The increased longevity in developed countries not necessarily goes hand in hand with amelioration of health and quality of life. Musculoskeletal, cardiovascular and neurodegenerative failure are not only hallmarks of the physical and cognitive decline in elderly people, but also represent common traits in several early-onset hereditary connective tissue (CT) disorders. These disorders represent a unique tool for the molecular investigation of such age-related pathologies due to the specific genetic disturbance of cellular homeostasis. The scientific objectives of CHANGE are: (i) to investigate CT disorders to identify key pathways responsible for age-related decline of physiological functions, being aware of gender differences (ii) to learn more about the interdependency of these pathways leading to stereotypic cellular responses including cellular senescence. This knowledge will pave the way for developing innovative treatment strategies for common diseases and frailty associated with ageing. To this end, we will train and establish a network of 10 highly-skilled doctoral candidates (DC) equipped with scientific expertise, transferable skills and societal and environment awareness as a foundation for their future careers. To succeed, CHANGE has built a unique and multidisciplinary network of 7 renowned academic partners and 5 companies (including 2 non-academics as associated partners) working together to train 10 young scientists. The DC network will address the basic biology of ageing from an interdisciplinary perspective, by deeply investigating CT diseases to uncover the pillars of ageing and its multi-systemic signatures. Altogether, CHANGE will provide an integrative map of cellular/extracellular consequences of age-related changes in cartilage, bone, muscle and vasculature as consequences to precocious disease exposure.

All chemicals whether they are drugs, cosmetics, agrochemicals or others need to be tested for their safety to man and the environment. The use of whole animal studies for the prediction of adverse effects in man, is problematic due to species dependent effects, high costs and a large burden to animals in terms of numbers and suffering. While there have been major improvements in human in vitro and in silico techniques, there is still a lack of an integrated risk assessment platform. The in3 proposal aims to significantly further the development of animal-free chemical and nanomaterial (NM) safety evaluation by creating a scientific and training program aimed at integrating human in vitro testing with computational approaches. The project will focus on human induced pluripotent stem cells (hiPSC) derived tissues, including liver, kidney, brain, lung and vasculature and to utilise mechanistic toxicology, quantitative adverse outcome pathways, biokinetics, cheminformatics and modelling approaches to derive testable prediction models. hiPSC present the major advantages provide non-cancerous derived tissues with identical genetic backgrounds. All Early Stage Researchers (ESRs) will work towards the same goal, utilising the same chemicals, donor cells, assays and software packages. All data will be centrally housed in standardised formats, appropriately annotated and linked with protocols and material information. While ESRs will hone their skills in their own field of expertise, they will also collaborate to create an in depth safety evaluation testing platform for the chosen test compounds. By interaction, problem solving, training and secondments over the three years, they will acquire a unique set of interdisciplinary skills for chemical and NM safety assessment. The project aims to accelerate the realisation of animal-free safety assessment and to graduate 15 PhD students with the ideal skill sets to carry out the strategy designed in in3 in the near future.