A5091649433- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Connexins and lens biology
- Sulfur Compounds in Biology
- Diet and metabolism studies
- Genetics, Aging, and Longevity in Model Organisms
- Metabolism and Genetic Disorders
- Biochemical effects in animals
- Redox biology and oxidative stress
- Aldose Reductase and Taurine
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Evolution and Genetic Dynamics
- interferon and immune responses
- Retinal Diseases and Treatments
- Advanced biosensing and bioanalysis techniques
- Inflammasome and immune disorders
- Diet, Metabolism, and Disease
- Cardiovascular Function and Risk Factors
- DNA Repair Mechanisms
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- Protein Interaction Studies and Fluorescence Analysis
- Adenosine and Purinergic Signaling
- Heme Oxygenase-1 and Carbon Monoxide
High Point University
2022-2024
Davidson College
2021-2024
Itron (United States)
2024
Clinical Research Consortium
2024
University of Washington
2019-2023
Seattle University
2020
Case Western Reserve University
2014-2017
Cornell University
2017
Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism and tissue dysfunction that occurs during aging. A thorough characterization age-associated mtDNA hampered by limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues an aged mouse cohort >89,000 independent show significant tissue-specific increases aging across all examined which did not correlate with content function. G→A/C→T...
Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment old with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. normalized increase proton leak reduced ROS cardiomyocytes from mice, accompanied by protein oxidation shift towards more thiol redox state hearts. Improved diastolic function was concordant increased phosphorylation cMyBP-C Ser282 but independent titin isoform shift....
Abstract The effects of two different mitochondrial‐targeted drugs, SS‐31 and NMN, were tested on Old mouse hearts. After treatment with the individually or Combined, heart function was examined by echocardiography. partially reversed an age‐related decline in diastolic while NMN fully deficiency systolic at a higher workload. Metabolomic analysis revealed that both Combined increased nicotinamide 1‐methylnicotinamide levels, indicating greater NAD + turnover, but only resulted significantly...
Aging muscle experiences functional decline in part mediated by impaired mitochondrial ADP sensitivity. Elamipretide (ELAM) rapidly improves physiological and function aging binds directly to the transporter ANT. We hypothesized that ELAM sensitivity leading rescued function. measured response stimulation young old mitochondria with treatment, vivo heart function, compared protein abundance, phosphorylation, S-glutathionylation of ADP/ATP pathway proteins. treatment increased increasing...
Mutations in mitochondrial DNA (mtDNA) cause maternally inherited diseases, while somatic mutations are linked to common diseases of aging. Although mtDNA impact health, the processes that give rise them under considerable debate. To investigate mechanism by which de novo arise, we analyzed distribution naturally occurring across mouse and human obtained Duplex Sequencing. We observe distinct mutational gradients G→A T→C transitions delimited light-strand origin Control Region (mCR). The...
Abstract The mitochondrial-rich renal tubule cells are key regulators of blood homeostasis via excretion and reabsorption metabolic waste. With age, tubules subject to increasing mitochondrial dysfunction declining nicotinamide adenine dinucleotide (NAD + ) levels, both hampering ATP production efficiency. We tested two interventions in young (6-mo) aged (26-mo) adult male mice: (ELAM), a tetrapeptide clinical trials that improves structure function, mononucleotide (NMN), an NAD intermediate...
Lens glutathione synthesis knockout (LEGSKO) mouse lenses lack de novo (GSH) but still maintain >1 mM GSH. We sought to determine the source of this residual GSH and mechanism by which it accumulates in lens.Levels GSH, disulfide (GSSG), GSH-related compounds were measured vitro vivo using isotope standards liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.Wild-type (WT) could accumulate from γ-glutamylcysteine glycine or intact LEGSKO only indicating that lens content is...
With an expanding aging population burdened with comorbidities, there is considerable interest in treatments that optimize health later life. Acarbose (ACA), a drug used clinically to treat type 2 diabetes mellitus (T2DM), can extend mouse life span greater effect males than females. Using genetically heterogeneous model, we tested the ability of ACA ameliorate functional, pathological, and biochemical changes occur during aging, determined which effects age were sex dependent. In both...
