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Salmon A.B.,Geriatric Research | Salmon A.B.,University of Texas Health Science Center at San Antonio
Antioxidants | Year: 2016

Despite numerous correlative data, a causative role for oxidative stress in mammalian longevity has remained elusive. However, there is strong evidence that increased oxidative stress is associated with exacerbation of many diseases and pathologies that are also strongly related to advanced age. Obesity, or increased fat accumulation, is one of the most common chronic conditions worldwide and is associated with not only metabolic dysfunction but also increased levels of oxidative stress in vivo. Moreover, obesity is also associated with significantly increased risks of cardiovascular disease, neurological decline and cancer among many other diseases as well as a significantly increased risk of mortality. In this review, we investigate the possible interpretation that the increased incidence of these diseases in obesity may be due to chronic oxidative stress mediating segmental acceleration of the aging process. Understanding how obesity can alter cellular physiology beyond that directly related to metabolic function could open new therapeutic areas of approach to extend the period of healthy aging among people of all body composition. © 2016 by the author; licensee MDPI, Basel, Switzerland.


Cole G.M.,University of California at Los Angeles | Frautschy S.A.,Geriatric Research
Journal of Nutrition | Year: 2010

The risk for dementia, a major contributor to incapacitation and institutionalization, rises rapidly asweage, doubling every 5 y after age 65. Tens of millions ofnewAlzheimer's disease (AD) and other dementia cases are projected as elderly populations increase around the world, creating a projected dementia epidemic for which most nations are not prepared. Thus, there is an urgent need for prevention approaches that are safe, effective, and affordable. This review addresses the potential of one promising candidate, the (n-3) fatty acid docosahexaenoic acid (DHA), which appears to slow pathogenesis of AD and possibly vascular dementia. DHA is pleiotropic, acting at multiple steps to reduce the production of the β-amyloid peptide, widely believed to initiate AD. DHA moderates some of the kinases that hyperphosphorylate the τ-protein, a component of the neurofibrillary tangle. DHA may help suppress insulin/neurotrophic factor signaling deficits, neuroinflammation, and oxidative damage that contribute to synaptic loss and neuronal dysfunction in dementia. Finally, DHA increases brain levels of neuroprotective brain-derived neurotrophic factor and reduces the (n-6) fatty acid arachidonate and its prostaglandin metabolites that have been implicated in promoting AD. Clinical trials suggest thatDHAor fish oil alone can slow early stages of progression, but these effects may be apolipoprotein E genotype specific, and larger trials with very early stages are required to prove efficacy.Weadvocate early intervention in a prodromal period with nutrigenomically defined subjects with an appropriately designed nutritional supplement, including DHA and antioxidants. © 2010 American Society for Nutrition.


Donskey C.J.,Geriatric Research | Donskey C.J.,Case Western Reserve University
American Journal of Infection Control | Year: 2013

Contaminated environmental surfaces provide an important potential source for transmission of health care-associated pathogens. In recent years, a variety of interventions have been shown to be effective in improving cleaning and disinfection of surfaces. This review examines the evidence that improving environmental disinfection can reduce health care-associated infections.


Taylor W.D.,Geriatric Research | Taylor W.D.,Vanderbilt University
New England Journal of Medicine | Year: 2014

A 74-year-old woman with hypertension that is well controlled with hydrochlorothiazide is brought by her daughter for an evaluation. The daughter states that her mother is withdrawn, often tearful, and at times appears to have memory problems but has no history of psychiatric illness. The patient is a retired teacher who is widowed and has lived independently for several years. During the last few months, she has stopped going to church and visiting friends. The patient's symptoms include irritability, anhedonia, fatigue, a 4.5-kg (10-lb) weight loss over a period of 3 months, and difficulty sleeping. She feels like a burden to her family. How should she be treated? Copyright © 2014 Massachusetts Medical Society.


Kripalani S.,Vanderbilt University | Theobald C.N.,Vanderbilt University | Anctil B.,Vanderbilt University | Vasilevskis E.E.,Vanderbilt University | Vasilevskis E.E.,Geriatric Research
Annual Review of Medicine | Year: 2014

New financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up) have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented; single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to postacute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, risk-stratification methods are available. Future work should better define the roles of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel. © 2014 by Annual Reviews. All rights reserved.


Azhar S.,Geriatric Research
Future Cardiology | Year: 2010

Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARα/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPAR (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. © 2010 Future Medicine Ltd.


