Showing papers by "Giuseppe Paolisso published in 2013"

Mediterranean diet, telomere maintenance and health status among elderly.

Abstract: Leukocyte telomere length (LTL) and rate of telomere shortening are known biomarkers of aging while, numerous studies showed that Mediterranean diet (MD) may boost longevity. We studied association between telomere length, telomerase activity and different adherence to MD and its effects on healthy status. The study was conducted in 217 elderly subjects stratified according Mediterranean diet score (MDS) in low adherence (MDS≤3), medium adherence (MDS 4–5) and high adherence (MDS≥6) groups. LTL was measured by quantitative polymerase chain reaction and telomerase activity by a PCR-ELISA protocol. High adherence group showed longer LTL (p = 0.003) and higher telomerase activity (p = 0.013) compared to others. Linear regression analysis including age, gender, smoking habit and MDS showed that MDS was independently associated with LTL (p = 0.024) and telomerase activity levels (p = 0.006). Telomerase activity was independently associated with LTL (p = 0.007) and negatively modulated by inflammation and oxidative stress. Indeed, telomerase levels were associated with healthy status independently of multiple covariates (p = 0.048). These results support a novel role of MD in promoting health-span suggesting that telomere maintenance, rather than LTL variability is the major determinant of healthy status among elderly.

Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders

Abstract: Aims MicroRNAs (miRNAs) play an important role in the pathogenesis of structural alterations of the failing heart through their ability to regulate negatively the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodelling. We studied whether LV reverse remodelling after CRT was associated with changes of circulating miRNAs in patients with heart failure (HF) and dyssynchrony. Methods and results A prospective, non-randomized self-control trial was performed in 81 patients with HF eligible for CRT. At baseline, to select the HF miRNA profile, we evaluated the expression of 84 miRNAs (implicated in the pathogenesis of structural alterations of the failing heart) in three groups of patients: healthy subjects (healthy group, n = 15); patients with HF (HF group, n = 81); and patients without HF matched for age, sex, and concomitant disease with HF patients (control group, n = 60). At 12 months, the selected miRNA profile was evaluated in plasma from responder (n = 55) and non-responder HF patients (n = 26) to CRT. In the test cohort, the HF patients were characterized by lower expression of 48 miRNAs (all P < 0.04) as compared with healthy subjects. In the validation cohort, the HF patients were characterized by lower expression of 24 miRNAs (all P < 0.03) as compared with control patients. At 12 months, 55 patients (68%) were considered responders and 26 non-responders to CRT (32%). Responders showed an increase in expression of 19 miRNAs (all P < 0.03) compared with baseline expression, whereas in the non-responders we observed an increase of six miRNAs (all P < 0.05) compared with baseline expression. At follow-up, miRNAs were differentially expressed between responders and non-responders. The responders were characterized by higher expression of five miRNAs (miRNA-26b-5p, miRNA-145-5p, miRNA-92a-3p, miRNA-30e-5p, and miRNA-29a-3p; P < 0.01 for all) as compared with non-responders. Conclusions In responders, reverse remodelling is associated with favourable changes in miRNAs that regulate cardiac fibrosis, apoptosis, and hypertrophy.

Poor glycaemic control in type 2 diabetes patients reduces endothelial progenitor cell number by influencing SIRT1 signalling via platelet-activating factor receptor activation.

Abstract: Aims/hypothesis Downregulation of levels of endothelial progenitor cells (EPCs) during in-vitro short-term exposure to high glucose concentrations relates to reduced activity of silent information regulator 1 (SIRT1) and increased synthesis of platelet-activating factor (PAF). We investigated the possible relationship between PAF and SIRT1 pathways in EPCs during altered glucose homeostasis.

