A5078520807- Muscle Physiology and Disorders
- Muscle metabolism and nutrition
- Adipose Tissue and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Nutrition and Health in Aging
- Diet and metabolism studies
- Tuberculosis Research and Epidemiology
- Exercise and Physiological Responses
- Antibiotic Resistance in Bacteria
- Mycobacterium research and diagnosis
- Metabolism, Diabetes, and Cancer
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- biodegradable polymer synthesis and properties
- Coenzyme Q10 studies and effects
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Cardiovascular and exercise physiology
- Biomedical Ethics and Regulation
- Multiple Myeloma Research and Treatments
- Vascular Tumors and Angiosarcomas
- Genetics and Physical Performance
- Adipokines, Inflammation, and Metabolic Diseases
- Bacterial Genetics and Biotechnology
- Acute Myeloid Leukemia Research
University of North Carolina at Chapel Hill
2024
University of Colorado Anschutz Medical Campus
2022-2023
Oklahoma Medical Research Foundation
2019-2020
Colorado State University
2016-2018
Metformin and exercise independently improve insulin sensitivity decrease the risk of diabetes. was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin antagonizes exercise-induced improvement in cardiorespiratory fitness. The purpose this study test hypothesis diminishes fitness after aerobic training (AET) by inhibiting skeletal muscle mitochondrial respiration protein synthesis older adults (62 ± 1 years). In double-blinded...
Abstract Background Successful strategies to halt or reverse sarcopenia require a basic understanding of the factors that cause muscle loss with age. Acute periods in older individuals have an incomplete recovery mass and strength, thus accelerating sarcopenic progression. The purpose current study was further understand mechanisms underlying failure old animals completely recover function after period hindlimb unloading. Methods Hindlimb unloading used induce atrophy Fischer 344–Brown...
The use of deuterium oxide (D2O) has greatly expanded the scope what is possible for measurement protein synthesis. greatest asset D2O labeling that it facilitates synthesis rates over prolonged periods time from single proteins through integrated tissue-based measurements. Because ease administration, method amenable in a variety models and conditions. Although adheres to same rules as other isotope methods, flexibility can create conditions are not approaches thus requires careful...
Abstract Aim Interventions that decrease atrophy during disuse are desperately needed to maintain muscle mass. We recently found massage as a mechanotherapy can improve regrowth following atrophy. Therefore, we aimed determine if has similar anabolic effects when applied normal weight bearing conditions (WB) or induced by hindlimb suspension (HS) in adult rats. Methods Adult (10 months) male Fischer344‐Brown Norway rats underwent either (HS, n = 8) WB (WB, for 7 days. Massage was using...
Abstract Epigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on sorting methods that can alter phenotype and introduce potential confounds. Here we demonstrate validate Nuclear Tagging Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling isolation ribosomes nuclei, thus RNA DNA, from central nervous system types. Analysis DNA modifications astrocytes or microglia the...
The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race in which competitors cycled for up to 24 h/day between altitudes of 1,675 and 4,025 m complete 800 km 21,000 elevation gain. In one athlete, we had the unique opportunity characterize skeletal muscle protein synthesis mitochondrial respiration response a normal activity control period (CON) CTR. We hypothesized that would be elevated maintained during extreme stresses Titrated bolus doses ADP were provided determine...
Abstract mTOR inhibition extends life span in multiple organisms. In mice, when metformin treatment (Met) is added to the inhibitor rapamycin (Rap), median and maximal extended a greater degree than with Rap or Met alone. Treatments that extend often maintain proteostasis. However, it less clear how individual tissues, such as skeletal muscle, proteostasis span–extending treatments. C2C12 myotubes, we used deuterium oxide (D2O) directly measure two primary determinants of proteostasis,...
A major reason that curing tuberculosis requires prolonged treatment is drug exposure changes bacterial phenotypes. The physiologic adaptations of
Abstract Treatment with the mechanistic target of rapamycin (mTOR) inhibitor, (RAP), alone and in combination antidiabetic drug, metformin (RAP+MET), extends lifespan mice. The mechanisms underlying extension are unclear. One possibility is improved capacity for proteostatic maintenance. We have previously characterized peripheral protein synthesis rates following treatment RAP. However, it unknown if RAP+MET elicits similar changes, or either affects brain. hypothesized that 8 weeks RAP...
