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Aging is a multi-factorial process of the progressive gradual decline of cellular functions with the passage of time. It is clear that aging affects the mammalian epigenome, including hypomethylation of DNA. DNA methylation is a crucial biological process that controls maintenance of genomic integrity and an accurate expression of genetic information. The accurate status of DNA methylation is balanced...
Aging is linked to a number of changes in gene expression that are associated with ‘normal’ or ‘pathologic’ aging (reviewed in Weindruch and Prolla, 2002; Toescu et al., 2004; Park and Prolla, 2005; Englander, 2005). As such, a number of studies have focused on the mechanism(s) underlying these changes in an attempt to identify conserved pathways altered during aging. Methylation of DNA is a critical...
Histones, once thought of as static structural elements, are now known to be dynamic and integral elements of the machinery responsible for regulating gene transcription. Modification of histones and/or DNA can alter the strength of their association and thus, together, modulate transcriptional activity. Acetylation of histones neutralizes their positively charged, lysine-rich amino-terminal tails,...
Sirtuins are a family of highly conserved genes widely distributed in organisms ranging from bacteria to humans. Mounting evidence has revealed the important role of sirtuins in a variety of biological processes, including transcription regulation, apoptosis, DNA repair, metabolism, and more prominently, aging. Sirtuins regulate lifespan in evolutionarily diverse species partly through modulating...
Cellular senescence is thought to contribute to tissue aging. The role of Wnt signaling in aging is little studied and poorly understood, but there is evidence that Wnt signaling can be both pro- and anti-aging. Here we discuss the idea that, in at least some cell and tissue contexts, Wnt signaling might antagonize aging through its ability to regulate chromatin structure in senescent cells.
S-adenosylmethionine (SAM) is a sulfur-containing molecule at the heart of metabolism of all organisms. It is well known as the methyl donor for the majority of methyltransferases that modify DNA, RNA, histones, and many other proteins such as Tp53, lipids, and a variety of other small molecules including toxic compounds, such as arsenic, whose actions affect replication, transcription,...
Although there has been considerable interest in the aging process for quite some time and in epigenetics for over two decades, it is relatively recent that we have witnessed a surge in interest in aging epigenetics. Epigenetic processes are vast and influence many genes and other processes related to aging that impact the physiological decline that characterizes the aging process. This ranges from...
Individuals of all ages can be detrimentally affected by cancer, albeit the disease is more prevalent in aging individuals. Epigenetic modulation is essential for normal development and becomes altered in cancer and aging. The most well-studied epigenetic elements include DNA methylation, histone modifications, miRNAs, and the binding of co-regulatory proteins such as Polycomb group and Trithorax...
Epigenetics plays a direct and indirect role in the chances of developing Alzheimer’s disease. The decreased DNA methylation status with increasing age of the amyloid precursor protein (APP) gene promoter will boost transcription of this gene, leading to higher levels of APP. Furthermore, both the BACE and PS1 genes show similar decreased promoter methylation with aging, causing higher levels – and...
The adaptive immune system is a highly proliferative organ that combines ongoing differentiation with preservation of memory. CpG DNA methylation is central to many of the fate decisions that occur from early lymphoid development to late effector functions of end-differentiated cells. Many of the DNA demethylation-sensitive genes play an important role in autoimmune diseases and in the immune defects...
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