The research highlighted throughout this chapter has only briefly summarized an exceptional amount of work that has contributed to our understanding of the roles DNA methylation plays in health and ageing. It is becoming increasingly evident that DNA methylation functions as the interface of genetic sequence, environmental exposures, and phenotypic outcomes. Thus, it is tempting to speculate that this critical epigenetic mark can be extremely useful to our understanding of health, either through functional contributions or as biomarkers of human phenotypes and diseases.
Although there is an indisputable association between DNA methylation and chronological age throughout the entirety of life, even to the point of developing extremely accurate DNA methylation-based age predictors, it is still not clear what functional role DNA methylation plays in the ageing process. One possible scenario is that epigenetic drift may represent embedding of unique environmental exposures across the lifetime, resulting in increased divergence of DNA methylation profiles with age. Under this model, sites that correlate linearly with chronological age, such as those used for epigenetic clocks, may represent markers of biological ageing and give a molecular insight into the ageing process. On the other hand, it is also possible that age-associated DNA methylation changes do not have a functional component. Under this assumption, epigenetic drift may not reflect environments, but random changes with time, and the epigenetic clock may simply represent those regions of the genome which are more susceptible to age-related changes across individuals . However, the finding that epigenetic age acceleration is correlated with mortality and disease suggests a specific role for common epigenetic changes with age, and further research is needed to clarify its functional relevance.
Despite our gaps in understanding the mechanistic function of DNA methylation in immunity and ageing, it is apparent that methylation is associated with events and exposures that shape an individual’s lifelong health. The further we explore these associations, the more it becomes clear that DNA methylation has a significant position in the complex process of ageing and age-related diseases.