A new pleiotropic effect of statins in elderly: modulation of telomerase activity

Abstract: Recent evidence suggests a link between statins and telomere biology. Whether statin treatment may modulate telomerase activity and affect telomere erosion rate is unknown. We aimed at investigating the potential impact of statin therapy on peripheral blood mononuclear cells telomerase activity, its implication on LTL variability, and its association with telomere shortening rates along with aging. The cross-sectional study was conducted in 230 subjects (age range: 30-86 y) stratified according to statins treatment. LTL was measured by quantitative polymerase chain reaction and telomerase activity by a PCR-ELISA protocol. Subjects on statin treatment showed higher telomerase activity (P<0.0001) and longer LTL (P=0.028) levels compared to the nonstatin group. Statin therapy was associated with higher telomerase activity independently of multiple covariates, including age, gender, smoking habits, lipid, systemic inflammation, glucose, and blood pressure levels (P=0.019). Indeed, subjects on statin treatment showed significant lower telomere erosion along with aging. Every 1 y increment in age, LTL decreases by 0.058 Kb in no statin and 0.033 Kb in statin groups, respectively, as well as the major difference in telomere attrition between groups was found after the age of 65 yr (P<0.0001). In summary, statins, modulating telomerase activity, affect telomere erosion along with aging.

Association of Genetic Variation in Adaptor Protein APPL1/APPL2 Loci with Non-Alcoholic Fatty Liver Disease

Abstract: The importance of genetics and epigenetic changes in the pathogenesis of non alcoholic fatty liver disease (NAFLD) has been increasingly recognized. Adiponectin has a central role in regulating glucose and lipid metabolism and controlling inflammation in insulin-sensitive tissues and low adiponectin levels have been linked to NAFLD. APPL1 and APPL2 are adaptor proteins that interact with the intracellular region of adiponectin receptors and mediate adiponectin signaling and its effects on metabolism. The aim of our study was the evaluation of a potential association between variants at APPL1 and APPL2 loci and NAFLD occurrence. The impact on liver damage and hepatic steatosis severity has been also evaluated. To this aim allele frequency and genotype distribution of APPL1- rs3806622 and -rs4640525 and APPL2-rs 11112412 variants were evaluated in 223 subjects with clinical diagnosis of NAFLD and compared with 231 healthy subjects. The impact of APPL1 and APPL2 SNPs on liver damage and hepatic steatosis severity has been also evaluated. The minor-allele combination APPL1-C/APPL2-A was associated with an increased risk of NAFLD (OR = 2.50 95% CI 1.45–4.32; p<0.001) even after adjustment for age, sex, body mass index, insulin resistance (HOMA-IR), triglycerides and adiponectin levels. This allele combination carrier had higher plasma alanine aminotransferase levels (Diff = 15.08 [7.60–22.57] p = 0.001) and an increased frequency of severe steatosis compared to the reference allele combination (OR = 3.88; 95% CI 1.582–9.531; p<0.001). In conclusion, C-APPL1/A-APPL2 allele combination is associated with NAFLD occurrence, with a more severe hepatic steatosis grade and with a reduced adiponectin cytoprotective effect on liver.

Insulin-Like Growth Factor-1 Bioactivity Plays a Prosurvival Role in Older Participants

Abstract: The aim of this study was to address the intriguing issue of the role of the insulin-like growth factor (IGF)-1 system in longevity looking at the role of different components of IGF system. Vital status was ascertained in 1,197 men and women aged greater than or equal to 65 years from the InCHIANTI study. Hormonal levels were categorized into quartiles, and ratio of IGF-1 to IGF-binding protein (IGFBP)-1 was calculated. The relationship between hormones and mortality was tested by Cox proportional hazard models adjusted for age, sex, and confounders. During the 8-year follow-up period, 240 died and 957 survived. Lowest quartiles of IGF-1 and IGFBP-1 were considered as reference. Compared with the lowest quartiles, IGF-1 in upper quartiles was a negative predictor of mortality independent of age and sex ( p = .01) but not independent of IGFBP-1 and other confounders. IGFBP-1 in second–third quartiles was negatively associated and that in the fourth quartiles was positively associated with risk of death. IGF-1/IGFBP-1 ratio in the lowest quartiles was a strong positive predictor of mortality, in age- and sex-adjusted model (p = .005), and independent of additional confound

