Aging is an unstoppable process coupled to the loss of physiological function and increased susceptibility to diseases. Epigenetic alteration is one of the hallmarks of aging, which involves changes in DNA methylation patterns, post-translational modification of histones, chromatin remodeling and non-coding RNA interference. Invertebrate model organisms, such as Drosophila melanogaster and Caenorhabditis elegans, have been used to investigate the biological mechanisms of aging because they show, evolutionarily, the conservation of many aspects of aging. In this review, we focus on recent advances in the epigenetic changes of aging with invertebrate models, providing insight into the relationship between epigenetic dynamics and aging. conserved in both insects and mammals, where it regulates the rate of aging [11]. Therefore, this review will summarize recent advances in the roles of epigenetic changes in aging in these two invertebrates.
DNA Methylation in Invertebrate AgingDNA methylation is a covalent chemical modification, which usually occurs at 5-methyl cytosine (5mC) and which is enriched in cytosine phosphate guanine (CpG) dinucleotides [12]. CpG methylation within promoters leads to transcriptional repression through the formation of compact chromatin structures such as heterochromatin. Conversely, promoters of genes that are highly expressed are devoid of DNA methylation, hence their name-CpG islands [13]. The dynamic changes in DNA methylation can impact aging and health. The local methylation level increases while the global methylation level decreases with aging [14]. Age-related DNA methylation changes are also correlated with human age-related diseases, such as cancer and sarcopenia [15,16]. Cytosine methylation is catalyzed by three DNA methyltransferases (DNMTs): DNMT1, DNMT3a, and DNMT3b. Three ten-eleven translocation (TET) proteins initiate the specific demethylation of 5mC residues in DNA: TET1, TET2, and TET3 [17]. The schematic diagram of DNA methylation and demethylation is shown in Figure 1. Worms do not encode a conventional DNA methyltransferase to silence DNA repeats, which led to the prevailing view that DNA methylation does not occur in C. elegans [18]. Similarly, in adult D. melanogaster, only a low level of DNA methylation was confirmed [19,20]. In Drosophila, overexpression of the DNA methyltransferase gene, dDnmt2, extends lifespan in a small heat shock protein-dependent way [21]. However, although 5mC methylation is rare, methylation on N6 adenine (6mA) is prevalent in C. elegans and D. melanogaster [22,23]. Recent studies have confirmed that NMAD-1 (MT-A70 family) and DMAD (DNA 6mA demethylase, TET ortholog) are 6mA demethylases in C. elegans and D. melanogaster, respectively. DAMT-1 (AlKB family) is likely a 6mA methyltransferase in C. elegans [24]. NMAD-1 and DAMT-1 can regulate 6mA levels and control the epigenetic inheritance of phenotypes associated with the loss of the H3K4me2 demethylase spr-5 [22]. The worm mutant of spr-5 displayed a transgenerational increase in H3K4me...