A5006864561- Adipose Tissue and Metabolism
- Tryptophan and brain disorders
- Diet and metabolism studies
- Stress Responses and Cortisol
- Genetics, Aging, and Longevity in Model Organisms
- Frailty in Older Adults
- Nutrition and Health in Aging
- Growth Hormone and Insulin-like Growth Factors
- Mitochondrial Function and Pathology
- Birth, Development, and Health
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cancer-related cognitive impairment studies
- Circadian rhythm and melatonin
- Adipokines, Inflammation, and Metabolic Diseases
- Dietary Effects on Health
- Neonatal Respiratory Health Research
- Bipolar Disorder and Treatment
- Biomarkers in Disease Mechanisms
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Statistical Methods in Clinical Trials
- Intensive Care Unit Cognitive Disorders
- Autophagy in Disease and Therapy
- Metabolomics and Mass Spectrometry Studies
- Gut microbiota and health
Johns Hopkins University
2015-2024
Johns Hopkins Medicine
2015-2023
National Center for Geriatrics and Gerontology
2020
Southern Illinois University School of Medicine
2009-2013
Geriatric Research Education and Clinical Center
2013
Human and animal studies suggest that inflammation occurring outside the central nervous system (systemic inflammation) may play a key role in promoting neurodegeneration, Alzheimer's disease pathology, cognitive decline older adults. Systemic inflammation, which is marked by increased blood levels of circulating proinflammatory cytokines chemokines, occur as result events such infection, chronic disease, physical psychological stress, but also context these conditions subclinical processes...
The evolutionarily conserved target of rapamycin (TOR) signaling controls growth, metabolism, and aging. In the first robust demonstration pharmacologically-induced life extension in mammals, longevity was extended mice treated with rapamycin, an inhibitor mechanistic TOR (mTOR). However, detrimental metabolic effects treatment were also reported, presenting a paradox improved survival despite impairment. How lifespan such paradoxical unclear. Here we show that only observed during early...
Growth hormone (GH) signaling influences longevity in mice, with decreased GH associated longer life span and increased shortened span. A proposed mechanism through which postulates that lowers metabolic rate, thus slowing aging by decreasing production of damaging free radicals. The influence altered on metabolism was tested monitoring oxygen consumption (VO2), respiratory quotient (RQ), heat long-lived receptor knockout (GHRKO) Ames dwarf short-lived bovine GH-overexpressing transgenic...
We examine the impact of targeted disruption growth hormone-releasing hormone (GHRH) in mice on longevity and putative mechanisms delayed aging. GHRH knockout are remarkably long-lived, exhibiting major shifts expression genes related to xenobiotic detoxification, stress resistance, insulin signaling. These mutant also have increased adiponectin levels alterations glucose homeostasis consistent with removal counter-insulin effects hormone. While these overlap those caloric restriction, we...
Most mutations that delay aging and prolong lifespan in the mouse are related to somatotropic and/or insulin signaling. Calorie restriction (CR) is only intervention reliably increases longevity. There considerable phenotypic overlap between long-lived mutant mice normal on chronic CR. Therefore, we investigated interactive effects of CR targeted disruption or knock out growth hormone receptor (GHRKO) longevity signaling cascade. Every other day feeding corresponds a mild (i.e. 15%) which...
Mice with targeted deletion of the growth hormone receptor (GHRKO mice) are (GH) resistant, small, obese, hypoinsulinemic, highly insulin sensitive and remarkably long-lived. To elucidate unexpected coexistence adiposity improved sensitivity extended longevity, we examined effects surgical removal visceral (epididymal perinephric) fat on metabolic traits related to signaling longevity. Comparison results obtained in GHRKO mice normal animals from same strain revealed disparate (VFR) glucose...
Genetic suppression of insulin/insulin-like growth factor signaling (IIS) can extend longevity in worms, insects, and mammals. In laboratory mice, mutations with the greatest, most consistent, best documented positive impact on lifespan are those that disrupt hormone (GH) release or actions. These lead to major alterations IIS but also have a variety effects not directly related actions insulin insulin-like (IGF-1). Long-lived GH-resistant GHRKO mice targeted disruption GH receptor gene, as...
Chronic inflammation is associated with physical frailty and functional decline in older adults; however, the molecular mechanisms of this linkage are not understood. A mouse model chronic showed reduced motor function partial denervation at neuromuscular junction. Metabolomic profiling these mice further validation frail human subjects significant dysregulation tryptophan degradation pathway, including decreased serotonin, increased levels some neurotoxic kynurenines. In humans, kynurenine...
