Switch theory in practice: a model to decipher the complexity of longevity

The aging process is generally associated with the development of various chronic diseases such as CVD, T2D and AD. Advances in medical care have promoted lifespan beyond reproduction age mostly by curing childhood diseases; as a result, in many cases medicine does not provide enough insights and protection against the new exposed age associated diseases (AAD). Genomics studies such as GWAS and WGS have provided some clues to the role of DNA in the aging and AAD processes, yet, they lack information regarding the functional aspect, as a result of epigenetic changes. Epigenetics can be classified as non-sequence-altering DNA modifications that can affect gene expression. The discovery of the methylation of DNA loci as a control and risk factor in AAD and mortality is a novel and significant concept expected to immensely enhance our understanding of the biological processes involved in aging.

Epigenetic mechanisms such as DNA methylation cites (CpG) are scattered throughout the genome and may serve as a “switch” to silence or evoke a target gene. However, unlike a simple switch, all components must work in harmony and the outcome depends on many factors. Excessive epigenetic sites offer the flexible and inherited DNA-sequence-independent adaptation to environmental changes by turning on or off the target gene due to gene-environment interactions. Thus aging, which can be characterized as a slow adaptation to physiological and environmental changes, would benefit greatly from excessive CpGs which add complexity to gene regulation and may provide a strong tool for adaptation that may promote longevity.