Changes in Myofibril Size, Shape, and Network Connectivity in Aging Muscle

Across normal aging, striated muscles undergo structural remodeling associated with loss of force production. However, it is unknown how the organization of contractile myofibrillar networks, linked to their efficiency, is modified during aging. Using serial block-face scanning electron microscopy (SBF-SEM), we assess myofibril size, shape, and connectivity across different muscle types in young and geriatric mice and humans. Regardless of skeletal muscle fiber type in mice, age was associated with increased myofibrillar connectivity, with 24 months of age, as compared to 3 months, displaying more sarcomere branches. Distinctive age-related trends in myofibril size and shape were observed among each muscle type. Notably, there was a decrease in myofibril circularity from 3 months of age to 24 months of age in the gastrocnemius muscles of mice, contrasting with an increase in circularity in the soleus muscles during the same time frame. Additionally, while the soleus myofibrils in an aged cohort had a higher cross-sectional area, a reduction was observed in the gastrocnemius muscles. Cardiac muscles displayed no changes in sarcomere connectivity from 3 months to 24 months, although myofibril circularity and cross-sectional area were increased during this time. In human vastus lateralis muscles, sarcomere branching was positively correlated with advanced age. However, there were no consistent changes in myofibril size or shape across a wide age range from 16 to 68 years old. Overall, these data suggest that aging is associated with increased connectivity of the contractile networks within mammalian skeletal muscle.