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

Abstract

Introduction Improved methods are needed to detect and quantify age‐related muscle change. In this study we assessed the electrical properties of muscle impacted by acquired mitochondrial DNA mutations via the PolG mouse, which exhibits typical age‐associated features, and the impact of a potential therapy, nicotinamide mononucleotide (NMN). Methods The gastrocnemii of 24 PolG and 30 wild‐type (WT) mice (8 PolG and 17 WT treated with NMN) were studied in an electrical impedance‐measuring cell. Conductivity and relative permittivity were determined from the impedance data. Myofiber cross‐sectional area (CSA) was quantified histologically. Results Untreated PolG mice demonstrated alterations in several impedance features, including 50‐kHz relative permittivity and center frequency. A potential effect of NMN was also observed in these parameters in PolG but not WT animals. Impedance values correlated with myofiber CSA. Discussion Electrical impedance is sensitive to myofiber features considered characteristic of aging and to the impact of a potential therapy.

Predicting myofiber cross‐sectional area and triglyceride content with electrical impedance myography: A study in db/db mice

“…Following ex vivo impedance measurements, GA muscles were fixed, sectioned, stained to identify myocyte cell membranes and nuclei, and the stained sections imaged and myofiber cross‐sectional area (CSA) determined as previously described 15 . On average, 300 myofibers (per WT muscle) and 375 myofibers (per db/db muscle) were counted per animal, for an average total number of 1487 myofibers for WT mice and 1867 myofibers for db/db mice at each timepoint.…”

“…Following ex vivo impedance measurements, GA muscles were fixed, sectioned, stained to identify myocyte cell membranes and nuclei, and the stained sections imaged and myofiber cross-sectional area (CSA) determined as previously described. 15 On average, 300 myofibers (per WT muscle) and 375 myofibers (per db/db muscle) were counted per animal, for an average total number of 1487 myofibers for WT mice and 1867 myofibers for db/db mice at each timepoint. We built separate models for predicting CSA and TG content for each EIM modality by implementing our previously adopted statistical approach 27,28 using the least absolute shrinkage and selection operator (LASSO) to perform a penalized regression procedure, coupled with a variable tuning parameter to avoid over-fitting 39 and select the most influential predictors.…”

Estimating myofiber cross‐sectional area and connective tissue deposition with electrical impedance myography: A study in D2‐mdx mice

“…The success of obtaining information about the impedance characteristics of muscle using EIM has been demonstrated in rodent models of injury, [36][37][38] inflammation, 39 aging, 27,30,40 and neuromuscular conditions, 41,42 and clinically during therapy trials in a variety of neuromuscular diseases (NMDs). 2,8,[43][44][45] Previous studies have also investigated relationships between impedance values and cell size and connective tissue deposition.…”

“…Samples were then embedded in paraffin blocks, sectioned into 10‐μm slices, and stained with anti–collagen VI antibody (Abcam ab6588) to identify the myocyte cell membranes and 4′,6‐diamidino‐2‐phenylindole (DAPI) to detect nuclei. The myofiber CSA was determined as described elsewhere 30 . Sections were imaged at 20× with an epifluorescence microscope (AxioImager M1; Carl Zeiss, Oberkochen, Germany) and myofiber area was measured using the muscle morphometry plug‐in (developed by A. Sinadinos using Eclipse IDE) in FIJI, the open source image processing software (ImageJ version 2.0.0‐rc‐68/1.52d; W.S.…”

Using Electrical Impedance Myography as a Biomarker of Muscle Deconditioning in Rats Exposed to Micro- and Partial-Gravity Analogs

“…Clearly there is a need for small, non-invasive diagnostic tools that will allow monitoring of muscle health and condition during all upcoming missions. Electrical impedance myography (EIM) is a technology that has been used in both pre-clinical (Li et al, 2016;Kapur et al, 2018b;Nagy et al, 2018;Clark-Matott et al, 2019;Mortreux et al, 2019d) and clinical studies (Spieker et al, 2013;Mcilduff et al, 2017;Rutkove et al, 2017;Sanchez and Rutkove, 2017a;Shefner et al, 2018). By applying a high-frequency, low-amplitude electrical current in the muscle and recording the resulting voltages, muscle quality can be assessed non-invasively (Sanchez and Rutkove, 2017b).…”