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Chumlea W.C.,Wright State University | Chumlea W.C.,French Institute of Health and Medical Research | Cesari M.,French Institute of Health and Medical Research | Evans W.J.,Glaxosmithkline | And 5 more authors.
Journal of Nutrition, Health and Aging | Year: 2011

Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x-ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength. © 2011 Serdi and Springer Verlag France.

Bebenek I.G.,University of California at Los Angeles | Hernandez-Pando R.,National Institute of Medical science and Nutrition | Chi L.,University of California at Los Angeles | Riedl M.,University of California at Los Angeles | And 8 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

Background: New therapies are necessary to address inadequate asthma control in many patients. This study sets out to investigate whether hypoxia-inducible factor (HIF) is essential for development of allergic airway inflammation (AAI) and therefore a potential novel target for asthma treatment. Methods: Mice conditionally knocked out for HIF-1β were examined for their ability to mount an allergic inflammatory response in the lung after intratracheal exposure to ovalbumin. The effects of treating wild-type mice with either ethyl-3,4-dihydroxybenzoate (EDHB) or 2-methoxyestradiol (2ME), which upregulate and downregulate HIF, respectively, were determined. HIF-1α levels were also measured in endobronchial biopsies and bronchial fluid of patients with asthma and nasal fluid of patients with rhinitis after challenge. Results: Deletion of HIF-1β resulted in diminished AAI and diminished production of ovalbumin-specific IgE and IgG1. EDHB enhanced the inflammatory response, which was muted upon simultaneous inhibition of vascular endothelial growth factor (VEGF). EDHB and 2ME antagonized each other with regard to their effects on airway inflammation and mucus production. The levels of HIF-1α and VEGF increased in lung tissue and bronchial fluid of patients with asthma and in the nasal fluid of patients with rhinitis after challenge. Conclusions: Our results support the notion that HIF is directly involved in the development of AAI. Most importantly, we demonstrate for the first time that HIF-1α is increased after challenge in patients with asthma and rhinitis. Therefore, we propose that HIF may be a potential therapeutic target for asthma and possibly for other inflammatory diseases. © 2011 John Wiley & Sons A/S.

Tolea M.I.,University of Missouri-St. Louis | Costa P.T.,Laboratory of Cognition and Personality | Terracciano A.,Laboratory of Cognition and Personality | Ferrucci L.,Clinical Research Branch | And 4 more authors.
Journals of Gerontology - Series B Psychological Sciences and Social Sciences | Year: 2012

Objectives.The objective of this study was to explore the associations between openness to experience and conscientiousness, two dimensions of the five-factor model of personality, and usual gait speed and gait speed decline.Method.Baseline analyses were conducted on 907 men and women aged 71-82 years participating in the Cognitive Vitality substudy of the Health, Aging, and Body Composition study. The longitudinal analytic sample consisted of 740 participants who had walking speed assessed 3 years later.Results.At baseline, gait speed averaged 1.2 m/s, and an average decline of 5% over the 3-year follow-up period was observed. Higher conscientiousness was associated with faster initial walking speed and less decline in walking speed over the study period, independent of sociodemographic characteristics. Lifestyle factors and disease status appear to play a role in the baseline but not the longitudinal association between conscientiousness and gait speed. Openness was not associated with either initial or decline in gait speed.Discussion.These findings extend the body of evidence suggesting a protective association between conscientiousness and physical function to performance-based assessment of gait speed. Future studies are needed to confirm these associations and to explore mechanisms that underlie the conscientiousness mobility connection in aging adults. © 2012 The Author.

Ko S.-U.,Chonnam National University | Tolea M.I.,Clinical Research Branch | Hausdorff J.M.,Tel Aviv University | Hausdorff J.M.,Harvard University | Ferrucci L.,Clinical Research Branch
Journal of Biomechanics | Year: 2011

The effects of normal aging and orthopedic conditions on gait patterns during customary walking have been extensively investigated. Empirical evidence supports the notion that sex differences exist in the gait patterns of young adults but it is unclear as to whether sex differences exist in older adults. The aim of this study was to investigate sex-specific differences in gait among older adults. Study participants were 336 adults (50-96 years; 162 women) enrolled in the Baltimore Longitudinal Study of Aging (BLSA) who completed walking tasks at self-selected speed without assistance. After adjusting for significant covariates, women walked with higher cadence (p=0.01) and shorter stride length (p=0.006) compared to men, while gait speed was not significantly related to sex. Women also had less hip range of motion (ROM; p=0.004) and greater ankle ROM (p<0.001) in the sagittal-plane, and greater hip ROM (p=0.004) in the frontal-plane. Hip absorptive mechanical work expenditure (MWE) of the women was greater in the sagittal-plane (p<0.001) and lower in the frontal-plane (p<0.001), compared to men. In summary, women's gait is characterized by greater ankle ROM than men while men tend to have greater hip ROM than women. Characterizing unique gait patterns of women and men with aging may be beneficial for detecting the early stages of gait abnormalities that may lead to pathology. © 2011 Elsevier Ltd.

Ko S.-U.,Chonnam National University | Stenholm S.,Finnish National Institute for Health and Welfare | Metter E.J.,Clinical Research Branch | Ferrucci L.,Clinical Research Branch
Archives of Gerontology and Geriatrics | Year: 2012

The aim of the present study was to examine differences in gait characteristics across the adult lifespan and to test the hypothesis that such differences are attributable at least in part to the decline in muscle strength. The data presented here are from 190 participants of the Baltimore Longitudinal Study of Aging (BLSA) aged from 32 to 93. years. Based on two age thresholds that best capture the effect of age on walking speed, participants were divided into three age groups: middle-age (32-57. years; N= 27), old-age (58-78. years; N= 125), and oldest-age (79-93. years; N= 38). Participants were asked to walk at their preferred and maximum speeds while recorded with 3D gait analysis system. In addition, maximum isokinetic knee extensor strength was assessed. While walking at preferred speed, range of motion (ROM) and mechanical work expenditure (MWE) of the ankle were lower within middle-age (p< 0.001, p= 0.047, respectively), while hip ROM and MWE were lower (p= 0.006) and higher (p< 0.001), respectively within oldest-age with older age. Deterioration in ankle function during customary walking initiates already at middle-age. Differences in the maximum walking speed and ankle ROM between middle-age and old-age were explained by knee strength. © 2012 Elsevier Ireland Ltd.

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