A5014120435- Frailty in Older Adults
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Dietary Effects on Health
- Nutrition and Health in Aging
- Hip and Femur Fractures
- Diet and metabolism studies
- Resilience and Mental Health
- Tryptophan and brain disorders
- Birth, Development, and Health
- Genetics, Aging, and Longevity in Model Organisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Circadian rhythm and melatonin
- Heart Rate Variability and Autonomic Control
- Cancer, Lipids, and Metabolism
- Health, Environment, Cognitive Aging
- HIV-related health complications and treatments
- HIV/AIDS Research and Interventions
- Spaceflight effects on biology
- Cytomegalovirus and herpesvirus research
- Stress Responses and Cortisol
- Nutritional Studies and Diet
- Adipokines, Inflammation, and Metabolic Diseases
Duke University
2017-2024
Duke Medical Center
2019
Geriatric Research Education and Clinical Center
2018
University of North Carolina at Chapel Hill
2009-2012
Eastern Virginia Medical School
2011-2012
Histone deacetylases (HDACs) act on histones within the nucleosome-bound promoter of human immunodeficiency virus type 1 (HIV-1) to maintain proviral latency. HDAC inhibition leads expression and escape HIV from We evaluated ability potent inhibitor recently licensed for use in oncology, suberoylanilide hydroxamic acid (SAHA; Vorinostat), selective Class I HDACs, induce cell lines production resting CD4(+) T cells antiretroviral-treated, aviremic HIV-infected patients. In J89, a Jurkat line...
The geroscience hypothesis proposes that therapy to slow or reverse molecular changes occur with aging can delay prevent multiple chronic diseases and extend healthy lifespan
Studying the effects of early HIV infection on human antibody responses, M. Anthony Moody and colleagues find rapid polyclonal B cell differentiation structural damage to gut-associated lymphoid tissue.
Background Human immunodeficiency virus (HIV) infection that persists despite antiretroviral therapy (ART) is a daunting problem. Given the limited evidence resting CD4+ T cell (RCI) affected by histone deacetylase (HDAC) inhibitor valproic acid (VPA), we measured stability of RCI and residual viremia in patients who added VPA with or without raltegravir (RAL), enfuvirtide (ENF) VPA, to standard ART. Methods Patients plasma HIV RNA<50 c/mL sustained-release (Depakote ER®) twice daily, RAL...
For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems be true new emerging metabolic identified by innovative technological advances. Further, ever evolving evidence of differential responses lifestyle interventions sex and body compositions the range. In secondary analysis, we had opportunity test these principles newly molecular...
ABSTRACT Despite successful antiretroviral therapy (ART), low-level viremia (LLV) may be intermittently detected in most HIV-infected patients. Longitudinal blood plasma and resting CD4 + T cells were obtained from two patients on suppressive ART to investigate the source of LLV. Single-genome sequencing HIV-1 env LLV was performed, sequences compared recovered limiting-dilution outgrowth assays cells. The circulating virus clone identical pools millions Understanding sources requires...
Abstract Quantification of biological aging has been proposed for population surveillance age-related decline in system integrity and evaluation geroprotective therapies. However, methods quantifying have little studied geriatric populations. We analyzed three clinical-biomarker-algorithm to quantify aging. Klemera–Doubal method Biological Age homeostatic dysregulation algorithms were parameterized from analysis U.S. National Health Nutrition Examination Surveys (NHANES) data (N = 36,207)...
Objective Alterations of the immune system play important roles in Alzheimer's disease (AD). The primary purpose this study was to compare plasma levels neopterin, a marker cellular activity, amnestic mild cognitive impairment (aMCI), early (mild moderate) AD, and cognitively normal controls. In addition, correlation neopterin with interferon‐gamma (IFN‐γ) interleukin‐6 (IL‐6) also examined. Methods Plasma samples from patients mild‐to‐moderate AD ( N = 34), aMCI 27), controls 30) were...
BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported alterations in a monocyte metabolism transcriptional network (CMTN) - suggestive of cellular were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought determine whether the CMTN independently predict incident prediabetes/T2D risk, correlate accumulation.METHODSMonocyte mRNA expression 11 genes was quantified among 934 Multi-Ethnic Study...
Abstract Exercise provides a wide range of health‐promoting benefits, but support is limited for clinical programs that use exercise as means health promotion. This stands in contrast to restorative or rehabilitative exercise, which considered an essential medical service. We propose there place ongoing, structured wellness and promotion programs, with the primary therapeutic focus. Such have long‐lasting are easily implementable, associated high levels participant satisfaction. describe...
OBJECTIVES Defining common patterns of recovery after an acute health stressor (resiliency groups) has both clinical and research implications. We sought to identify groups patients with similar across 10 outcomes following hip fracture (stressor) determine the most important predictors resiliency group membership. DESIGN Secondary analysis three prospective cohort studies. SETTING Participants were recruited from various hospitals in Baltimore Hip Studies network followed for up 1 year...
