Biological ageing is a key determinant in systemic sclerosis

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune cell activation and fibrosis of the skin and internal organs, occurring mainly in females. Although a lot of progress has been made in the discovery of genetic risk factors for SSc, environmental factors triggering onset of SSc have not been identified. This provides a foundation for the involvement of processes related to biological ageing to trigger SSc onset and perpetuation in the genetically susceptible host. Consequently, we have investigated key determinants of biological ageing, namely telomere attrition and the role of telosome proteins in the pathology of systemic sclerosis and how it impacts on individual leukocyte cell subsets. Epigenetic processes, such as telomere attrition have been implicated in SSc [1]. The length of telomeric DNA repeats shortens during replicative ageing of peripheral blood lymphocytes. This process is exacerbated by psychological, sociological and biological determinants [2,3]. As a consequence, telomere length reflects the “miles on the clock” of a given cell type. Proteinaceous components of the associatedtelosome arecomplicit in the sensing, signaling and repair of DNA damage [3]. These have a critical role inprotectingthe cell from excessive DNA damage, by facilitating cellular senescence and apoptosis. This study aimed to evaluate telosome biologyin an independent, clinically well-defined SSc cohorts. Moreover, we aimed to investigate whether there are differences in telomere attrition between different immune cell subsets and if these differences are accompanied by changes in expression of genes involved in telomere functioning.