Abstract Tryptophan catabolism is highly conserved and generates important bioactive metabolites, including kynurenines, in some animals, NAD + . Aging inflammation are associated with increased levels of kynurenine pathway (KP) metabolites depleted , factors which implicated as contributors to frailty morbidity. Contrastingly, KP suppression supplementation life span animals. Here, we used DGRP_229 Drosophila elucidate the effects elevation, suppression, on physical performance...
Dysregulation of energy producing metabolic pathways has been observed in older adults with frailty. In this study, we used liquid chromatography-mass spectrometry technology to identify aging- and frailty-related differences metabolites involved glycolysis, the tricarboxylic (TCA) cycle, other metabolism-related serum a cohort community-dwelling aged 20-97 (n = 146). We also examined relationship between levels functional measures, physical frailty, risk status for adverse health outcomes....
Mitochondrial biogenesis is essential for cell viability. Growth hormone receptor knockout (GHRKO), calorie restriction, and surgical visceral fat removal constitute experimental interventions to delay aging increase life span. We examined the expression of known regulators mitochondriogenesis: peroxisome proliferator–activated γ co-activator 1α (PGC-1α), adenosine monophosphate (AMP)–activated protein kinase (AMPK), sirtuin-1 (SIRT-1) sirtuin-3 (SIRT-3), endothelial nitric oxide synthase...
Abstract Chronic inflammation (CI) in older adults is associated with reduced health span and life span. Interleukin-6 (IL-6) one CI marker that strongly adverse outcomes mortality aging. We have previously characterized a mouse model of frailty chronic inflammatory pathway activation (IL-10tm/tm, IL-10 KO) demonstrates the upregulation numerous proinflammatory cytokines, including IL-6. sought to identify more specific role for IL-6 within context aging developed targeted deletion both...
Mutations causing decreased somatotrophic signaling are known to increase insulin sensitivity and extend life span in mammals. Caloric restriction every other day (EOD) dietary regimens associated with similar improvements longevity normal mice; however, these interventions fail or growth hormone receptor knockout (GHRKO) mice. To investigate the interactions of GHRKO mutation caloric EOD interventions, we measured changes metabolic parameters oxygen consumption (VO2) respiratory quotient...
Interleukin 10tm1Cgn (IL 10tm) mice have been utilized as a model of chronic inflammation and declining health span because their propensity to develop activation in NFkB pathways, skeletal muscle cardiac changes, mitochondrial dysfunction. We hypothesized that older IL 10tm frail would alterations similar frail, humans measured parameters glucose metabolism, oxygen consumption (VO2), respiratory quotient (RQ), spontaneous locomotor activity, body composition plasma adipokine levels. To test...
Abstract The connection between aging‐related immune dysfunction and the lung manifestations of aging is poorly understood. A detailed characterization IL10‐deficient murine lung, a model accelerated frailty, reconciles features both immunosenescence in coherent model. Airspace enlargement developed middle‐aged (12 months old) aged (20–22 punctuated by an expansion macrophages alveolar cell apoptosis. Compared to wild‐type (WT) controls, lungs from young (4‐month‐old) mice showed increased...
Abstract Losartan is an oral antihypertensive agent that rapidly metabolized to EXP3174 (angiotensin-subtype-1-receptor blocker) and EXP3179 (peroxisome proliferator-activated receptor gamma [PPARγ] agonist), which was shown in animal studies reduce inflammation, enhance mitochondrial energetics, improve muscle repair physical performance. We conducted exploratory pilot study evaluating losartan treatment prefrail older adults (age 70–90 years, N = 25). Participants were randomized control...
Abstract Decline in neuromuscular function with aging is known to be a major determinant of disability and all‐cause mortality late life. Despite the importance problem, neurobiology age‐associated muscle weakness poorly understood. In previous report, we performed untargeted metabolomics on frail older adults discovered prominent alteration kynurenine pathway, route dietary tryptophan degradation that produces neurotoxic intermediate metabolites. We also showed pathway metabolites are...
Journal Article Metabolomics Captures the Biological Signatures of Aging and Health Span Identifies Pathway Targets for Intervention Get access Reyhan Westbrook, PhD, PhD Department Medicine, Division Geriatric Medicine Gerontology, The Johns Hopkins University School Baltimore, Maryland, USA Corresponding author, 5501 Bayview Circle, Rm 1A.62, MD 21224, USA. E-mail: rwestbr3@jhmi.edu Search other works by this author on: Oxford Academic PubMed Google Scholar Peter M Abadir, Journals...