Changes And Development Of The Aging Process

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Epigenetic changes are currently recognized as part of the aging process and have been implicated in many age-related chronic diseases such as AD (1–3). The term epigenetics includes a variety of processes known to regulate gene expression in a stable and potentially reversible way, without altering the primary DNA sequence (4). Since epigenetics allow for the integration of long-lasting non-genetic inputs in the genome, research on age-related disorders have recently focused in epigenetic mechanisms, and a growing number of epigenetic alterations in AD have been described recently (5). The best characterized epigenetic mechanisms include DNA methylation, histone posttranslational modifications, and non-coding RNAs such as microRNAs (miRNAs). It is becoming increasingly evident the interplay between these mechanisms to establish the epigenetic states and expression patterns of many mammalian genes (1–3). For instance, it has been described that trimethylation of histone 3 at lysine 9 (H3K9me3) by the histone methyl transferase SUV39H1 is required for recruiting the DNA methyl transferase DNMT3b to pericentromeric repeats in order to allow heterochromatin structure (both H3-K9 methylation and DNA methylation are considered hallmarks of mammalian heterochromatin) (4). In turn, miRNAs can also control other epigenetic mechanisms; for example, miR-204 can target histone deacetylase 4 (HDAC4) (5), while miR-148 and miR-152 are reported to influence DNA methylation
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