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In muscles of aged flies, TFAM and mtDNA have been found to form a more condensed structure than in juveniles ( Recently, it has been observed that DNA methyltransferase 3 alpha (DNMT3A) and ten-even-transposon 2 (TET2) regulates the TFAM expression in macrophages ( IFN ) production with subsequent increase in inflammation ( Notably, in aging is well known the increasing of inflammation state (named inflammaging) which involved several cytokines included IFN ( It is well known that nuclear translocation of p53 protein is associated with increased aging due to its inhibition of PPAR co-activator 1 (PGC1) and PGC1 ( Methylation of mtDNA Another epigenetic modification that occurs in aging is the global decrease in the level of methylation in genomic DNA, which cooperates with the modification of histones ( Although the most representative methylated base in mtDNA is adenine, recent work shows a correlation between aging and 5 mC methylation of mtDNA in the brain, where some 5 mCs (in this case both CpG and non-CpG) were found to be modulated (69, 69)