Paraoxonase-1 55 LL Genotype Is Associated with No ST-Elevation Myocardial Infarction and with High Levels of Myoglobin

It is well known that serum paraoxonase (PON1) plays an important role in the protection of LDL from oxidation. PON1 55 polymorphism is currently investigated for its possible involvement in cardiovascular diseases. The objective of our study is to verify if PON1 55 polymorphism is associated with risk of acute coronary syndrome (ACS) and with biochemical myocardial ischemia markers, such as troponin I, creatine kinase (CK)-MB, myoglobin, and C-reactive protein. We analysed PON1 55 polymorphism in a total of 440 elderly patients who underwent an ACS episode: 98 patients affected by unstable angina (UA), 207 AMI (acute myocardial infarction) patients affected by STEMI (ST elevation), and 135 AMI patients affected by NSTEMI (no ST elevation). We found that individuals carrying PON1 55 LL genotype are significantly more represented among AMI patients affected by NSTEMI; moreover, the patients carrying LL genotype showed significantly higher levels of myoglobin in comparison to LM + MM carriers patients. Our study suggests that PON1 55 polymorphism could play a role in the pathogenesis of cardiac ischemic damage. In particular, the significant association between PON1 55 LL genotype and the occurrence of a NSTEMI may contribute to improve the stratification of the cardiovascular risk within a population

Red hot chili pepper and hemorrhoids: The explosion of a myth: Results of a prospective, randomized, placebo-controlled, crossover trial

PURPOSE: Spicy foods are appreciated by a large part of the world population but have been blamed for causing hemorrhoids or exacerbating their symptoms, although no epidemiologic studies have been performed supporting this hypothesis. In this double-blind, randomized, placebo-controlled, crossover trial, we have studied the effects of a single dose of red hot chili pepper on the hemorrhoidal symptoms. METHODS: Fifty patients with second-degree and third-degree symptomatic hemorrhoids were randomly assigned to take a capsule containing red hot chili powder or placebo during lunch, scoring five hemorrhoidal symptoms (bleeding, swelling, pain, itching, and burning) on a visual analog scale. After one week, crossover treatment was administered according to the same methodology. Other treatments and foods potentially related with anorectal symptoms were discontinued during the study periods. RESULTS: Patients assigned low scores to their hemorrhoidal symptoms before the study and the scores remained unchanged during the 48 hours after both placebo and chili pepper treatment, the latter showing no statistically significant effects. CONCLUSIONS: There is no scientific evidence that a spicy meal based on red hot chili pepper may worsen hemorrhoidal symptoms and, therefore, there is no reason to prevent these patients from occasionally enjoying a spicy dish if they so wish

Adiposity Predicts Cognitive Decline in Older Persons with Diabetes: A 2-Year Follow-Up

BACKGROUND: The mechanisms related to cognitive impairment in older persons with Type 2 diabetes (DM) remains unclear. We tested if adiposity parameters and body fat distribution could predict cognitive decline in older persons with DM vs. normal glucose tolerance (NGT). METHODOLOGY: 693 older persons with no dementia were enrolled: 253 with DM in good metabolic control; 440 with NGT (age range:65-85 years). Longitudinal study comparing DM and NGT individuals according to the association of baseline adiposity parameters (body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC) and total body fat mass) to cognitive change (Mini Mental State Examination (MMSE), a composite score of executive and attention functioning (CCS) over time. FINDINGS: At baseline, in DM participants, MMSE correlated with WHR (beta = -0.240; p = 0.043), WC (beta = -0.264; p = 0.041) while CCS correlated with WHR (beta = -0.238; p = 0.041), WC (beta = -0.326; p = 0.013) after adjusting for confounders. In NGT subjects, no significant correlations were found among any adiposity parameters and MMSE, while CCS was associated with WHR (beta = -0.194; p = 0.036) and WC (beta = -0.210; p = 0.024). Participants with DM in the 3(rd) tertile of total fat mass showed the greatest decline in cognitive performance compared to those in 1(st) tertile (tests for trend: MMSE(p = 0.007), CCS(p = 0.003)). Logistic regression models showed that 3(rd) vs. 1(st) tertile of total fat mass, WHR, and WC predicted an almost two-fold decline in cognitive function in DM subjects at 2(nd) yr (OR 1.68, 95%IC 1.08-3.52). CONCLUSIONS: Total fat mass and central adiposity predict an increased risk for cognitive decline in older person with DM

Paraoxonase Activity and Genotype Predispose to Successful Aging

The paraoxonase 1 codon 192 R allele has been previously reported to have a role in successful aging. The relationship between PON1 genotypes, enzymatic activity, and mass concentration was evaluated in a group of 229 participants from 22 to 104 years of age, focusing our attention on nonagenarian/centenarian participants. We found a genetic control for paraoxonase activity that is maintained throughout life, also in the nonagenarians/centenarians. This activity decreases significantly during aging and shows different mean values among R and M carriers, where R+ and M− carriers have the significant highest paraoxonase activity. Results from the multinomial regression logistic model show that paraoxonase activity as well as R+ and M− carriers contribute significantly to the explanation of the longevity phenotype. In conclusion, we show that genetic variability at the PON1 locus is related to paraoxonase activity throughout life, and suggest that both parameters affect survival at extreme advanced ag

