268 results match your criteria: "Reynolds Oklahoma Center on Aging[Affiliation]"

Whole brain irradiation (WBI) therapy is an important treatment for brain metastases and potential microscopic malignancies. WBI promotes progressive cognitive dysfunction in over half of surviving patients, yet, the underlying mechanisms remain obscure. Astrocytes play critical roles in the regulation of neuronal activity, brain metabolism, and cerebral blood flow, and while neurons are considered radioresistant, astrocytes are sensitive to γ-irradiation.

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The anti-inflammatory effects of vagus nerve stimulation are well known. It has recently been shown that low-level, transcutaneous stimulation of vagus nerve at the tragus (LLTS) reduces cardiac inflammation in a rat model of heart failure with preserved ejection fraction (HFpEF). The mechanisms by which LLTS affect the central neural circuits within the brain regions that are important for the regulation of cardiac vagal tone are not clear.

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Cognitive impairment and dementia are major medical, social, and economic public health issues worldwide with significant implications for life quality in older adults. The leading causes are Alzheimer's disease (AD) and vascular cognitive impairment/dementia (VCID). In both conditions, pathological alterations of the cerebral microcirculation play a critical pathogenic role.

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Traumatic brain injury-induced cerebral microbleeds in the elderly.

Geroscience

February 2021

Department of Neurosurgery, University of Pecs, Medical School, 2 Ret Street, Pecs, 7624, Hungary.

Traumatic brain injury (TBI) was shown to lead to the development of cerebral microbleeds (CMBs), which are associated with long term cognitive decline and gait disturbances in patients. The elderly is one of the most vulnerable parts of the population to suffer TBI. Importantly, ageing is known to exacerbate microvascular fragility and to promote the formation of CMBs.

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Time-restricted feeding (TRF) for prevention of age-related vascular cognitive impairment and dementia.

Ageing Res Rev

December 2020

Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary; Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address:

Aging is the most significant risk factor for vascular cognitive impairment (VCI), and the number of individuals affected by VCI is expected to exponentially increase in the upcoming decades. Yet, there are no current preventative or therapeutic treatments available against the development and progression of VCI. Therefore, there is a pressing need to better understand the pathophysiology underlying these conditions, for the development of novel tools and interventions to improve cerebrovascular health and delay the onset of VCI.

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Increases in hypertension-induced cerebral microhemorrhages exacerbate gait dysfunction in a mouse model of Alzheimer's disease.

Geroscience

December 2020

Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Clinical studies show that cerebral amyloid angiopathy (CAA) associated with Alzheimer's disease (AD) and arterial hypertension are independent risk factors for cerebral microhemorrhages (CMHs). To test the hypothesis that amyloid pathology and hypertension interact to promote the development of CMHs, we induced hypertension in the Tg2576 mouse model of AD and respective controls by treatment with angiotensin II (Ang II) and the NO synthesis inhibitor L-NAME. The number, size, localization, and neurological consequences (gait alterations) of CMHs were compared.

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Defects in neuromuscular innervation contribute significantly to the age-related decline in muscle mass and function (sarcopenia). Our previous studies demonstrated that denervation induces muscle mitochondrial hydroperoxide production (HO and lipid hydroperoxides (LOOHs)). Here we define the relative contribution of mitochondrial electron transport chain (ETC) derived HO versus cytosolic phospholipase A (cPLA) derived LOOHs in neurogenic muscle atrophy.

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Companion animals likely do not spread COVID-19 but may get infected themselves.

Geroscience

October 2020

Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA.

Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From the epidemiological data, the picture emerges that the more severe etiopathologies among COVID-19 patients are found in elderly people. The risk of death due to COVID-19 increases exponentially with age.

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Aging is characterized by a chronic low-grade sterile inflammation dubbed as inflammaging, which in part originates from accumulating cellular debris. These, acting as danger signals with many intrinsic factors such as cytokines, are sensed by a network of pattern recognition receptors and other cognate receptors, leading to the activation of inflammasomes. Due to the inflammasome activity-dependent increase in the levels of pro-inflammatory interleukins (IL-1β, IL-18), inflammation is initiated, resulting in tissue injury in various organs, the brain and the spinal cord included.

