Ford, Dianne
Publication Title: 
Molecular Biology of the Cell

Forkhead box O (FOXO) transcription factors control diverse cellular functions, such as cell death, metabolism, and longevity. We analyzed FOXO3/FKHRL1 expression and subcellular localization in tumor sections of neuroblastoma patients and observed a correlation between nuclear FOXO3 and high caspase-8 expression. In neuroblastoma caspase-8 is frequently silenced by DNA methylation. Conditional FOXO3 activated caspase-8 gene expression but did not change the DNA-methylation pattern of regulatory sequences in the caspase-8 gene.

Author(s): 
Geiger, Kathrin
Hagenbuchner, Judith
Rupp, Martina
Fiegl, Heidi
Sergi, Consolato
Meister, Bernhard
Kiechl-Kohlendorfer, Ursula
M¸ller, Thomas
Ausserlechner, Michael J.
Obexer, Petra
Publication Title: 
PLoS genetics

Age-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes.

Author(s): 
Bell, Jordana T.
Tsai, Pei-Chien
Yang, Tsun-Po
Pidsley, Ruth
Nisbet, James
Glass, Daniel
Mangino, Massimo
Zhai, Guangju
Zhang, Feng
Valdes, Ana
Shin, So-Youn
Dempster, Emma L.
Murray, Robin M.
Grundberg, Elin
Hedman, Asa K.
Nica, Alexandra
Small, Kerrin S.
MuTHER Consortium
Dermitzakis, Emmanouil T.
McCarthy, Mark I.
Mill, Jonathan
Spector, Tim D.
Deloukas, Panos
Publication Title: 
Experimental Gerontology

DNA methylation patterns change as individuals grow older, and DNA methylation appears susceptible to modification by the diet. Thus DNA methylation may be a mechanism through which diet can affect aging and longevity. We propose that effects on DNA methylation also contribute to the extension in lifespan observed in response to dietary restriction. Relationships between diet-induced changes in DNA methylation and parallel effects on aging and/or lifespan could, of course, be purely associative.

Author(s): 
Ford, Dianne
Publication Title: 
Molecular Aspects of Medicine

While the eukaryotic genome is the same throughout all somatic cells in an organism, there are specific structures and functions that discern one type of cell from another. These differences are due to the cell's unique gene expression patterns that are determined during cellular differentiation. Interestingly, these cell-specific gene expression patterns can be affected by an organism's environment throughout its lifetime leading to phenotypical changes that have the potential of altering risk of some diseases.

Author(s): 
Tammen, Stephanie A.
Friso, Simonetta
Choi, Sang-Woon
Publication Title: 
Rejuvenation Research

Methylation of DNA is intimately involved in control of mammalian/vertebrate gene expression as part of a complex epigenetic regulatory system. We hypothesize that DNA methylation at cytosine-phosphate-guanine sites (CpGs), the "DNA methylome," evolved to increase stability of the differentiated state in somatic vertebrate cells, especially post-mitotic cells, which may have helped to increase longevity. Therefore, the DNA methylome may play a key role in human aging and be an ideal source of biomarkers aging.

Author(s): 
Mendelsohn, Andrew R.
Larrick, James W.
Publication Title: 
Experimental Cell Research

Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood.

Author(s): 
Becerikli, Mustafa
Jacobsen, Frank
Rittig, Andrea
Kˆhne, Wiebke
Nambiar, Sandeep
Mirmohammadsadegh, Alireza
Stricker, Ingo
Tannapfel, Andrea
Wieczorek, Stefan
Epplen, Joerg Thomas
Tilkorn, Daniel
Steinstraesser, Lars

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