Age and diet alter skeletal muscle tubular aggregates

Tubular aggregates (TA's) may comprise the major histopathologic finding in hyperkalemic and normokalemic periodic paralysis. They also constitute a conspicuous morphologic abnormality in a number of myopathies, and have been associated with non-specific muscle myalgias/cramps. Caloric restriction (CR) is an experimental manipulation that increases longevity and reduces lesions in mice as compared to animals fed ad libitum (AL). However, the impact of CR on the dynamics of muscle tissue has not been previously established. In this paper we week to characterize the relationship between tubular aggregates and age and determine whether they are modulated by caloric restriction. We examined the effects of 40% caloric restriction (CR) on fiber damage formation in middle-aged (19 months of age) and older (27 months) mice. We also examined the effects of age and diet restriction on tubular aggregate formation in 12, 24, and 30 month old mice. Tissue blocks from the 19 and 27 month animals were also examined using electron microscopy for qualitative differences in tubular aggregates which may suggest a diet and age effect. There appeared to be no fiber or Z-disc damage attributable to age as assessed by quantitative light microscopy (LM). Age and diet had significant effects on the percent of fibers occupied by tubular aggregates. Qualitative LM revealed that many TA's may not have yet penetrated the sarcolemma in the young animals, and in particular, the young CR mice. The presence of round fibers was evident in the young CR mice whereas fibers were more angular in the AL mice. Fiber splitting was also evident in the CR mice, perhaps associated with new fiber formation. Other observations especially prevalent in mice with higher degrees of tubular aggregates included centrally displaced nuclei, nuclear chains among the sarcolemma borders, interfasicular wedging, longitudinally split fibers and cellular infiltrates. Electron microscopic examination of these areas revealed non distinction of the TA ultrastructure as a result of aging and diet. Large clusters of TA's were observed to be in close approximation with mitochondria and in some instances, mitochondria with internal vesicles were present. We conclude that diet restriction may reduce the accumulation of age-related tubular aggregates in skeletal muscle without altering their ultrastructure.