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Brain metastases are life-threatening complications of triple-negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo and in vitro techniques and human samples, here we show that pericytes play crucial role in the development of metastatic brain tumors by directly influencing key steps of the development of the disease.

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The maintenance of skeletal muscle mass depends on the overall balance between the rates of protein synthesis and degradation. Thus, age-related muscle atrophy and function, commonly known as sarcopenia, may result from decreased protein synthesis, increased proteolysis, or simultaneous changes in both processes governed by complex multifactorial mechanisms. Growing evidence implicates oxidative stress and reactive oxygen species (ROS) as an essential regulator of proteolysis.

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Cracking the code on the innate immune program in OA.

Osteoarthritis Cartilage

May 2020

Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, 3000, Belgium; University Hospitals Leuven, Division of Rheumatology, Leuven, 3000, Belgium. Electronic address:

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Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain.

Geroscience

April 2020

Department of Biochemistry and Molecular Biology, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Vascular Cognitive Impairment and Neurodegeneration Program, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK, 73104, USA.

Age-related phenotypic changes of cerebromicrovascular endothelial cells lead to dysregulation of cerebral blood flow and blood-brain barrier disruption, promoting the pathogenesis of vascular cognitive impairment (VCI). In recent years, endothelial cell senescence has emerged as a potential mechanism contributing to microvascular pathologies opening the avenue to the therapeutic exploitation of senolytic drugs in preclinical studies. However, difficulties with the detection of senescent endothelial cells in wild type mouse models of aging hinder the assessment of the efficiency of senolytic treatments.

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Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood.

Geroscience

April 2020

Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA.

Aging-induced functional and phenotypic alterations of the vasculature (e.g., endothelial dysfunction, oxidative stress) have a central role in morbidity and mortality of older adults.

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Correlation network analysis shows divergent effects of a long-term, high-fat diet and exercise on early stage osteoarthritis phenotypes in mice.

J Sport Health Sci

March 2020

Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104, USA.

Background: Obesity increases knee osteoarthritis (OA) risk through metabolic, inflammatory, and biomechanical factors, but how these systemic and local mediators interact to drive OA pathology is not well understood. We tested the effect of voluntary running exercise after chronic diet-induced obesity on knee OA-related cartilage and bone pathology in mice. We then used a correlation-based network analysis to identify systemic and local factors associated with early-stage knee OA phenotypes among the different diet and exercise groups.

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CD82-TRPM7-Numb signaling mediates age-related cognitive impairment.

Geroscience

April 2020

Stephenson Cancer Center and Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA.

Aging is a crucial cause of cognitive decline and a major risk factor for Alzheimer's disease (AD); however, AD's underlying molecular mechanisms remain unclear. Recently, tetraspanins have emerged as important modulators of synaptic function and memory. We demonstrate that the level of tetraspanin CD82 is upregulated in the brains of AD patients and middle-aged mice.

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Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects.

Geroscience

April 2020

Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA.

Aging-induced structural and functional alterations of the neurovascular unit lead to impairment of neurovascular coupling responses, dysregulation of cerebral blood flow, and increased neuroinflammation, all of which contribute importantly to the pathogenesis of age-related vascular cognitive impairment (VCI). There is increasing evidence showing that a decrease in NAD availability with age plays a critical role in age-related neurovascular and cerebromicrovascular dysfunction. Our recent studies demonstrate that restoring cellular NAD levels in aged mice rescues neurovascular function, increases cerebral blood flow, and improves performance on cognitive tasks.

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Pharmacological or genetic depletion of senescent astrocytes prevents whole brain irradiation-induced impairment of neurovascular coupling responses protecting cognitive function in mice.

