PRJNA793847
Increasing somatic mutation load in mice skeletal muscle reduces tissue function
As we age, our tissues undergo a progressive decline in function and regenerative capacity, which limits our physical performance and general health. Genomic instability is a hallmark of aging and is associated with somatic mutations. Somatic mutations accumulate continuously in post-zygotic cells, however it is still unclear if they contribute to age-related decline of tissue function. Here we developed a mouse model with accumulation of somatic mutations in muscle progenitor cells, and investigated the impact of increased somatic mutation load on regeneration after muscle injury, and on the functionality of the regenerated muscle tissue. Smaller size of muscle fibers and lower gain of muscle mass during regeneration indicated that muscle progenitors and derived myoblasts had a reduced ability to efficiently repair muscle injury. Furthermore, reduced grip strength demonstrated that the function of the whole skeletal muscle was impaired as a consequence. Similar to what is seen in the impaired aged skeletal muscle, the increased somatic mutation load in our mouse model affected skeletal muscle regeneration and function. Our data demonstrate that somatic mutation accumulation has a significant functional impact in somatic cells and contributes to the aging muscle phenotype.