Polyphenols, Oxidative Stress, and Vascular Damage in Diabetes

Abstract: Oxidative stress induced by hyperglycemia is a key factor in the development and progression of diabetes and its vascular complications. Dietary polyphenols have received enormous attention because their consumption has been associated with lower rates of diabetes and cardiovascular diseases. These compounds are of plant origin, and are abundant in fruit, vegetables, chocolate, and nuts, as well as in beverages such as tea, coffee, wine, and soy milk. They can be divided into at least ten separate classes, four of which are important in the human diet: phenolic acids, flavonoids, stilbenes, and lignans. A number of in vitro and in vivo studies support the effect of polyphenols on glucose metabolism, diabetes risk, and diabetic impairments in the nitric oxide-mediated endothelial progenitor cell mobilization and homing. This chapter intends to review the current knowledge on polyphenols, oxidative stress, and vascular damage in diabetes, focusing on the most important and recent advances and challenges for future research.

Perspective: Protein and Exercise for Frailty and Sarcopenia: Still Learning

Abstract: Likewise, no definite evidenceis available regarding the differential effects of animal-derived andplant-based proteins on muscle health in old age. This issue is ofparticular interest considering that proteins with different aminoacidcompositionshowspecificabsorptionrates.Hencetheconceptof “fast” (eg, whey protein) versus “slow” protein (eg, casein andmeat proteins) needs to be taken into consideration for thedevelopment of nutritional recommendations, as well as for theprescription of specific supplements.

Malleability of Short Telomeres by Telomerase Activators: A Mini-review

Abstract: Most human cells lack sufficient telomerase to maintain telomeres; hence they shorten with each cellular division leading to organismal aging and disabling age-related diseases susceptibility. Genetic studies in mice demonstrated that short telomeres rather than average telomere length are associated with most age-related diseases and that rescue of short telomeres by telomerase is sufficient to restore cell and tissues viability. Novel findings in telomerase activation suggested its role as a new therapeutic strategy to prevent or at least retard cellular senescence and organismal decline, potentially impacting on human health.

“The Older, the Wiser” in Prostate Cancer Treatment Choices?

Abstract: In this issue, Daskivich and colleagues investigated the effect of age, tumor risk, and comorbidity on survival in a large population-based cohort of men older than 60 years with prostate cancer. T...

Response to Comment on: Rizzo et al. Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076–2082

Abstract: DeVries (1) was surprised that vildagliptin and sitagliptin groups reported different mean amplitude of glycemic excursions (MAGE) reduction because they have similar fasting and postprandial glucose levels and suggested reporting other measures of glucose variability to better understand these results. Indeed, a previous study evaluating the role of glycemic variability in type 2 diabetic patients has demonstrated that patients with similar mean glucose and postprandial glucose have a markedly different daily glucose profile with differences both in number and duration of excursions (2). The difference in MAGE reduction found in the two study groups …

Unbalance Glycometabolic in Elderly Woman None Diabetic COPD Patients

Abstract: Background : It has been estimated that by 2020, the Chronic Obstructive Pulmonary Disease (COPD) will be the third place among the most important causes of death in all over the world. Studies focusing on risk factors that influence the admission or readmission to the hospital are limited. The administration of medications can contribute to unplanned readmission. Moreover, in the course of COPD, treatment with cortisone determines a high risk of worsening of glucose control. The guidelines on the management of COPD do not address this issue in detail, although the number of COPD patients with diabetes mellitus is considerable and significant. Clinical studies designed specifically on this population are needed in order to identify effective and safe therapeutic pathways. Methods : We conducted an observational, descriptive study in a health area of the Molise Region that included 300 elderly subjects aged ? 65 and followed from June 2012 to June 2013. Results and Conclusions: Our preliminary study revealed that the prevalence of unbalance glycometabolic (as indicated by HbA1c > 7%) in COPD patients was > 50%. In particular, this difference was more frequent in COPD woman patients and it warrants further investigation. doi: http://dx.doi.org/10.4021/jem194e