Purpose: To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. Methods: The transcriptome epithelia fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) buthionine sulfoximine (BSO)-treated mice compared to wild-type using RNA-Seq. Transcriptomic data were confirmed by qPCR Western blot/ELISA a subset genes. Results: RNA-Seq results in excellent agreement with (correlation coefficients...
Purpose: The purpose of this study was to present our hypothesis that aging alters metabolic function in ocular tissues. We tested the by measuring metabolism aged murine tissues alongside retinal responses light. Methods: Scotopic and photopic electroretinogram (ERG) young (3–6 months) (23–26 C57Bl/6J mice were recorded. Metabolic flux retina eyecup explants quantified using U-13C-glucose or U-13C-glutamine with gas chromatography-mass spectrometry (GC-MS), O2 consumption rate (OCR) a...
Abstract Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment old with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. normalized increase proton leak reduced ROS cardiomyocytes from mice, accompanied by protein oxidation shift towards more thiol redox state hearts. Improved diastolic function was concordant increased phosphorylation cMyBP-C Ser282 but independent titin...
Aging and poor diet are independent risk factors for heart disease, but the impact of high-sucrose (HS) consumption in aging is understudied. leads to impairments mitochondrial function that result muscle dysfunction (e.g., cardiac remodeling sarcopenia). We tested whether HS (60%kcal sucrose) would accelerate 24-month-old male CB6F1 mice. By week 1 on diet, mice developed significant hypertrophy compared age-matched chow-fed controls. The increased weight persisted throughout 4-week...
Aging muscle experiences functional decline in part mediated by impaired mitochondrial ADP sensitivity. Elamipretide (ELAM) rapidly improves physiological and function aging binds directly to the transporter ANT. We hypothesized that ELAM sensitivity leading rescued function. measured response stimulation young old mitochondria with treatment,
The ability to respond physical stress that disrupts normal physiological homeostasis at an older age embraces the concept of resilience aging. A stressor could be used induce responses are age-related, since declines with increasing age. Increased fat and sugar intake is a nutritional high prevalence obesity in people. In order determine effect this type diet on aging, 18-month-old C57BL/6J male mice were fed saturated (lard) sucrose (HFS) for ten months. At end 10-month study, HFS showed...
Abstract Patients with chronic anemia, or low blood hemoglobin levels, are frequently subjected to the cost, inconvenience, and discomfort of traditional hematology analyzer-based measurements levels via complete counts. Elimination need for count testing screening is an unmet clinical that we previously addressed by developing a non-invasive smartphone app estimates image analysis fingernail bed images. In this work, present additional data yielding significant improvement upon our...
Background The association between hyperuricemia and development of progressive chronic kidney disease has received increasing attention in recent years. Recent preclinical studies have shown that non–crystalline uric acid can induce renal-specific arteriolopathy, leading to renal injury tubulointerstitial inflammation. Methods We conducted a open-label cross-sectional study 25 patients with stage III (estimated glomerular filtration rate [eGFR], 7.0 mg/dL) levels serum acid. To determine...
Due to its unique spatiotemporal gradient of development, multiple regions extending from the lens nucleus can be collected observe distinct age-related changes in proteins early embryonic cells most recently differentiated fiber cells. In order better study protein across and their involvement cataract formation, methods that allow for reliable fractionation greater resolution are needed. Gentle stirring a SDS-containing dissolution buffer causes slough off at surface over time, allowing...
ABSTRACT Accumulation of somatic mutations in the mitochondrial genome (mtDNA) during aging has long been proposed as a possible mechanism and tissue dysfunction. A thorough characterization age-associated mtDNA hampered by limited ability to detect low frequency mutations. Here, we used Duplex Sequencing on eight tissues an aged mouse cohort >89,000 independent show significant tissue-specific increases across all examined which did not correlate with content function. G→A/C→T...
Abstract Background Mutations in the mitochondrial genome (mtDNA) can cause devastating maternally inherited diseases, while accumulation of somatic mtDNA mutations is linked to common diseases aging. Although impact human health, process(es) that give rise these are unclear and under considerable debate. We analyzed distribution naturally occurring across mouse obtained by Duplex Sequencing provide clues mechanism which de novo arise as well how replicated. Results observe two distinct...