Medicine and Health Sciences Commons^™

Impaired Skeletal Muscle Blood Flow Control With Advancing Age In Humans: Attenuated Atp Release And Local Vasodilation During Erythrocyte Deoxygenation, Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno

Health and Sport Science Faculty Publications

Rationale: Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.

Objective: To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation.

Methods and Results: We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, …

Protocol For A Randomized Controlled Trial Evaluating The Effect Of Physical Activity On Delaying The Progression Of White Matter Changes On Mri In Older Adults With Memory Complaints And Mild Cognitive Impairment: The Aibl Active Trial, E V Cyarto, N T Lautenschlager, P M Desmond, D Ames, C Szoeke, O Salvado, Matthew Sharman, Kathryn A Ellis, P M Phal, C L Masters, C C Rowe, Ralph Martins, Kay L Cox

Research outputs 2012

Background: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. …

Sarcopenia, Obesity, And Natural Killer Cell Immune Senescence In Aging: Altered Cytokine Levels As A Common Mechanism, Charles T. Lutz, Lebris S. Quinn

Pathology and Laboratory Medicine Faculty Publications

Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Epidemiological Characteristics And Underlying Risk Factors For Mortality During The Autumn 2009 Pandemic Wave In Mexico, Gerardo Chowell, Santiago Echevarria-Zuno, Cecile Viboud, Lone Simonsen, Mark A. Miller, Irma Fernandez-Garate, Cesar Gonzalez-Bonilla, Víctor H. Borja Aburto

Global Health Faculty Publications

Background

Elucidating the role of the underlying risk factors for severe outcomes of the 2009 A/H1N1 influenza pandemic could be crucial to define priority risk groups in resource-limited settings in future pandemics.

Methods

We use individual-level clinical data on a large series of ARI (acute respiratory infection) hospitalizations from a prospective surveillance system of the Mexican Social Security medical system to analyze clinical features at presentation, admission delays, selected comorbidities and receipt of seasonal vaccine on the risk of A/H1N1-related death. We considered ARI hospitalizations and inpatient-deaths, and recorded demographic, geographic, and medical information on individual patients during August-December, 2009. …

A Gutsy Way To Extend Longevity, Ryan P. Rogers, Blanka Rogina

UCHC Articles - Research

The studies conducted by Rera et al. successfully demonstrate a new role for dPGC-1 and mitochondrial biogenesis in ISC homeostasis and longevity. How does it all work? dPGC-1 overexpression increases levels of anti-oxidative enzymes to decrease oxidative damage and conserve ISC homeostasis. Preserved ISC homeostasis is required for gut maintenance, which is necessary for normal energy supply and/or prevention of microbial or toxin overload. All of these factors may contribute to delaying the onset of age related phenotypes. As Zhou et al. (2011) suggested, it is also possible that an unknown factor/s released by PGC-1 overexpression in ISCs/EBs regulates longevity …

The Six Dimensions Of Wellness And Cognition In Aging Adults, Kelley A. Strout, Elizabeth P. Howard

Nursing Faculty Scholarship

Objective: Examine how wellness in six dimensions (occupational, social, intellectual, physical, emotional, and spiritual) protects cognition in aging adults. Background: cognitive impairment increases with age. Baby boomers represent a significant percent of the population at risk for cognitive impairment. Cognitive impairment has a negative impact on nursing resources, health care finances, patient mortality, and quality of life. Wellness and prevention is one focus of Institute of Medicine’s vision for the future of nursing. Method: Literature was retrieved from Cumulative Index to Nursing and Allied Health Literature and MEDLINE. Research that examined the affect of wellness in each of the six …

Inhibition Of Soluble Tumor Necrosis Factor Ameliorates Synaptic Alterations And Ca2+ Dysregulation In Aged Rats, Diana M. Sama, Hafiz Mohmmad Abdul, Jennifer L. Furman, Irina A. Artiushin, David E. Szymkowski, Stephen W. Scheff, Christopher M. Norris

Graduate Center for Gerontology Faculty Publications

The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4-6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits …

Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, Srinivasarao Thulluri, Miaozong Wu, Eric R. Blough, Nandini D.P.K. Manne, Ashley B. Litchfield, Bin Wang

