Electrical impedance myography detects age-related muscle change in mice

Abstract

Loss of muscle mass and strength represents one of the most significant contributors to impaired function in older adults. Convenient and non-invasive biomarkers are needed that can readily identify and track age-related muscle change. Previous data has suggested electrical impedance myography (EIM) has the potential to serve in this capacity. In this study we investigated how changes in EIM compared with other standard measures of muscle structure and function in aged compared with young mice. A total of 19 male mice aged approximately 25 months and 19 male mice aged 3 months underwent surface multifrequency EIM of the right gastrocnemius muscle using standard methods. Fore and hind limb grip strength, sciatic compound muscle action potential amplitude, and in-situ force of the gastrocnemius were also measured; after sacrifice, gastrocnemius myofiber size was assessed using standard histology. Spearman correlation coefficients were calculated to investigate the association between EIM and muscle characteristics. EIM in aged animals demonstrated significantly lower 50 kHz impedance phase (p<0.001) and reactance (p<0.01) values as well as reduced multifrequency parameters. In contrast, absolute gastrocnemius muscle mass was no different between young and aged mice (p = 0.58) but was reduced in aged mice after normalization to body mass (p<0.001). Median myofiber size in the aged mice was not different from that of young mice (p = 0.72). Aged mice showed reduced muscle function on the basis of normalized fore limb (p<0.001) and normalized hind limb (p<0.001) grip strength, as well as normalized gastrocnemius twitch (p<0.001) and normalized maximal isometric force (p<0.001). Sciatic compound muscle action potential amplitude was reduced in aged mice (p<0.05). EIM parameters showed good correlation with reduced standard physiological and electrophysiological measures of muscle health. Our study suggests that EIM is sensitive to aged-related muscle change and may represent a convenient and valuable method of quantifying loss of muscle health.

Altered muscle electrical tissue properties in a mouse model of premature aging

“…In agreement with a previous study that evaluated EIM in a group of live 3‐month‐old and 25‐month‐old C57/B6 mice and showed an increase in both longitudinal and transverse f c in the aged mice, in the present study we found a consistent increase in f c value in the untreated PolG mice, which correlates with the typical premature aging features associated with this model. Moreover, we also found that f c correlated with the differences in myofiber CSA observed in the PolG animals, unlike the previous work, which showed no significant differences in myofiber CSA between the 3‐ and 25‐month‐old groups.…”

“…Several previous studies have evaluated the technology for this purpose, including two studies in older adults 6,7 and one study in aged mice. 8 These studies have shown alterations in EIM parameters change over time consistent with aging-associated deterioration, and, in the case of the mouse study, correlation with functional measures and muscle mass. Nevertheless, additional measurements to support the value of EIM in this application are needed, especially in helping to explain the intrinsic alterations in EIM data and how they relate to myofiber health as well as whether they are responsive to a therapeutic intervention.…”

“…First, because tissue was only measured shortly after death, postmortem ischemia could have altered the impedance data as compared with living muscle . However, our previous work in both humans and mice support that these impedance alterations are also readily detectable using surface EIM methods . Second, our total sample numbers were small.…”

“…Major advantages of EIM over the other technologies just listed include potentially low cost, convenience, and high reproducibility. Several previous studies have evaluated the technology for this purpose, including two studies in older adults and one study in aged mice . These studies have shown alterations in EIM parameters change over time consistent with aging‐associated deterioration, and, in the case of the mouse study, correlation with functional measures and muscle mass.…”

Improved strength prediction combining clinically available measures of skeletal muscle mass and quality

“…17,33 Older age groups appear to experience functional changes, including reductions in strength and endurance, at rates that exceed those of decrements in muscle mass. 17,33 These differing rates of muscle senescence have been attributed to changes in tissue quality, a broadly applied term that includes loss of myofibers, 20 changes in the proportion of Type I and II fibres, 18 alterations in mitochondrial function, [34][35][36] changes in neural innervation, 37 inter-muscular adipose and connective tissue infiltration, 32,38,24,21 and relative increases in extracellular fluid. 21 Sarcopenia is thus a multidimensional condition that includes loss of muscle mass and changes in muscle quality that lead to functional deficits and ultimately to morbidity and mortality.…”