An epigenetic accelerated ageing syndrome links DNA methylation to multi-tissue pathology

An epigenetic accelerated ageing syndrome links DNA methylation to multi-tissue pathology

Prof Andrew Jackson; University of Edinburgh

Professor Andrew Jackson is a Programme Leader at the MRC Human Genetics Unit, University of Edinburgh, and also practices as a Consultant in Clinical Genetics. He studied medicine at Newcastle University (1993) and completed his PhD at Leeds University (2001), before moving to Edinburgh to start his own group in 2007. Andrew was elected as a Fellow of the Royal Society (2020), the Royal Society of Edinburgh (2014) and the Academy of Medical Sciences (2014), and is a member of EMBO (2013). The Jackson lab identifies genes for Mendelian disorders affecting human brain size and defines the functional role of the encoded proteins using multidisciplinary and multiscale approaches. The ultimate aim is to harness human phenotypes to gain new insights into basic biological processes and extend understanding of human disease mechanisms for common diseases, cancer and ageing.

Our lab has a long-standing interest in extreme growth disorders, ‘the smallest people in the world’. In these monogenic diseases, mutations result in changes to the total cell number, leading to hypocellular dwarfism. While growth disorders occur at the opposite end of life to ageing, recently we have unexpectedly found age-related pathologies in one of these conditions. Here, I will outline this novel accelerated ageing syndrome, which recapitulates age-related gains in DNA methylation. This disorder could inform our understanding of the ‘Epigenetics alterations’ hallmark of ageing, as it causally implicates DNA methylation in the aetiology of various medically important haematological, bone and metabolic pathologies. Furthermore, our findings suggest a role for stem-cell dysfunction in both somatic growth and ageing.

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