Cholesterol conservation in skeletal muscle associated with age- and denervation-related atrophy

The lipid composition of muscles with age- and denervation-atrophy was assayed in whole muscle and isolated sarcolemma of rats aged 10 and 25 months. Although muscle mass decreased at least 17% during aging, muscle cholesterol concentration rose 15-20%. However, phospholipid concentrations were maintained; therefore, the cholesterol-to-phospholipid ratio increased during aging. Plasma cholesterol levels also rose 35%, but this could account for only about 10% of the age-related difference in muscle cholesterol. Likewise, following denervation (7 days) muscle mass decreased by at least 30%, but muscle cholesterol-to-phospholipid ratio increased; the magnitude of the denervation-induced response was unaffected by aging. To localize the source of cholesterol deposition during aging, these assays were repeated on isolated sarcolemma, sarcoplasmic reticulum, and mitochondria membrane fractions. Neither cholesterol nor phospholipid levels changed significantly with age in any of these major membrane systems. Furthermore, sarcolemmal fluidity, which depends on cholesterol content, did not vary significantly with age. At this level of resolution, it thus appears that skeletal muscle membrane phospholipid composition and fluidity do not change appreciably with age. Elevated cholesterol-to-phospholipid ratios detected in whole muscle may be due to cholesterol deposition in non-myofiber locations.