The link: DNA repair and aging

Evidence that DNA damage has a huge impact on the ageing process comes from different human inherited disorders, in which genes are affected that are involved in genome maintenance, like Trichothiodystrophy (TTD), Cockayne Syndrome (CS) and Werner Syndrome (WS), the first two being affected in genes that are involved in NER. Patients suffering from these diseases show many features of segmental premature ageing such as neurodegeneration, osteoporosis, sarcopenia, growth deficiency, fat redistribution, graying and loss of hair, wrinkled skin, and shortened life span.

To further test the hypothesis that DNA damage accumulation leads to ageing, Hoeijmakers et al. developed a large series of mouse models in which the genes for several DNA repair proteins were mutated. One of the mouse models generated mimics a mutation that was found in patients suffering from Trichothiodystrophy (TTD). This mouse phenotypically resembles the patient to a striking degree, including the characteristic features of brittle hair, scaly skin as well as early cessation of development and reduced life span. Mouse models were also developed on the basis of other inherited DNA repair deficiencies such as Cockayne Syndrome (CS). Subsequent systematic studies revealed a litany of other characteristics that in general are connected or directly linked to ageing, including but not limited to early development of hearing loss, eye problems, fat redistribution, osteoporosis and neurodegeneration.

DNage has exclusive access to a number of different mouse models that exhibit diverse features and different rates of ageing or lifespan (in utero, 3 weeks, 2, 5, and 18 months), which can be specifically used for applied research like intervention studies with possible anti-aging compounds as well as for the identification of new targets and biomarkers for age-related diseases like osteoporosis and neurodegeneration.