The human ageing process is associated with a significant decline in skeletal muscle mass and muscle strength. This progressive loss in muscle mass and strength, known as sarcopenia, disturbs the daily life of elderly and may hinder healthy ageing. As it has been reported that a number of saropenia-related phenotypes are highly heritable, it is important to understand how ageing and its interactions with lifestyle and genetic factors affect physical fitness. The following doctoral project therefore aims at developing a better understanding regarding the effects of genotypic sequence, structural variation and physical activity on muscle mass decline and loss in muscle strength over a ten-year period(2002-2006 > 2012-2015). In the first study, a Genetic Predisposition Score (GPS) based on a number of sequence variants in candidate genes will be used to predict the loss of muscle strength with ageing. The secondstudy will examine the epigenetic changes in promoter regions of candidate genes, occurring under the influence of physical activity. In conclusion, it is our purpose to determine whether the loss in muscle functionand muscle mass, occurring with ageing, is (epi-)genetically determined.