Biology subjects

Jorgenson, K. W.

Publications and source records attributed to Jorgenson, K. W..

3 recordsLinked to original sources

bioRxiv2025

Mechanical Loading Induces the Longitudinal Growth of Muscle Fibers via an mTORC1-Independent Mechanism

Mechanical loading drives skeletal muscle growth, yet the mechanisms that regulate this process remain undefined. Here, we show that an increase in mechanical loading induces muscle fiber growth through two distinct mechanisms. Radial growth, reflected by an increase in fiber cross-sectional area, is mediated through an mTORC1-dependent signaling pathway, whereas longitudinal growth, marked by the in-series addition of sarcomeres, is mediated through an mTORC1-independent signaling pathway. To gain further insight into the events that drive longitudinal growth, we combined BONCAT-based labeling of newly synthesized proteins with high-resolution imaging and determined that the in-series addition of sarcomeres is mediated by a process that involves transverse splitting at the Z-lines of pre-existing sarcomeres. Collectively, our findings not only challenge the long-standing view that mechanically induced growth is uniformly governed by mTORC1, but they also lay the framework for a new understanding of the molecular and structural events that drive this process. TeaserUnlocking the Mechanical Load-Induced Growth of Skeletal Muscle: mTORC1 Doesnt Always Hold the Key.

physiology↗

bioRxiv2023

A Novel Imaging Method (FIM-ID) Reveals that Myofibrillogenesis Plays a Major Role in the Mechanically Induced Growth of Skeletal Muscle

An increase in mechanical loading, such as that which occurs during resistance exercise, induces radial growth of muscle fibers (i.e., an increase in cross-sectional area). Muscle fibers are largely composed of myofibrils, but whether radial growth is mediated by an increase in the size of the myofibrils (i.e., myofibril hypertrophy) and/or the number of myofibrils (i.e., myofibrillogenesis) is not known. Electron microscopy (EM) can provide images with the level of resolution that is needed to address this question, but the acquisition and subsequent analysis of EM images is a time- and cost-intensive process. To overcome this, we developed a novel method for visualizing myofibrils with a standard fluorescence microscope (FIM-ID). Images from FIM-ID have a high degree of resolution and contrast, and these properties enabled us to develop pipelines for automated measurements of myofibril size and number. After extensively validating the automated measurements, we used both mouse and human models of increased mechanical loading to discover that the radial growth of muscle fibers is largely mediated by myofibrillogenesis. Collectively, the outcomes of this study offer insight into a fundamentally important topic in the field of muscle growth and provide future investigators with a time- and cost-effective means to study it.

cell biology↗

bioRxiv2021

Weight Pulling: A Novel Mouse Model of Human Progressive Resistance Exercise

This study describes a mouse model of progressive resistance exercise that utilizes a full-body/multi-joint exercise (weight pulling) along with a training protocol that mimics a traditional human paradigm (3 training sessions per week, [~]8-12 repetitions per set, 2 minutes of rest between sets, [~]2 maximal-intensity sets per session, last set taken to failure, and a progressive increase in loading that is based on the individuals performance). We demonstrate that weight pulling can induce an increase in the mass of numerous muscles throughout the body. The relative increase in muscle mass is similar to what has been observed in human studies, and it is associated with the same type of long-term adaptations that occur in humans (e.g., fiber hypertrophy, myonuclear accretion, and in some instances a fast-to-slow transition in Type II fiber composition). Moreover, we demonstrate that weight pulling can induce the same type of acute responses that are thought to drive these long-term adaptations (e.g., the activation of signaling through mTORC1 and the induction of protein synthesis at 1 hr post-exercise). Collectively, the results of this study indicate that weight pulling can serve as a highly translatable mouse model of progressive resistance exercise.

physiology↗