Medicine and Health Sciences Commons^™

Deletion Of Sa Β-Gal+ Cells Using Senolytics Improves Muscle Regeneration In Old Mice, Cory M. Dungan, Kevin A. Murach, Christopher J. Zdunek, Zuo Jian Tang, Georgia L. Vonlehmden, Camille R. Brightwell, Zachary Hettinger, Davis A. Englund, Zheng Liu, Christopher S. Fry, Antonio Filareto, Michael Franti, Charlotte A. Peterson

Physical Therapy Faculty Publications

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl₂ or PBS 7- or 28 days prior to euthanization. Senescence-associated β-Galactosidase positive (SA β-Gal+) cell abundance was low in muscle from both young and old mice …

Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background

Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Methods and Results

Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients …

The Role Of Sirt1 In Skeletal Muscle Function And Repair Of Older Mice, Mathew J. Myers, Danielle L. Sheperd, Andrya J. Durr, David S. Stanton, Junaith S. Mohamed, John M. Hollander, Stephen E. Alway

Faculty & Staff Scholarship

Background Sirtuin 1 (SIRT1) is a NAD+ sensitive deacetylase that has been linked to longevity and has been suggested to confer beneficial effects that counter aging-associated deterioration. Muscle repair is dependent upon satellite cell function, which is reported to be reduced with aging; however, it is not known if this is linked to an aging-suppression of SIRT1. This study tested the hypothesis that Sirtuin 1 (SIRT1) overexpression would increase the extent of muscle repair and muscle function in older mice. Methods We examined satellite cell dependent repair in tibialis anterior, gastrocnemius, and soleus muscles of 13 young wild-type mice (20–30 …

Immunohistochemical Identification Of Human Skeletal Muscle Macrophages, Kate Kosmac, Bailey D. Peck, R. Grace Walton, Jyothi Mula, Philip A. Kern, Marcas M. Bamman, Richard A. Dennis, Cale A. Jacobs, Christian Lattermann, Darren L. Johnson, Charlotte A. Peterson

Physical Therapy Faculty Publications

Macrophages have well-characterized roles in skeletal muscle repair and regeneration. Relatively little is known regarding the role of resident macrophages in skeletal muscle homeostasis, extracellular matrix remodeling, growth, metabolism and adaptation to various stimuli including exercise and training. Despite speculation into macrophage contributions during these processes, studies characterizing macrophages in non-injured muscle are limited and methods used to identify macrophages vary. A standardized method for the identification of human resident skeletal muscle macrophages will aide in the characterization of these immune cells and allow for the comparison of results across studies. Here, we present an immunohistochemistry (IHC) protocol, validated by …

Oral Glucose Challenge Impairs Skeletal Muscle Microvascular Blood Flow In Healthy People, Ryan D. Russell, Donghua Hu, Timothy Greenaway, James E. Sharman, Stephen Rattigan, Stephen M. Richards, Michelle A. Keske

Health & Human Performance Faculty Publications and Presentations

Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). …

Metformin To Augment Strength Training Effective Response In Seniors (Masters): Study Protocol For A Randomized Controlled Trial, Douglas E. Long, Bailey D. Peck, Jenny L. Martz, S. Craig Tuggle, Heather M. Bush, Gerald Mcgwin, Philip A. Kern, Marcas M. Bamman, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background: Muscle mass and strength are strong determinants of a person’s quality of life and functional independence with advancing age. While resistance training is the most effective intervention to combat age-associated muscle atrophy (sarcopenia), the ability of older adults to increase muscle mass and strength in response to training is blunted and highly variable. Thus, finding novel ways to complement resistance training to improve muscle response and ultimately quality of life among older individuals is critical. The purpose of this study is to determine whether a commonly prescribed medication called metformin can be repurposed to improve the response to resistance …

Less Is More: The Physiological Basis For Tapering In Endurance, Strength, And Power Athletes, Kevin A. Murach, James R. Bagley

Physical Therapy Faculty Publications

Taper, or reduced-volume training, improves competition performance across a broad spectrum of exercise modes and populations. This article aims to highlight the physiological mechanisms, namely in skeletal muscle, by which taper improves performance and provide a practical literature-based rationale for implementing taper in varied athletic disciplines. Special attention will be paid to strength- and power-oriented athletes as taper is under-studied and often overlooked in these populations. Tapering can best be summarized by the adage “less is more” because maintained intensity and reduced volume prior to competition yields significant performance benefits.

Immune Function And Muscle Adaptations To Resistance Exercise In Older Adults: Study Protocol For A Randomized Controlled Trial Of A Nutritional Supplement, Richard A. Dennis, Usha Ponnappan, Ralph L. Kodell, Kimberly K. Garner, Christopher M. Parkes, Melinda M. Bopp, Kalpana P. Padala, Charlotte A. Peterson, Prasad R. Padala, Dennis H. Sullivan

Physical Therapy Faculty Publications

BACKGROUND: Immune function may influence the ability of older adults to maintain or improve muscle mass, strength, and function during aging. Thus, nutritional supplementation that supports the immune system could complement resistance exercise as an intervention for age-associated muscle loss. The current study will determine the relationship between immune function and exercise training outcomes for older adults who consume a nutritional supplement or placebo during resistance training and post-training follow-up. The supplement was chosen due to evidence suggesting its ingredients [arginine (Arg), glutamine (Gln), and β-hydroxy β-methylbutyrate (HMB)] can improve immune function, promote muscle growth, and counteract muscle loss. …