Abstract Background Older adults with similar health conditions often experience widely divergent outcomes following stressors. Variable recovery after a stressor may be due in part to differences biological mechanisms at the molecular, cellular, or system level, that are elicited response We describe PRIME‐KNEE study as an example of ongoing research validate provocative clinical tests and biomarkers predict resilience specific Methods is ongoing, prospective cohort will enroll 250 ≥60...
Abstract Background Clinically similar older adults demonstrate variable responses to health stressors, heterogeneity attributable differences in physical resilience. However, molecular mechanisms underlying resilience are unknown. We previously derived a measure of after hip fracture—the expected recovery differential (ERD)—that captures the difference between actual and predicted recovery. Starting with biomarkers associated performance, morbidity, mortality, fracture, we evaluated...
miRNAs are small noncoding RNAs that may contribute to common diseases through epigenetic regulation of gene expression. Little is known regarding the role in type 2 diabetes (T2D). We performed miRNA sequencing and transcriptomic profiling peripheral monocytes from longitudinal Multi-Ethnic Study Atherosclerosis (MESA) (N = 1,154). examined associations between prevalent impaired fasting glucose T2D evaluated T2D-associated effect on incident T2D. Of 774 detected miRNAs, 6 (miR-22-3p,...
The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk Alzheimer's disease related dementias (ADRD).The objective this study was to determine the associations plasma KP (kynurenine [KYN], kynurenic acid [KA], tryptophan [TRP]) panel ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], neurofilament light [NfL]) in subset older adults...
Aging is characterized by deleterious immune and metabolic changes, but the onset of these changes unknown. We measured biomarkers in adults beginning at age 30. To our knowledge, this first study to evaluate aged 30 over 80. Biomarkers were quantified 961 adults. Tumor necrosis factor alpha (TNF-α), tumor receptor I (TNFR-I), II (TNFR-II), interleukin (IL)-2, IL-6, VCAM-I, D-Dimer, G-CSF, regulated on activation, normal T cell expressed secreted (RANTES), matrix metalloproteinase-3 (MMP-3),...
ABSTRACT Calorie restriction (CR) slows aging and increases healthy lifespan in model organisms. We tested if CR slowed biological humans using DNA methylation analysis of blood samples from N=197 participants the Comprehensive Assessment Long-term Effects Reducing Intake Energy (CALERIE™) randomized controlled trial. quantified effects on by comparing change scores for six epigenetic-clock Pace-of-Aging measures between n=128 CR-group n=69 ad-libitum-control-group at 12- 24-month...
<h2>Summary</h2><h3>Background</h3> The hard endpoint of death is one the most significant outcomes in both clinical practice and research settings. Our goal was to discover direct causes longevity from medically accessible data. <h3>Methods</h3> Using a framework that combines local causal discovery algorithms with maximally predictive compact feature sets (the "Markov boundaries" response) equivalence classes, we examined 186 variables their relationships survival over 27 years 1507...
Circadian misalignment, as occurs in shiftwork, is associated with numerous negative health outcomes. Here, we sought to improve data labeling accuracy from wearable technology using a novel pre-processing algorithm 27 police trainees during shiftwork. Secondarily, explored changes four metabolic salivary biomarkers of circadian rhythm Using two-group observational study design, participants completed in-class training dayshift for 6 weeks followed by either or nightshift field-training...
Some human studies have identified infection with cytomegalovirus (CMV), a member of the alpha herpesvirus family, as risk factor for Alzheimer's disease and related dementias (ADRD). To our knowledge, no evaluated associations CMV seropositivity plasma biomarkers ADRD in middle-aged adults.
Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer’s disease (AD). The retina vitreous shown measurable quantities phosphorylated tau 181 (p-tau181). aqueous humor, which can be collected during cataract surgery, may concentrations p-tau181. Objective: To determine whether is detectable in the humor if so, it other measures that might consistent AD such as higher plasma concentration lower Montreal Cognitive Assessment (MoCA-BLIND version...
Although both exercise and thyroid hormone (TH) status can cause cellular metabolic changes in skeletal muscle, the impact of TH on exercise-associated is not well understood. Here, we examined effects muscle fiber type, cell signaling, metabolism a rabbit model training — chronic motor nerve stimulation (CMNS). Five rabbits were rendered hypothyroid for seven to eight weeks three made hyperthyroid two prior CMNS left peroneal ten days. We then measured protein markers autophagy, nutrient-...
For some years, a prevalent view in immunochemistry was to regard the riddle of antibody specificity as entirely dependent on solution problem specific labeling active sites. The direct approach sites has proved feasible and yield significant information from this source promises increase. However, study may for present be viewed complementing extensive work myeloma other immunoglobulin sequences. From these models are derived most our current insights into nature variability.