86 research outputs found

    Trajectories in muscular strength and physical function among men with and without prostate cancer in the health aging and body composition study

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    Objectives To examine and compare changes in strength and physical function from pre- to post-diagnosis among men with prostate cancer (PC, [cases]) and matched non-cancer controls identified from the Health, Aging and Body Composition (Health ABC) study. Materials and methods We conducted a longitudinal analysis of 2 strength and 3 physical function-based measures among both cases and controls, identified from a large cohort of community living older adults enrolled in the Health ABC study. We plotted trajectories for each measure and compared cases vs. controls from the point of diagnosis onwards using mixed-effects regression models. For cases only, we examined predictors of poor strength or physical function. Results We identified 117 PC cases and 453 matched non-cancer controls (50% African Americans). At baseline, there were no differences between cases and controls in demographic factors, comorbidities or self-reported physical function; however, cases had slightly better grip strength (44.6 kg vs. 41.0 kg, p\u3c0.01), quadriceps strength (360.5 Nm vs. 338.7 Nm, p = 0.02) and Health ABC physical performance battery scores (2.4 vs. 2.3, p = 0.01). All men experienced similar declines in strength and physical function over an equivalent amount of time. The loss of quad strength was most notable, with losses of nearly two-thirds of baseline strength over approximately 7 years of follow up. Conclusions Among both cases and controls, strength and physical function decline with increasing age. The largest declines were seen in lower body strength. Regular assessments should guide lifestyle interventions that can offset age- and treatment-related declines among men with PC

    Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

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    Background: Middle age obesity is recognized as a risk factor for Alzheimer’s disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings: To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance: Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-a and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokin

    Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

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    The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention
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