Age-related structural changes show that loss of fibers is not a significant contributor to muscle atrophy in old mice

Age-related loss of skeletal muscle mass is widely considered a consequence of both fiber atrophy and fiber death. Evidence for fiber death derives largely from an age-related reduction in fiber numbers in muscle cross-sections, however it is unclear how age-related alterations in muscle morphology affect accuracy of such counts. To explore this we performed an examination of muscle and tendon length, muscle mass and girth, and pennation angle, in addition to histological section fiber counts of parallel-fibered (sternomastoid), fusiform (biceps brachii), and pennate (tibialis anterior, extensor digitorum longus, soleus) muscles from 31 mice aged 6-32 months. Age-related decline in mass and girth occurred in soleus (p = 0.026; p = 0.040), tibialis anterior (p = 0.004; p = 0.039), and extensor digitorum longus (p = 0.040; p = 0.022) muscles, for which location of maximal girth also changed. Tendon length and pennation angle remained consistent across the lifespan in all except soleus which showed elongation of both proximal and distal tendons coupled with alterations in pennation angle. Age-related decreases in fiber number were observed in transversely sectioned soleus and extensor digitorum longus muscles however when age-related changes in morphology were accounted for via oblique sectioning the age-related decrease in fiber number was eliminated. Findings show loss of fibers is not a significant contributor to agerelated muscle wasting in mice, and that age-related changes in connective tissue selectively impact muscle structure. Fiber shortening is a likely contributor to loss of mass and change in function in muscles of old mice.

Automated summary

Age-related loss of skeletal muscle mass in mice is mainly due to fiber shortening rather than fiber loss, with alterations in muscle morphology playing a significant role in muscle wasting. Tendon length and pennation angle remain consistent across the lifespan, while changes in connective tissue selectively impact muscle structure.