The methylation of nuclear and mitochondrial DNA in ageing phenotypes and longevity

• Published in: Mechanisms of ageing and development 2017-07, Vol.165 (Pt B), p.156-161
• Main Authors: Bacalini, Maria Giulia, D’Aquila, Patrizia, Marasco, Elena, Nardini, Christine, Montesanto, Alberto, Franceschi, Claudio, Passarino, Giuseppe, Garagnani, Paolo, Bellizzi, Dina
• Format: Article
• Language: English
• Subjects: Ageing; Ageing phenotypes; Animals; Centenarians; CpG Islands - physiology; DNA Methylation - physiology; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Epigenesis, Genetic - physiology; Epigenetic clock; Epigenetic drift; Humans; Longevity; Longevity - physiology; Mitochondrial DNA methylation; Nuclear DNA methylation
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2017.01.006

•Epigenetic events contribute to the complexity of ageing process.•A global decline of genomic DNA methylation as well as gene-specific hyper- and hypomethylation occur during ageing.•Stochastic or environmental factors contribute to the DNA methylation variability at certain CpG sites (epigenetic drift).•Mitochondrial DNA methylation changes involving both regulatory and coding regions are emerging to play a role in ageing. An increasing body of data is progressively indicating that the comprehension of the epigenetic landscape, actively integrated with the genetic elements, is crucial to delineate the molecular basis of the inter-individual complexity of ageing process. Indeed, it has emerged that DNA methylation changes occur during ageing, consisting mainly in a progressive process of genome demethylation, in a hypermethylation of gene-specific CpG dinucleotides, as well as in an inter-individual divergence of the epigenome due to stochastic events and environmental exposures throughout life, namely as epigenetic drift. Additionally, it has also come to light an implication of the mitochondrial genome in the regulation of the intracellular epigenetic landscape, as demonstrated by the being itself object of epigenetic modifications. An overview of DNA methylation changes occurring during ageing process at both nuclear and mitochondrial level will be described in this review, also taking into account the recent and promising data available on the 5-hydroxymethylcytosine.