Christof Niehrs

Organismic ageing is accompanied by changes in DNA cytosine methylation levels. These changes are so stereotypic that “epigenetic clocks’ have been developed, most famously ‘Horvath’s clock’, using CpGs whose methylation level tightly correlates with biological age. These epigenetic clocks predict biological age and inform about the positive or negative deviation of biological from chronological age, as well as predicting time to death.

Although changes in epigenetic DNA methylation are the most accurate predictor of biological age and lifespan in man, it is still uncertain whether methylation changes affect ageing. Our research indicated that transcription factor access to cognate binding sites is regulated by DNA demethylation via TET methylcytosine dioxygenases and the epigenetic regulator Gadd45a. Deficiency in Gadd45a and Ing1b induces DNA methylation changes and leads to premature ageing in mice. Moreover, Gadd45a recognises certain DNA:RNA hybrids (R-loops) and long noncoding RNAs (lncRNAs) in stem cells. We therefore investigate the connections between DNA demethylation, regulatory R-loops, lncRNAs and ageing.

In an interdisciplinary project, we also investigate the utility of Horvath’s clock in studying heart failure (HF), a common age-associated disease with growing prevalence due to increasing life expectancy and demographic change. HF represents a high medical and economic burden and is the most frequent cause of hospitalisation. To stratify HF and predict patient outcomes, we employ Horvath’s clock as a molecular parameter.

Research website