Recent studies have demonstrated that adult human tissues are a mosaic of genetically different cells. Evidence from blood genome analyses underline increased somatic variability in samples from old compared to young individuals, thus supporting the concept of progressive accumulation of mutations during a lifetime. Whether the same process might occur in tissues other than blood is currently unknown. However, age-related accumulation of mutations in human tissues could be envisaged as a major causative mechanism for tissue deterioration and functional impairment observed during human aging. To test this hypothesis, we plan to investigate somatic variability in a set of tissue biopsies from a group of young (<25 years) and a group of old (>65 years) people. In particular, we plan to analyse mutational load in clonally expanded single stem cells from muscle, fat, skin and kidney biopsies from the same individual. This technique will allow for the identification of single-cell specific variants in somatic tissues, and circumvent errors introduced during processing of libraries related to single-cell whole genome sequencing. The total number of mutations occurring per genome will be counted and we expect the old sample group to show an increased average number of mutations/genome compared to the young sample group. This will proof that somatic cells of different human tissues accumulate mutations during aging.