Atri A.,Geriatric Research
The American journal of managed care | Year: 2011

Alzheimer's dementia represents organ failure of the brain. It denotes a clinical milestone that is the result of a pathological process, Alzheimer's disease (AD), which over 1 or more decades has wrought insidious destruction, and finally overwhelmed the brain's capacities to compensate. It is incurable, progressive, and follows an individual pace and course. AD is particularly demanding and devastating to family and caregivers, and patients, all of whom suffer psychologically and emotionally. The cholinesterase inhibitors (ChEIs) donepezil, galantamine, and rivastigmine and the N-methyl- D-aspartate receptor antagonist memantine are approved by the US Food and Drug Administration for AD; they are often used in combination once the disease reaches moderate stages. The relatively good safety profile of these medications, along with their efficacy in alleviating symptoms, is supported by several level-I evidence-grade, short-term, randomized, placebo-controlled trials (RCTs). However, these studies are of limited value in assessing the real-world clinical and economic impact of AD therapies. Long-term, observational studies can provide complementary information to results from short-term clinical trials and more accurately assess practical long-term benefits, risks, costs, and effects on clinically meaningful end points. There is now accumulating and convergent evidence from short- and long-term RCTs, longer-term open-label extensions of RCTs, and long-term observational studies that ChEIs and memantine reduce decline in cognition and daily function, and delay nursing home placement. Optimal care in AD is multifactorial; it includes early diagnosis and multidisciplinary care with educational and nonpharmacological interventions, while ensuring safety, treating comorbidities, caring for caregivers, and appropriate initiation and maintenance of combination therapy.


Morley J.E.,Saint Louis University | Morley J.E.,Geriatric Research
Family Practice | Year: 2012

Undernutrition in older persons usually presents as weight loss and is predominantly due to protein energy wasting. The presentation of undernutrition is often subtle in older persons and there is a need to utilize screening tools and increasing physician awareness. There are multiple treatable causes of undernutrition in older persons. The major causes are anorexia, cachexia, sarcopenia, dehydration, malabsorption and hypermetabolism. This article also provides an overview of the use of nutritional supplements and an approach to managing protein energy wasting. © The Author 2012. Published by Oxford University Press. All rights reserved.


Tennen R.I.,Stanford University | Chua K.F.,Stanford University | Chua K.F.,Geriatric Research
Trends in Biochemical Sciences | Year: 2011

Saccharomyces cerevisiae Sir2 is an NAD+-dependent histone deacetylase that links chromatin silencing to genomic stability, cellular metabolism and lifespan regulation. In mice, deficiency for the Sir2 family member SIRT6 leads to genomic instability, metabolic defects and degenerative pathologies associated with aging. Until recently, SIRT6 was an orphan enzyme whose catalytic activity and substrates were unclear. However, new mechanistic insights have come from the discovery that SIRT6 is a highly substrate-specific histone deacetylase that promotes proper chromatin function in several physiologic contexts, including telomere and genome stabilization, gene expression and DNA repair. By maintaining both the integrity and the expression of the mammalian genome, SIRT6 thus serves several roles that parallel Sir2 function. In this article, we review recent advances in understanding the mechanisms of SIRT6 action and their implications for human biology and disease. © 2010.


Wolden-Hanson T.,Geriatric Research
Interdisciplinary Topics in Gerontology | Year: 2010

Body composition changes over the lifespan of Brown Norway rats, in patterns similar to those of humans. Young adults are lean, with little fat, much of which is intra-abdominal. As they age, rats exhibit linear growth, and both lean and fat mass increase until late middle to early old age. Fat mass continues to accumulate throughout the lifespan, both viscerally and subcutaneously; aging animals carry a higher proportion of their fat mass peripherally. After middle age, skeletal muscle mass begins to decline, and sarcopenia develops when animals reach senescence. Finally, in late old age, or senescence, body weights begin to decline, and both fat and lean mass are lost. Healthy aged rats generally respond to negative energy balance challenges less robustly than younger adult animals, although they do appropriately regulate adipose tissue stores and preserve lean mass. The response to a positive energy balance challenge (high fat feeding) is less well regulated in aging animals, and dietary-induced obesity develops rapidly in aged animals. Here we present a summary of several studies of body composition in response to challenges of energy balance in aging male Brown Norway rats, with special emphasis on adipose tissue partitioning. Copyright © 2010 S. Karger AG, Basel.

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