Sarcopenia has long been recognized as a major cause of muscle strength loss in old age, however, the additional impact of immobilisation and re-training on muscle mass and architecture has not previously been investigated in elderly human individuals. Nine old men (age 61-74 yrs) and eleven young (age 21-27 yrs) underwent 2 weeks of unilateral whole leg casting followed by 4 weeks of re-training. Maximal voluntary contraction strength, neuromuscular activation, anatomical muscle cross sectional area, quadriceps muscle volume, muscle fibre pennation angle, physiological cross sectional area and specific force were assessed before, after immobilisation and again after re-training. Both old and young men experienced decreases in anatomical muscle cross sectional area, muscle fiber pennation angle, maximal voluntary contraction strength and specific force after 2 weeks of immobilisation (p<0.05). However, muscle fiber pennation angle and anatomical muscle cross sectional area were more reduced in young than old men (OM: – 4.7%, YM: -8.1%, p<0.05) and subsequent, re-training led to larger increases in anatomical muscle cross sectional area, quadriceps muscle volume and muscle fibre pennation angle (p<0.05) in young compared to old men. In contrast, quadriceps activation was reduced in old men after immobilisation (OM: – 9.9 %, p<0.05) while young men were unaffected (YM: -1.0 %, n.s.). The present study is the first to demonstrate that aging alters the neuromuscular response to short-term disuse and recovery in humans. Notably, immobilisation has a greater impact on the efferent neuronal function in old individuals, while young individuals were more affected at the muscle level. In addition, old individuals showed an attenuated response to re-training after immobilisation compared to young individuals.