The Impact of Age and Frailty on Skeletal Muscle Autophagy Markers and Specific Strength: A Cross-sectional Comparison

Aging is associated with reduced specific strength, defined as strength normalized to the cross-sectional area of a given muscle or muscle group. Dysregulated autophagy, impairing removal of dysfunctional proteins and organelles, is suggested as one of the underlying mechanisms. The aim of this study was to investigate levels of autophagic markers in skeletal muscle in groups known to differ in specific strength. Sixty-two volunteers were assigned to the following study groups: young, old non-frail, old pre-frail, and old frail individuals. Leg lean mass was assessed with dual-energy X-ray absorptiometry and quadriceps femoris muscle strength by isometric maximal voluntary contraction. The abundance of autophagic proteins within skeletal muscle cytosolic and membrane sub-fractions were determined by western blotting. In addition, the level of heat shock proteins and proteins involved in the regulation of protein synthesis were measured. The abundance of LC3-I was higher in old frail compared to young individuals. If the three elderly groups were pooled, the level of LC3-II was higher in old compared to young subjects. Pre-frail and frail elderly also displayed higher levels of certain heat shock proteins. No between-group differences were observed for p62, LC3-II/LC3-I ratio, or any of the anabolic signaling molecules. A negative correlation was observed between cytosolic LC3-I and specific strength. Higher levels of LC3-I in the frail elderly might represent attenuated autophagosome formation. However, higher LC3-II levels indicate an increased abundance of autophagosomes. These findings may therefore imply that both the process of autophagosome formation and autophagosome-lysosome fusion are affected in frail elderly. Higher levels of heat shock proteins might represent an auto-protective mechanism against increased levels of misfolded proteins, possibly due to inefficient degradation. In conclusion, the reduction in specific strength with aging and frailty may partly be caused by alterations in muscle protein quality control.