Aging as an Epigenetic Phenomenon

Abstract

Introduction:Hypermethylation of genes associated with promoter CpG islands, and hypomethylation of CpG poor genes, repeat sequences, transposable elements and intergenic genome sections occur during aging in mammals. Methylation levels of certain CpG sites display strict correlation to age and could be used as “epigenetic clock” to predict biological age. Multi-substrate deacetylases SIRT1 and SIRT6 affect aging via locus-specific modulations of chromatin structure and activity of multiple regulatory proteins involved in aging. Random errors in DNA methylation and other epigenetic marks during aging increase the transcriptional noise, and thus lead to enhanced phenotypic variation between cells of the same tissue. Such variation could cause progressive organ dysfunction observed in aged individuals. Multiple experimental data show that induction of NF-κB regulated gene sets occurs in various tissues of aged mammals. Upregulation of multiple miRNAs occurs at mid age leading to downregulation of enzymes and regulatory proteins involved in basic cellular functions, such as DNA repair, oxidative phosphorylation, intermediate metabolism, and others.Conclusion:Strong evidence shows that all epigenetic systems contribute to the lifespan control in various organisms. Similar to other cell systems, epigenome is prone to gradual degradation due to the genome damage, stressful agents, and other aging factors. But unlike mutations and other kinds of the genome damage, age-related epigenetic changes could be fully or partially reversed to a “young” state.

A non-Lamarckian model for the inheritance of the epigenetically-coded phenotypic characteristics: a new paradigm for Genetics, Genomics and, above all, Ageing studies

“…On the other hand, although the association of ageing and epigenetics is not new, in recent years there has been an increasing amount of evidences that imply epigenetics as the main actor in ageing (Horvath, 2013;Zhang et al, 2015;Ocampo et al, 2016;Sen et al, 2016;Ashapkin et al, 2017;Maierhofer et al, 2017;Marsellach, 2017), even proposing epigenetics as the only cause of ageing (Gibbs, 2014;Ocampo et al, 2016;Marsellach, 2017). Nevertheless, to date there has not been any coherent explanation on how variability in the epigenome can drive ageing.…”

Sleep Apnoea and Early Antecedents of Adult Disease

“…Numerous studies have subsequently documented associations between low birth weight and increased incidence of heart disease, hypertension, and type 2 diabetes, as well as relevant markers such as insulin resistance and dyslipidaemias 18,19 . Extrapolation of this early exposure linkage to other diseases such as cancer, neurodegenerative disorders and overall accelerated ageing has gained substantial traction in recent years, further attesting to the importance of internal and external environmental cues to the modulation of homeostatic processes, including those involved in tissue repair and regeneration [20][21][22][23][24][25] .…”

Molecular Basis of Neurodegeneration: Lessons from Alzheimer’s and Parkinson’s Diseases

“…In this regard, ageing constitutes a natural, highly complex process that involves the progressive decay of several biological systems. Moreover, genetic and epigenetic heterogeneity introduces variation in the ageing process from one individual to another [2,3]. In addition, an increased lifespan implies longer exposure to environmental pollutants that able to interact and modify different biological molecules, including DNA, not only affecting the functionality but also favouring the insurgence of several chronic degenerative disorders (http:// www.iarc.fr).…”