Genetic and Epigenetic Regulation of Telomere Length: Current Findings, Methodological Limitations and Possibilities for Future Studies

Abstract

Telomeres are TTAGGG repeats located at the end of chromosomes that maintain DNA stability. Telomere length (TL) has been widely implicated as a marker of biological age, and is associated with several human diseases, including depression, cardiovascular disease and cancer. Twin studies and cohort studies estimate heritability of TL between 78-82%. Moreover, several genomic loci which influence TL have been identified. Despite the success of genetic studies in furthering our understanding of telomere biology, identified variants account for only a small proportion of the estimated heritability. Over the last decade, epigenetic regulation of mammalian telomeres has become apparent. These epigenetic mechanisms, which act to regulate gene expression via modifications to DNA, histone proteins and chromatin, change with age and in response to specific environmental and psychosocial factors —providing a mechanism for the interaction between genotype and the environment. The present review examines the evidence for genetic and epigenetic regulation of TL and discusses their role in human disease, before outlining some of the methodological limitations of these studies. Finally, the review defines what the ‘epigenetic clock’ is and evaluates its relationship with TL.