Epigenetic modulation by melatonin: clinical implications and therapeutic prospects

Abstract

The existence of nonadditive primary interactions between genes and the environment is a nearly axiomatic concept in current biomedicine for the origin of diseases. Thus, the classic interaction between inheritance and environmental factors becomes crucial for understanding the etiology of common multifactorial disorders, which strongly depend on nongenetic factors, as well as the phenotypic discrepancies observed in cases of closer genotype-phenotype relationships between individuals with identical genetic profiles. The fundamental premise is that inherited variants predispose individuals to complex phenotypic traits, such as susceptibility to cancer or the risk of developing Alzheimer’s disease. However, cross-associative interactions with the physical environment and lifestyle ultimately determine the onset and severity of the disease. The interface for cross-communication between genotype and phenotype consists of a collection of chemical switches imprinted on the genome, capable of reversibly activating or deactivating genes in response to environmental (or endogenous) conditions. Known as the epigenome, recent research has revealed the decisive role that epigenetic marks play in cell/tissue differentiation and in the plasticity of gene expression patterns.