N-Glycomic changes in serum proteins in type 2 diabetes mellitus correlate with complications and with metabolic syndrome parameters

Background: Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome. Methods: We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6 +/- 8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5 +/- 12.4 years). N-glycome was evaluated in serum glycoproteins. Results: We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, alpha(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6) A2F. In addition, NG1(6) A2F and NG1(3) A2F, identifying, respectively, monogalactosylated N-glycans with alpha(1,6)- and alpha(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme "unhealthy" phenotype (T2DM+ with MS). Conclusions: Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS

Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging.

none15noopenF Olivieri; L Spazzafumo; G Santini; R Lazzarini; MC Albertini; MR Rippo; R Galeazzi; AM Abbatecola; F Marcheselli; D Monti; R Ostan; E Cevenini; R Antonicelli; C Franceschi; AD Procopio.F., Olivieri; L., Spazzafumo; G., Santini; R., Lazzarini; Albertini, MARIA CRISTINA; Mr, Rippo; R., Galeazzi; Am, Abbatecola; F., Marcheselli; D., Monti; R., Ostan; E., Cevenini; R., Antonicelli; C., Franceschi; Ad, Procopi

A study protocol for identifying aging trajectories toward chronic neurodegenerative diseases by means of Marche regional administrative databases – TREND project

BackgroundPeople are living longer but an increasing number of older people experience chronicity and disability in the latest years of their life. The Marche region is one of the Italian regions where people live the longest lives; therefore, the number of people with age-related chronic diseases is expected to be at least similar, if not higher, compared to the rest of Italy. The identification of the aging trajectories is of huge interest in the arena of public health. Administrative healthcare databases represent valuable reservoirs for reconstructing the trajectories of aging. Here, we present the protocol for a study (TREND project) aimed to integrate existing administrative databases into a Marche regional dataset in order to estimate the prevalence and incidence rates of age-related neurodegenerative diseases (ND), with a specific focus on Parkinsonism and Dementia.MethodsThe TREND Project is a retrospective cross-sectional study. The source population includes permanent residents in the Marche region aged 40 years and older. A minimal dataset has been built up linking data on drug prescriptions, outpatient services, and diagnosis for hospital admission, from 2014 to 2021 in the Marche Region. Data on clinical outcomes (re-hospitalization, mortality, comorbidities), and therapeutic approaches (drugs and medicines) have been integrated with state-of-the-art statistical methods to define patients into different risk clusters and to analyze the aging trend by assessing the Comorbidity Index (CI) as a proxy for chronicity.DiscussionOur research contributes to the integration of existing administrative databases on ND to create a Marche regional ND database, support regional health policy, and better understand patients’ needs and their aging trajectories. This approach could be implemented also at the National level. Moreover, by linking different administrative data sources, this study sheds light on important issues related to ND, such as early-onset dementia; ethical aspects such as anticipated wills; problems of dementia in patients still in the job market, etc. The results of this study will contribute to the successful implementation of integrated care for patients affected by ND at regional or national levels

Mitochondrial DNA Backgrounds Might Modulate Diabetes Complications Rather than T2DM as a Whole

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure

Antifragility and antiinflammaging: Can they play a role for a healthy longevity?

: One of the most exciting challenges of the research on aging is to explain how the environmental factors interact with the genetic background to modulate the chances to reach the extreme limit of human life in healthy conditions. The complex epigenetic mechanisms can explain both the interaction between DNA and environmental factors, and the long-distance persistence of lifestyle effects, due to the so called "epigenetic memory". One of the most extensively investigated theories on aging focuses on the inflammatory responses, suggesting that the age-related progression of low-grade and therefore for long time subclinical, chronic, systemic, inflammatory process, named "inflammaging", could be the most relevant risk factor for the development and progression of the most common age-related diseases and ultimately of death. The results of many studies on long-lived people, especially on centenarians, suggested that healthy old people can cope with inflammaging upregulating the antiinflammaging responses. Overall, a genetic make-up coding for a strong antiinflammaging response and an age-related ability to remodel key metabolic pathways to cope with a plethora of antigens and stressors seem to be the best ways for reach the extreme limit of human lifespan in health status. In this scenario, we wondered if the antifragility concept, recently developed in the framework of business and risk analysis, could add some information to disentangle the heterogeneous nature of the aging process in human. The antifragility is the property of the complex systems to increase their performances because of high stress. Based on this theory we were wondering if some subjects could be able to modulate faster than others their epigenome to cope with a plethora of stressors during life, probably modulating the inflammatory and anti-inflammatory responses. In this framework, antifragility could share some common mechanisms with anti-inflammaging, modulating the ability to restrain the inflammatory responses, so that antifragility and antiinflammaging could be viewed as different pieces of the same puzzle, both impinging upon the chances to travel along the healthy aging trajectory