A5029299443- Osteoarthritis Treatment and Mechanisms
- Advanced MRI Techniques and Applications
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Cardiovascular Health and Disease Prevention
- Cardiovascular and exercise physiology
- Nutrition and Health in Aging
- Body Composition Measurement Techniques
- Advanced NMR Techniques and Applications
- Advanced Neuroimaging Techniques and Applications
- NMR spectroscopy and applications
- Cerebrovascular and Carotid Artery Diseases
- Diet and metabolism studies
- Lower Extremity Biomechanics and Pathologies
- Cardiac Ischemia and Reperfusion
- Knee injuries and reconstruction techniques
- Medical Image Segmentation Techniques
- Electron Spin Resonance Studies
- Muscle metabolism and nutrition
- Silk-based biomaterials and applications
- Proteoglycans and glycosaminoglycans research
- Biochemical effects in animals
- Neurological Disease Mechanisms and Treatments
- Peripheral Artery Disease Management
- Solid-state spectroscopy and crystallography
Institute on Aging
2010-2024
National Institute on Aging
2015-2024
National Institutes of Health
2015-2024
National Institute on Drug Abuse
2006-2021
Universidade Federal de São Paulo
2020
Johns Hopkins University
2016-2018
Johns Hopkins Medicine
2018
Towson University
2011
Tufts University
2011
Universidade de São Paulo
2011
Environmental stresses converge on the mitochondria that can trigger or inhibit cell death. Excitable, postmitotic cells, in response to sublethal noxious stress, engage mechanisms afford protection from subsequent insults. We show reoxygenation after prolonged hypoxia reduces reactive oxygen species (ROS) threshold for mitochondrial permeability transition (MPT) cardiomyocytes and survival is steeply negatively correlated with fraction of depolarized mitochondria. Cell exhibits a memory...
Abstract MR techniques are sensitive to the early stages of osteoarthritis, characterized by disruption collagen and loss proteoglycan (PG), but limited specificity. Here, water compartments in normal trypsin‐degraded bovine nasal cartilage were identified using a nonnegative least squares multiexponential analysis T 2 relaxation. Three components detected: 2,1 = 2.3 ms, 2,2 25.2 2,3 96.3 with fractions w 1 6.2%, 14.5%, 3 79.3%, respectively. Trypsinization resulted increased ( P < 0.01)...
Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration aged, but not young, mice resulted induction of rapid and lethal cytokine storm. found aging was accompanied by increases visceral fat similar to seen young obese (ob/ob or diet-induced [DIO]) mice. Yet, the effects obesity on inflammatory responses immunotherapeutics are well defined. determine adiposity IT tolerance aged compared with Both ob/ob- DIO-generated...
Skeletal muscle mitochondrial oxidative capacity declines with age and negatively affects walking performance, but the mechanism for this association is not fully clear. We tested hypothesis that impaired performance and, through mechanism, has a negative effect on speed. Muscle was measured by in vivo phosphorus magnetic resonance spectroscopy as postexercise phosphocreatine resynthesis rate, kPCr, 326 participants (154 men), aged 24–97 years (mean 71), Baltimore Longitudinal Study of...
Aerobic fitness and muscle bioenergetic capacity decline with age; whether such declines explain age-related slowing of walking speed is unclear. We hypothesized that energetics aerobic are independent correlates in simple challenging performance tests they account for the observed these same tests. Muscle bioenergetics was assessed as postexercise recovery rate phosphocreatine (PCr), kPCr, using phosphorus magnetic resonance spectroscopy (31P-MRS) 126 participants (53 men) Baltimore...
Aging is associated with distinct phenotypical, physiological, and functional changes, leading to disease death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, genetics. In this study, we conducted physiologic tests cross-sectionally throughout the entire lifespan male C57BL/6N mice. parallel, metabolomics analyses in serum, brain, liver, heart, skeletal muscle were also performed identify signatures frailty age-dependent...
Obesity is a top public health concern, and molecule that safely treats obesity urgently needed. Disulfiram (known commercially as Antabuse), an FDA-approved treatment for chronic alcohol addiction, exhibits anti-inflammatory properties helps protect against certain types of cancer. Here, we show in mice disulfiram prevented body weight gain abrogated the adverse impact obesogenic diet on insulin responsiveness while mitigating liver steatosis pancreatic islet hypertrophy. Additionally,...
Abstract Background Muscle mitochondrial dysfunction is associated with poor mobility in aging. Whether predicts subsequent decline unknown. Methods We examined 380 cognitively normal participants aged 60 and older (53%women, 22%Black) who were well‐functioning (gait speed ≥ 1.0 m/s) free of Parkinson's disease stroke at baseline had data on skeletal muscle oxidative capacity one or more assessments during an average 2.5 years. was measured by phosphorus magnetic resonance spectroscopy as...
A high-frequency dynamic nuclear polarization (DNP)/electron paramagnetic resonance spectrometer operating at 211 MHz for1H and 140 GHz forg= 2 centers (5 T static field) is described. The salient feature of the instrument a cyclotron-resonance maser (gyrotron) which generates high-frequency, high-power microwave radiation. This gyrotron, under conventional operation produces millisecond pulses kilowatt powers, has been adapted to operate ∼100 W for 1 20 s in continuous wave mode 10 power...