The sigmoid E max model was used to describe the rRNA synthesis ratio (RS ratio) response of Mycobacterium tuberculosis antimicrobial concentration. RS-E measures maximal ability a drug inhibit RS and can be rank-order drugs based on their effect. RS-EC 90 is concentration needed achieve 90% , which may guide dose selection effect in vivo .
β-hydroxy β-methylbutyrate (HMB) is a nutritional supplement purported to enhance skeletal muscle mass and strength, as well cognitive function in older adults. The purpose of this study was determine the potential for long-term HMB supplementation preserve cognition aged mice, provide evidence link between vessel-associated pericyte outcomes. Four- (Adult/Ad) 17 month-old (Aged/Ag) C57BL/6J mice consumed chow containing 600 mg/kg BW/day either Ca-HMB (Ad, n=16; Ag, n=17) or Ca-Lactate 6...
Gemtuzumab ozogamicin (GO) is a CD33-targeting antibody-drug conjugate approved for the treatment of CD33-positive de novo and relapsed refractory acute myeloid leukemia (AML). Subset analyses have demonstrated improved clinical outcomes in patients with favorable-risk disease. It unclear whether addition GO to cytarabine anthracycline chemotherapy (7+3) improves compared other conventional regimens AML. We evaluated real-world experience added 7+3 favorable risk This retrospective analysis...
Transcriptome evaluation of Mycobacterium tuberculosis in the lungs laboratory animals during long-term treatment has been limited by extremely low abundance bacterial mRNA relative to eukaryotic RNA. Here we report a targeted amplification RNA sequencing method called SEARCH-TB. After confirming that SEARCH-TB recapitulates conventional RNA-seq vitro, applied tuberculosis-infected BALB/c mice treated for up 28 days with global standard isoniazid, rifampin, pyrazinamide, and ethambutol...
ABSTRACT A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual contributions the activity higher-order combinations. BALB/c mouse TB infection model was used evaluate each pairwise in clinically relevant Nix-TB regimen (bedaquiline-pretomanid-linezolid [BPaL]) during first three weeks treatment at human equivalent doses. RS ratio, an exploratory...
We have shown that the maintenance of skeletal muscle proteostasis is a shared characteristic in several animal models slowed aging. Loss satellite cell activity with advancing age has been correlated to impaired remodeling however emerging evidence suggests cells may not be requisite preventing age‐related changes muscle. It remains determined how recruitment influences protein turnover during advanced and after exercise. hypothesized will minimal contribution aging To test this hypothesis,...
The age-related loss of muscle mass and function are key contributors to the decline in healthspan. Maintenance protein homeostasis (proteostasis) is critical maintain quality during advancing age. We have previously shown that interventions slow aging increase ratio skeletal DNA synthesis, which we believe indicative improved proteostatic mechanisms. Oxidative stress inflammation blunt anabolic response feeding, thus supplementation with a nuclear factor, erythroid 2 like (Nrf2) activator...
Aging is associated with increases in oxidative stress. Redox imbalance occurs when production of reactive oxygen species (ROS) exceeds the capacity antioxidant enzymes to eliminate ROS. Increased levels intracellular ROS can compromise proteostasis by causing irreversible damage proteins. The transcription factor nuclear erythroid-derived 2-like 2 (Nrf2) mediates cellular endogenous defense system regulating that are cytoprotective against Nrf2 be activated phytochemically through...
The relationship between skeletal muscle mitochondrial respiration and development of chronic diseases is a highly contentious topic since assessment function varies across studies. PURPOSE: To determine if ex-vivo permeabilized fibers related to postprandial glucose tolerance in individuals at risk developing Type 2 Diabetes (T2D). METHODS: Participants (n=27; ≥55yrs), with impaired fasting (100-125 mg/dL), HbA1c (5.7-6.4%), (140-200 mg/dL) or family history T2D twice arrived overnight...
The anti‐hyperglycemic agent Metformin and exercise independently prevent the progression from prediabetes to overt type two diabetes (T2D) are both implicated in healthspan extension. However, emerging evidence indicates addition of may inhibit health benefits exercise. purpose current study was test hypothesis that blunts positive adaptations by inhibiting skeletal muscle mitochondrial fractional protein synthesis rates (FSR) respiration. Older adults (n=53, 62±5 yrs) with at least one...