MIIR Faculty Research

Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase I (HOI), iron-regulatory protein I (IRPI), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model, …

Chronic Paracetamol Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fischer 344 X Brown Norway Rat Aorta, Kevin M. Rice, Sarath Meduru, Sunil K. Kakarla, Anjaiah Katta, Sriram P. Mupparaju, Brent Kidd, Lynne J. Goebel, Eric R. Blough

MIIR Faculty Research

Previous reports have demonstrated that increased levels of reactive oxygen species (ROS) and alterations in cell signaling characterize aging in the Fischer 344 X Brown Norway (FBN) rat aorta. Other work has suggested that increases in ROS may be related to vascular wall thickening and the development of hypertension. Paracetamol (acetaminophen) is a potent antioxidant that has been found to diminish free radicals in ischemia-reperfusion studies. However, it remains unclear whether chronic paracetamol administration influences signaling or ROS accumulation in the aging aorta. FBN rats (27 months old; n=8) were subjected to 6 months of treatment with a therapeutic dose …

Does Emotional Memory Enhancement Assist The Memory-Impaired?, Lucas S. Broster, Lee X. Blonder, Yang Jiang

Behavioral Science Faculty Publications

We review recent work on emotional memory enhancement in older adults and patients with mild cognitive impairment (MCI) or Alzheimer dementia (AD) and evaluate the viability of incorporating emotional components into cognitive rehabilitation for these groups. First, we identify converging evidence regarding the effects of emotional valence on working memory in healthy aging. Second, we introduce work that suggests a more complex role for emotional memory enhancement in aging and identify a model capable of unifying disparate research findings. Third, we survey the neuroimaging literature for evidence of a special role for the amygdala in MCI and early AD in …

Supraspinal Fatigue Impedes Recovery From A Low-Intensity Sustained Contraction In Old Adults, Tejin Yoon, Bonnie Schlinder-Delap, Manda L. Keller, Sandra K. Hunter

Exercise Science Faculty Research and Publications

This study determined the contribution of supraspinal fatigue and contractile properties to the age difference in neuromuscular fatigue during and recovery from a low-intensity sustained contraction. Cortical stimulation was used to evoke measures of voluntary activation and muscle relaxation during and after a contraction sustained at 20% of maximal voluntary contraction (MVC) until task failure with elbow flexor muscles in 14 young adults (20.9 ± 3.6 yr, 7 men) and 14 old adults (71.6 ± 5.4 yr, 7 men). Old adults exhibited a longer time to task failure than the young adults (23.8 ± 9.0 vs. 11.5 ± 3.9 min, …

Trpv1 Antagonists May Exacerbate Sepsis In Aged Mice: Should We Be Nervous?, Zenaide M.N. Quezado, Arpad Szallasi

Anesthesiology and Critical Care Medicine Faculty Publications

No abstract provided.

Neuroangiogenesis: A Vascular Basis For Alzheimer's Disease And Cognitive Decline During Aging, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Angiogenesis directs development of the brain's microcirculation during antenatal and postnatal development, but its role later in life is less well recognized. I contend that during senescence a reduced cerebral capillary density accounts in part for the vascular cognitive impairment observed in many older persons and possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age. To support this hypothesis I have examined the neurological literature for relevant studies on cerebral capillary density …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Vitamin D Mitigates Age-Related Cognitive Decline Through The Modulation Of Pro-Inflammatory State And Decrease In Amyloid Burden, Teresita L. Briones, Hala Darwish

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg …

Vision, Falls And Fear Of Falling In An Older Irish Population: Findings From The Irish Logitudinal Study On Aging (Tilda), E. Duggan, C. Finucane, H. Cronin, G. Savva, James Loughman, R. A. Kenny

Other

No abstract provided.