Cytochrome b5 reductases (CYB5R) are required for the elongation and desaturation of fatty acids, cholesterol synthesis mono-oxygenation cytochrome P450 enzymes, all which associated with protection against metabolic disorders. However, physiological role CYB5R in context metabolism, healthspan aging remains ill-defined. We generated CYB5R-overexpressing flies (CYB5R-OE) created a transgenic mouse line overexpressing CYB5R3 (CYB5R3-Tg) C57BL/6J background to investigate function this class...
Abstract We demonstrated that ATP synthase serves the functions of a primary mitochondrial K+ “uniporter,” i.e., way for to enter mitochondria. This entry is proportional synthesis, regulating matrix volume and energy supply-vs-demand matching. show can be upregulated by endogenous survival-related proteins via IF1. identified conserved BH3-like domain IF1 which overlaps its “minimal inhibitory domain” binds β-subunit F1. Bcl-xL Mcl-1 possess BH3-binding-groove engage exert effects,...
Abstract Diffusion‐tensor magnetic resonance imaging (DT‐MRI) offers objective measures of muscle characteristics, providing insights into age‐related changes. We used DT‐MRI to probe skeletal microstructure and architecture in a large healthy‐aging cohort, with the aim characterizing differences comparing these strength. recruited 94 participants (43 female; median age = 56, range 22–89 years) measured parameters—fractional anisotropy (FA) mean diffusivity (MD)—in 12 thigh muscles,...
Abstract INTRODUCTION Mitochondrial dysfunction is implicated in the pathophysiology of many chronic diseases. Whether it related to cognitive impairment and pathological markers unknown. METHODS We examined associations vivo skeletal muscle mitochondrial function (post‐exercise recovery rate phosphocreatine [kPCr] via magnetic resonance [MR] spectroscopy with future mild (MCI) or dementia, positron emission tomography (PET) blood biomarkers Alzheimer's disease [AD] neurodegeneration (i.e.,...
Administration of angiogenic factors stimulates neovascularization in ischemic tissues. However, there is no evidence that angiogenesis can be induced normoperfused skeletal muscles. We tested the hypothesis adenovirus-mediated intramuscular (IM) gene transfer 121-amino-acid form vascular endothelial growth factor (AdCMV.VEGF(121)) could stimulate nonischemic muscle and consequently attenuate hemodynamic deficit secondary to surgically ischemia.Rabbits rats received IM injections...
The distribution of cells within tissue-engineered constructs is difficult to study through nondestructive means, such as would be required after implantation. However, cell labeling with iron-containing particles may prove a useful approach this problem, because regions containing labeled have been shown readily detectable using magnetic resonance imaging (MRI). In study, we used the Food and Drug Administration-approved superparamagnetic iron oxide (SPIO) contrast agent Feridex in...
Whether individuals with insulin resistance (IR) but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research new therapeutics. We investigated 248 participants from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired associated prediabetes, IR, and duration severity hyperglycemia exposure. Mitochondrial was assessed as postexercise phosphocreatine recovery time constant (τPCr) by...
Abstract Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of has been linked a defect in neuromuscular control the pharynx. There no effective pharmacotherapy for OSA. objective this study was determine whether patency can be improved using chemogenetic approach deploying designer receptors exclusively activated drug (DREADD) hypoglossal motorneurons. DREADD...
The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects strength and physical performance. Factors that are associated this have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, predictive aging phenotypes such as cognitive impairment decline gait speed older adults. Therefore, we tested the hypothesis low LPC impaired capacity. Skeletal was measured using vivo phosphorus magnetic resonance...
Summary Calorie restriction ( CR ) is one of the most robust means to improve health and survival in model organisms. imposes a metabolic program that leads increased stress resistance delayed onset chronic diseases, including cancer. In rodents, induces upregulation two NADH ‐dehydrogenases, namely NAD (P)H:quinone oxidoreductase 1 Nqo1 cytochrome b 5 reductase 3 Cyb5r3 ), which provide electrons for energy metabolism. It has been proposed this may be responsible some beneficial effects ,...
Abstract ATP synthase (F1Fo) synthesizes daily our body's weight in ATP, whose production-rate can be transiently increased several-fold to meet changes energy utilization. Using purified mammalian F1Fo-reconstituted proteoliposomes and isolated mitochondria, we show F1Fo utilize both ΔΨm-driven H+- K+-transport synthesize under physiological pH = 7.2 K+ 140 mEq/L conditions. Purely K+-driven synthesis from single molecules measured by bioluminescence photon detection could directly...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTwo-dimensional solid-state proton NMR and exchangeLing Zheng, Kenneth W. Fishbein, Robert G. Griffin, Judith HerzfeldCite this: J. Am. Chem. Soc. 1993, 115, 14, 6254–6261Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://pubs.acs.org/doi/10.1021/ja00067a045https://doi.org/10.1021/ja00067a045research-articleACS PublicationsRequest reuse permissionsArticle...
Environmental stresses converge on the mitochondria that can trigger or inhibit cell death. Excitable, postmitotic cells, in response to sublethal noxious stress, engage mechanisms afford protection from subsequent insults. We show reoxygenation after prolonged hypoxia reduces reactive oxygen species (ROS) threshold for mitochondrial permeability transition (MPT) cardiomyocytes and survival is steeply negatively correlated with fraction of depolarized mitochondria. Cell exhibits a memory...