Geroscience

April 2020

Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 975 N. E. 10th Street - BRC 1303, Oklahoma City, OK, 731042, USA.

Article Synopsis
  • Whole brain irradiation (WBI) is a common treatment for brain metastases but can accelerate brain aging and cognitive decline in about 50% of patients, negatively impacting their quality of life.
  • This study investigates if WBI causes astrocyte senescence, leading to neurovascular coupling dysfunction and cognitive impairment.
  • Using a mouse model, researchers found that targeting and eliminating senescent astrocytes with senolytic drugs improved neurovascular function and cognitive performance after WBI, suggesting a potential therapeutic strategy.
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Objective: To stimulate future research directions that seek solutions for osteoarthritis (OA) at the interface between diverse disciplines and address osteoarthritis (OA) as a serious disease with a complexity that has presented a barrier to finding safe effective solutions.

Methods: Sessions were conducted at the 2019 meetings of the Orthopaedic Research Society (ORS) and Osteoarthritis Research Society International (OARSI) that included presentations and questions/comments submitted from leading OA researchers representing imaging, mechanics, biomarkers, phenotyping, clinical, epidemiology, inflammation and exercise.

Results: Solutions for OA require a paradigm shift in research and clinical methods in which OA is contextualized as a complex whole-body/person disease.

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Bring Back the Rat!

J Gerontol A Biol Sci Med Sci

February 2020

Department of Biology, College of Arts and Sciences, University of Alabama at Birmingham.

As 2020 is "The Year of the Rat" in the Chinese astrological calendar, it seems an appropriate time to consider whether we should bring back the laboratory rat to front-and-center in research on the basic biology of mammalian aging. Beginning in the 1970s, aging research with rats became common, peaking in 1992 but then declined dramatically by 2018 as the mouse became preeminent. The purpose of this review is to highlight some of the historical contributions as well as current advantages of the rat as a mammalian model of human aging, because we suspect at least a generation of researchers is no longer aware of this history or these advantages.

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Increases in sympathetic nerve activity (SNA) have been implicated in obesity-induced risk for cardiovascular diseases, especially hypertension. Previous studies indicate that oxidative stress in the rostral ventrolateral medulla (RVLM), a key brain stem region that regulates sympathetic outflow to peripheral tissues, plays a pathogenic role in obesity-mediated sympathoexcitation. However, the molecular mechanisms underlying this phenomenon are not clear.

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Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions.

Geroscience

December 2019

Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Aging of the microcirculatory network plays a central role in the pathogenesis of a wide range of age-related diseases, from heart failure to Alzheimer's disease. In the eye, changes in the choroid and choroidal microcirculation (choriocapillaris) also occur with age, and these changes can play a critical role in the pathogenesis of age-related macular degeneration (AMD). In order to develop novel treatments for amelioration of choriocapillaris aging and prevention of AMD, it is essential to understand the cellular and functional changes that occur in the choroid and choriocapillaris during aging.

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Astrocyte senescence contributes to cognitive decline.

Geroscience

February 2020

Vascular Cognitive Impairment and Neurodegeneration Program, and Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

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An age-associated increase in chronic, low-grade sterile inflammation termed "inflammaging" is a characteristic feature of mammalian aging that shows a strong association with occurrence of various age-associated diseases. However, the mechanism(s) responsible for inflammaging and its causal role in aging and age-related diseases are not well understood. Age-associated accumulation of damage-associated molecular patterns (DAMPs) is an important trigger in inflammation and has been proposed as a potential driver of inflammaging.

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17α-Estradiol promotes ovarian aging in growth hormone receptor knockout mice, but not wild-type littermates.

Exp Gerontol

January 2020

Faculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil. Electronic address:

Growth hormone receptor knockout mice (GHRKO) have reduced body size and increased insulin sensitivity. These mice are known for having extended lifespan, healthspan and female reproductive longevity. Seventeen α-estradiol (17α-E2) is reported to increase insulin sensitivity and extend lifespan in male mice, with less robust effects in female mice.

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