Resistance Training Modulates the Humoral Inflammatory (but Not the DNA Methylation) Profile of Diabetic Older Adults Using Metformin.

BACKGROUND AND AIM: Inflammatory and methylation imbalances occur in patients with type 2 diabetes mellitus (T2DM). The aim of the present study was to analyze the effect of acute resistance exercise on the inflammatory profile and on DNA methylation of elderly patients with T2DM using metformin. METHODS: For this purpose, we enrolled 22 male and female older adults (68.2 ± 5.3 years), of whom 13 had controlled T2DM (D) under metformin use and 9 were nondiabetics (ND). All subjects underwent a neuromuscular circuit (8 exercises in 40 min, with each exercise performed in 3 sets of 40 s each and a 20-s interval between repetitions). RESULTS: The main results indicated a significant difference between groups for baseline interleukin (IL)-10, with a higher concentration in the D group compared to the ND group (p = 0.019). An increase in IL-6 concentration after intervention was observed in group D (p = 0.035). No effect was observed in total DNA methylation within or between groups. CONCLUSIONS: The resistance training protocol applied in this study modulates the IL-10 and IL-6 concentrations in elderly people with T2DM and under metformin use, possibly as a result of physiological adaptations, with no effect on nondiabetic elderly. No effects on absolute levels of DNA methylation were observed.

Serum Immune Mediators Independently Associate with Atherosclerosis in the Left (But Not Right) Carotid Territory of Older Individuals.

BACKGROUND AND AIM: Disturbance in the carotid arteries strongly predicts cerebrovascular events and correlates with a systemic inflammatory milieu. We investigated the relationship of a profile of 10 circulating inflammatory mediators with measures of carotid intima-media thickness (cIMT) in elderly subjects, taking traditional risk factors into account. METHODS: Clinical inspection for present and past chronic conditions and events, as well as biochemical and anthropometric measurements, was performed for patients in ambulatory setting. Scores of cIMT were obtained bilaterally in the distal common carotid artery wall. Serum concentrations of cytokines were assessed by bead-based, multiplexed flow cytometry immunoassays. RESULTS: Correlation analysis between log-transformed cytokines levels implicated the mediators interleukin-1ß (IL1ß), IL6, IL8, IL10, and tumor necrosis factor-α (TNFα) (P ≤ .005) with scores of the left cIMT. Stepwise multivariate regression showed that TNFα, IL1ß, and IL6 levels accounted for most of the variance in the cIMT scores. Comparison of cytokine levels across increasing tertiles of the left cIMT reproduced the positive association with TNFα and IL1ß levels. CONCLUSION: Five out of ten immune mediators independently correlated with cIMT of older subjects in a territory-sensitive manner. This possible contribution of immune mediators to an atherosclerotic process probably relates to the inflammaging process.

Lack of association between apolipoprotein E genotypes and cognitive performance in the non-demented elderly.

AIM: The ε4 alelle of the apolipoprotein E gene is known to be a key genetic risk factor for Alzheimer's disease and possibly for other neurological disorders. Some evidence in the literature indicates that the ε4 allele interferes with human cognition independently of chronological age and diagnosis of Alzheimer's disease. The present study investigated the correlation of allelic variants of apolipoprotein E with the cognitive performance of elderly individuals without apparent cognitive impairment. METHODS: This was a cross-sectional analysis that included 213 non-demented elderly individuals (age ≥60 years) from the Brazilian Federal District. The analysis assessed the subjects for cognitive domains including short- and long-term episodic memory, processing speed, and attention and executive functions. Sociodemographic and other clinical characteristics were gathered and analyzed as covariates. RESULTS: Being sufficiently powered, the present study did not identify differential performance across apolipoprotein E genotypes. There was no influence of age, gender, marital status, schooling, depressive symptoms or use of central nervous system depressants when the analyses were controlled for such factors. CONCLUSIONS: Our findings suggest that the ε4 allele does not contribute to detectable cognitive decline within the context of non-dementia.

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer.

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence.

Whole-Blood Levels of MicroRNA-9 Are Decreased in Patients With Late-Onset Alzheimer Disease.

