Aging is associated with a reduction in muscle mass and strength, which compromises functional independence. Skeletal muscle also shows an increase in mitochondrial dysfunction and oxidative stress in older adults. Resistance-exercise training is an important countermeasure for aging-associated muscle weakness. It has been shown that resistance-exercise training increases muscle strength and function in older adults, in association with a reduction in markers of oxidative stress and an improvement in mitochondrial function. Patients with sporadic mitochondrial cytopathies show an accumulation of mitochondrial DNA mutations and deletions in mature muscle, but not in satellite cells. Such patients have shown an activation of the satellite cells following myotoxic trauma and resistance, likely due to a fusion of the relatively quiescent satellite cells with mature muscle, which dilutes the mutational burden, a process called mitochondrial DNA shifting. Preliminary data strongly suggest that mitochondrial DNA shifting occurs in skeletal muscle from older adults following resistance-exercise training.