The Trajectories And Correlation Between Physical Limitation And Depression In Elderly Residents Of Beijing, 1992-2009, Xia Li, Wei Wang, Qi Gao, Lijuan Wu, Yanxia Luo, Zhe Tang, Xiuhua Guo

Research outputs 2012

Background Physical limitation and psychological distress have been reported to be related, but studies describing the change of instrumental activities of daily living (IADLs) and depression syndrome over time or exploring the link pattern for their development are limited. The study was to assess distinctive patterns for the development of physical limitation and depression and to explore their correlation to form a proper prevention strategy. Methods Dual trajectory analysis was conducted using data from the Beijing Longitudinal Study of Aging (BLSA) 1992–2009 hosted by Xuanwu hospital for subjects with full information on depression and physical limitation for all available visits. …

Predictors Of Rapid Cognitive Decline In Alzheimer's Disease: Results From The Australian Imaging, Biomarkers And Lifestyle (Aibl) Study Of Ageing, A Sona, P Zhang, D Ames, A I Bush, N T Lautenschlager, Ralph Martins, C L Masters, C C Rowe, C Szoeke, Kevin Taddei, Kathryn A Ellis

Research outputs 2012

Background: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients. Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as …

Altered Expression Of Alzheimer's Disease-Related Proteins In Male Hypogonadal Mice, Eleanor S. Drummond, Ralph Martins, D J Handelsman, A R Harvey

Research outputs 2012

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the …

Aging, Aerobic Activity And Interhemispheric Communication, Keith M. Mcgregor, Kenneth M. Heilman, Joe R. Nocera, Carolynn Patten, Todd M. Manini, Bruce Crosson, Andrew Butler

Physical Therapy Faculty Publications

Recent studies have shown that during unimanual motor tasks, aging adults show bilateral recruitment of primary motor cortex (M1), while younger adults show a suppression of the ipsilateral motor cortex. Additional work has indicated that increased bilateral M1 recruitment in older adults may be deleterious when performing some motor tasks. However, higher levels of physical fitness are associated with improved dexterity and fitness may mitigate the loss of both inhibitory and excitatory communication in aging adults. The goal of this study was to assess dexterity and interhemispheric motor communication in physically fit and sedentary middle-age (40–60 years) right handed participants …

Older Adults And Adults With Disabilities: Population And Service Use Trends In Maine, 2012 Edition, Julie T. Fralich Mba, Stuart Bratesman Mpp, Louise Olsen, Catherine Mcguire Bs, Jasper Ziller, Karen Mauney, Catherine Gunn

Disability & Aging

This Chartbook is an update to the Chartbook: Older Adults and Adults with Physical Disabilities: Population and Service Use Trends in Maine 2010. With the aging of Maine’s population and its status as the “oldest” state in the nation, the use of long term services continues to be a critical public policy issue in the State and nationally. The information in this Chartbook is provided to help inform state policy makers, legislators, providers, advocates and others with an interest in this subject.

Tp53 Codon 72 Polymorphism Affects Accumulation Of Mtdna Damage In Human Cells, Serena Altilia, Aurelia Santoro, Davide Malagoli, Catia Lanzarini, Josué Adolfo Ballesteros Álvarez, Gianluca Galazzo, Donald Carl Porter, Paolina Crocco, Giuseppina Rose, Giuseppe Passarino, Igor Roninson, Claudio Franceschi, Stefano Salvioli

Faculty Publications

Human TP53 gene is characterised by a polymorphism at codon 72 leading to an Arginine-to-Proline (R/P) substitution. The two resulting p53 isoforms have a different subcellular localisation after stress (more nuclear or more mitochondrial for the P or R isoform, respectively). p53P72 variant is more efficient than p53R72 in inducing the expression of genes involved in nuclear DNA repair. Since p53 is involved also in mitochondrial DNA (mtDNA) maintenance, we wondered whether these p53 isoforms are associated with different accumulation of mtDNA damage. We observed that cells bearing p53R72 accumulate lower amount of mtDNA damage upon rotenone stress with respect …

Aging, Neuromuscular Decline, And The Change In Physiological And Behavioral Complexity Of Upper-Limb Movement Dynamics, S. Morrison, K. M. Newell

Rehabilitation Sciences Faculty Publications

Aging is characterized by a general decline in physiological and behavioral function that has been widely interpreted within the context of the loss of complexity hypothesis. In this paper, we examine the relation between aging, neuromuscular function and physiological-behavioral complexity in the arm-hand effector system, specifically with reference to physiological tremor and isometric force production. Experimental findings reveal that the adaptive behavioral consequences of the aging-related functional decline in neurophysiological processes are less pronounced in simple motor tasks which provides support for the proposition that the motor output is influenced by both extrinsic (e.g., task related) and intrinsic (e.g., coordination, …