Recent evidence suggests changes in circulating microRNA levels may be promising biomarkers for the clinical diagnosis of Alzheimer disease (AD). We hypothesized that whole-blood microRNAs may be useful to identify individuals with established AD. For this purpose, a sample of community-dwelling women (≥55 years old) carrying the ApoE ∊4 allele were clinically evaluated using the American Psychiatric Association/Diagnostic and Statistical Manual of Mental Disorders, Fourth edition and the Alzheimer Disease Assessment Scale-Cognitive Subscale criteria to diagnose probable AD, and the Clinical Dementia Rating scale to stage the dementia. A set of 25 mature microRNAs was rationally selected for evaluation based on experimental evidence of interaction with genes linked to the late-onset AD neuropathology. Whole-blood concentrations were determined by quantitative real-time polymerase chain reaction. Compared to patients without dementia, a median 3-fold decrease in miR-9 levels was found among patients with AD (P = .001). Our findings support blood-borne miR-9 as a candidate biomarker for probable AD, embodied by evidence from the literature of its implication in amyloidogenesis.

Fluid and imaging biomarkers for Alzheimer's disease: Where we stand and where to head to.

There is increasing evidence that a number of potentially informative biomarkers for Alzheimer disease (AD) can improve the accuracy of diagnosing this form of dementia, especially when used as a panel of diagnostic assays and interpreted in the context of neuroimaging and clinical data. Moreover, by combining the power of CSF biomarkers with neuroimaging techniques to visualize Aß deposits (or neurodegenerative lesions), it might be possible to better identify individuals at greatest risk for developing MCI and converting to AD. The objective of this article was to review recent progress in selected imaging and chemical biomarkers for prediction, early diagnosis and progression of AD. We present our view point of a scenario that places CSF and imaging markers on the verge of general utility based on accuracy levels that already match (or even surpass) current clinical precision.

Matrix Metalloproteinase-1 Gene Polymorphism Associated with Ultrasound-Assessed Carotid Thickness among Older Adults.

BACKGROUND AND AIM: Due to the high incidence of vascular diseases, it is necessary to identify new circulating or structural markers for predicting risk for chronic diseases. Some studies suggest that MMP1 gene polymorphisms are associated with the enzyme expression levels in situ (e.g., in atherosclerotic plaques). OBJECTIVES: Thus, the study of this polymorphism may help understanding the pathophysiology of coronary disease. METHODS: We performed cross-sectional clinical and laboratory evaluations (including measurement of intima-media thickness of carotid arteries) and genotyping of the MMP1 SNP rs495366 (A/G) in 366 elderly people. RESULTS: No significant differences between genotypes were noted for biochemical, metabolic, inflammatory, or clinical variables except for a significant difference in intima-media thickness for the left carotid artery and a trend toward significance for the right counterpart. CONCLUSION: Carriers of the allele associated with lower MMP1 expression (allele A) presented greater carotid thickness. We suggest that the phenomenon can be explained by impaired remodeling of the arterial wall (poor degradation of collagen fibers in this scenario), yielding carotid wall thickening and a greater intrinsic risk for cerebrovascular events.

Acute strength training promotes responses in whole blood circulating levels of miR-146a among older adults with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) consists of a set of metabolic and endocrine disorders which evolve into deficiency in insulin action and hyperglycemia. Physical exercise is considered the main intervention to prevent and control T2DM. Literature has suggested that circulating microRNAs (miRs) help to understand responses to physical activity among diabetic patients. Thus, the aim of this study was to analyze the acute effect of two interventions (strength and cardiovascular) on the total, whole blood circulating concentrations of miR-126, miR-146a and miR-155 in older adults with and without T2DM. A total of 23 male and female older adults (68.2±5.3 years) participated in the trial, 13 of whom presented with controlled T2DM and 10 were nondiabetics. They underwent both interventions separately, performed with intensity from 60% to 70% of reserve heart rate. Glucose and miRs levels were quantified and compared across groups with baseline titers as covariables. Diabetic patients showed more reduction in serum blood glucose than nondiabetics, with a great magnitude of reduction after the strength training intervention, which was paralleled by a positive change of the whole blood circulating levels of miR-146a, but not of the other miRs. Our report supports evidence that miR-146a levels in peripheral blood leukocytes are negatively associated with a state of insulin resistance, which is suggested as a novel marker to trace response to antidiabetic interventions.