Final Activity Report Summary - AGING AND CANCER (Aging and Cancer) Aging is strongly correlated with a number of human diseases most prominently cancer and neurodegenerative diseases but also overall functional decline and frailty. This project aimed at investigating the involvement of biological mechanisms that prevent tumour formation in mammalian aging. The genome is under constant attack by a host of environmental and intrinsic genotoxic factors. Incorrect repair of DNA lesions leads to mutations, which when they occur in tumour suppressor genes or oncogenes can give rise to tumour formation. However, DNA damage has been shown to accumulate over the lifespan of mammals and is thought to contribute to cellular functionality that is characteristic for aging. Normally, DNA damage is repaired by a sophisticated network of various DNA repair systems. However, genetic defects in DNA repair pathways leads to accumulation of damages already early in life. Defects in transcription-coupled repair (TCR) lead to progeroid (premature aging-like) syndromes. In this project we have uncovered specific cellular responses to lesions that persist in TCR deficiencies. Intriguingly, these responses are associated with a shift from growth to somatic preservation, which is thought to promote lifespan extension and tumour suppression. We have suggested that this specific growth suppressive DNA damage response program might represent the culprit of the premature aging but cancer free outcome of progeroid TCR deficiencies.