Background-We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption.

Objective To better understand the contribution of age to the development of osteoarthritis (OA). Methods Surgical destabilization of the medial meniscus (DMM) was used to model OA in 12 week-old and 12 month-old male C57/BL6 mice. OA severity was evaluated histologically. RNA used for microarrays and real-time PCR was isolated from joint tissue collected from the medial side of the joint, including cartilage, meniscus, subchondral bone, and joint capsule with synovium. Computational analysis was used to identify patterns of gene expression and immunohistochemistry to evaluate tissue distribution of selected proteins. Results OA was more severe in older mice than young. Only 55 genes showed a similar expression with DMM-induced OA in the two age groups while 493 genes showed differential expression, the majority having increased expression in older mice. Functional categories for similarly expressed genes included extracellular matrix and cell adhesion related genes; differentially expressed genes included muscle structure and development and immunoglobulin domain genes. Comparison of expression in the sham control joints revealed an age-related decrease in matrix gene expression and an increase in immune and defense response genes. IL-33 was present in multiple joint tissue cells while CCL21 was more localized to chondrocytes and meniscal cells. Periostin was found in the extracellular matrix of cartilage and meniscus. Conclusion Age affects both the basal pattern of gene expression in joint tissues and the response to surgically-induced OA. Examining tissue from the joint beyond only cartilage revealed novel genes and proteins that would be important to consider in OA.

Background Hypertension (HTN) is a risk factor for dementia and animal studies suggest that centrally active (cross the blood brain barrier) angiotensin converting enzyme (ACE) inhibitors may protect against dementia beyond HTN control. Methods Participants in the Cardiovascular Health Study cognition substudy (mean age 75 yrs) with treated HTN and no diagnosis of heart failure (n= 1054) were followed for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared to other antihypertensive agents, was associated with lower risk of incident dementia, cognitive decline (by the modified mini mental state exam, 3MSE), or incident disability in instrumental activities of daily living (IADL). Results Among 414 participants exposed to ACE inhibitors and 640 not, there were 158 cases of incident dementia. Compared to other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (HR 1.01, 95% CI 0.88–1.15), difference in 3MSE scores (−0.32 points/yr, p=0.15), or odds of IADL disability (OR (95% CI) 1.06 (0.99–1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (p= 0.01) and non-centrally active ACE inhibitors were associated with greater risk of incident dementia (adjusted HR 1.20 (1.00–1.43) per year of exposure) and greater odds of IADL disability (adjusted OR 1.16 (1.03–1.30) per year of exposure) compared to other anti-HTN drugs. Conclusions While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within class differences in regards to these outcomes. These results should be confirmed with an RCT of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.