Environmental stress,ageing and glial cell senescence: a novel mechanistic link to Parkinson's disease?

Exposure to environmental toxins is associated with a variety of age‐related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age‐related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti‐cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence‐associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age‐related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder.     

Does ageing affect zinc homeostasis and dietary requirements?

Dietary intakes of zinc are lower in the elderly because of reduced energy requirements, and it is not clear whether ageing impacts on adaptive homeostatic mechanisms, namely absorptive efficiency and endogenous losses in the GI tract. Physiological requirements for zinc are unlikely to change significantly, but there are several attributes of ageing that may affect aspects of zinc metabolism (e.g. changes in gut structure and function, disease states, chronic inflammation, epigenetic changes in genes that express zinc-related proteins and drug regimens) that are worthy of further investigation. There is, as yet, no information on the effects of ageing on zinc transporters, and there are no sensitive and specific measures of zinc status, therefore dietary recommendations for zinc have been derived from factorial calculations using information on zinc absorption and loss, and estimates of dietary bioavailability.     

Does metabolic syndrome predict significant angiographic coronary artery disease?

IntroductionMetabolic syndrome (MS) is an independent predictor of acute cardiovascular events. However, few studies have addressed the relationship between MS and stable angiographic coronary artery disease (CAD), which has a different pathophysiological mechanism. We aimed to study the independent predictors for significant CAD, and to analyze the impact of MS (by the AHA/NHLBI definition) on CAD.MethodsWe prospectively included 300 patients, mean age 64 ± 9 years, 59% male, admitted for elective coronary angiography (suspected ischemic heart disease), excluding patients with known cardiac disease. All patients underwent assessment of demographic, anthropometric, and laboratory data and risk factors, and subsequently underwent coronary angiography.ResultsIn the study population, 23.0% were diabetic, 40.5% had MS (and no diabetes) and 36.7% had neither diagnosis. Significant CAD was present in 51.3% of patients. CAD patients were older and more frequently male and diabetic, with increased triglycerides and glucose and lower HDL cholesterol. Abdominal obesity was also less prevalent. MS was not associated with the presence of CAD (OR 0.94, 95% CI 0.59–1.48, p=0.778). Of the MS components, the most important predictors of CAD were increased glucose and triglycerides. Abdominal obesity was associated with a lower risk of CAD. In a multivariate logistic regression model for CAD, independent predictors of CAD were age, male gender, glucose and triglycerides. Body mass index had a protective effect.ConclusionsAlthough MS is associated with cardiovascular events, the same was not found for stable angiographically proven CAD. Age, gender, diabetes and triglycerides are the most influential factors for CAD, with abdominal obesity as a protective factor.     

Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease?

Much controversy has surrounded both the pathological basis and the clinical utility of the metabolic syndrome. Key questions still revolve around the definition of this syndrome, its utility as a predictor of cardiovascular risk, and the treatment implications of diagnosis. The metabolic syndrome is associated with increased cardiovascular risk. However, the metabolic syndrome clearly underperforms compared with other, established prediction equations, such as the Framingham Risk Score and SCORE (Systemic COronary Risk Evaluation). Differences arise because the components are highly correlated (whereas other tools specifically include independent predictors) and because diagnosis is based on dichotomized variables. These facts, together with uncertain pathophysiology, mean that the metabolic syndrome in its current manifestation has limited utility for the diagnosis and treatment of cardiovascular disease. The syndrome has, however, served and continues to serve a useful purpose in raising awareness of the metabolic consequences of obesity, and as a spur for research into metabolic risk factor interactions.     

Does ageing originate in utero?

Ageing still remains a conundrum on the cellular and molecular level, while environmental factors and interactions further increase the complexity of the ageing process. On the other hand is cancer, for which 20 years ago, it was proposed by Trichopoulos that it might have intrauterine origin. We herein discuss the idea that parameters such as the influence of insulin-like growth factor (IGF) signalling, of hormones and of the number of stem cells, as well as the effect of foetal and early life nutrition on ageing may also commence in utero and we provide epidemiological and biological data to advocate for this hypothesis. Finally, we analyse the public health implication of this hypothesis based on the World Health Organization (WHO) report that the burden of diseases, including ageing, may be due to impaired foetal development.     

Pre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy?

Complications of pregnancy, particularly pre-eclampsia (PET) and intra-uterine growth restriction (IUGR) have been associated with future maternal cardiovascular disease (CVD). Pre-eclampsia, characterised by insulin resistance, widespread endothelial damage and dysfunction, coagulation defects and increased systemic inflammatory response, shares many risk factors with CVD. This review describes the pathology of PET and the maternal metabolic response and discusses the possible underlying mechanisms common to CVD and PET. The contributions of pre-existing risk factors and of the exaggerated atherogenic-like response seen in PET persisting post-partum to future CVD are considered. The potential for interventions based on early assessment of cardiovascular risk is addressed. We conclude that despite the low immediate cardiovascular risk in a population of young women, a pregnancy with multiple complications including PET, premature delivery and IUGR, carries a seven-fold additive risk of future disease. These women may be an appropriate cohort for CVD risk screening and for possible intervention.     

Does bariatric surgery cure the metabolic syndrome?

Metabolic syndrome (MS) is a risk condition for the development of systemic atherosclerotic disease. Morbid obesity is a state of insulin resistance (IR) associated with visceral fat accumulation, which is involved in the development of MS. In severe obesity, conservative therapies promote an improvement of MS, but weight regain is frequent, whereas bariatric surgery promotes a more significant and sustained weight loss. Bariatric surgery is recommended for patients with unsatisfactory response to clinical treatment and with IMC > 40 kg/m(2) or > 35 in case of co-morbidities. In those cases, surgical risk must be acceptable and patients submitted to surgery must be informed about complications and postoperative care. Prevention, improvement and reversion of diabetes (DM2) (70 to 90% of cases) are seen in several bariatric surgery modalities. Disabsorptive are more efficient than restrictive procedures in terms of weight reduction and insulin sensitivity improvement, but chronic complications, such as malnutrition, are also more frequent. Vertical gastroplasty with jejunoileal derivation is a mixed surgery in which the restrictive component predominates. In this modality, reversion of DM2 is due to an increase in insulin sensitivity associated with improved beta cell function. Reversion of MS and its manifestations after bariatric surgery are associated with reduction of cardiovascular mortality and, thus, in severe obesity cases, MS can be considered a surgical condition.     

Are functional and demographic senescence genetically independent?

Biogerontology has traditionally focused on demographic senescence by searching for environmental manipulations and genes that extend life span. Relatively little is known about age-specific changes in functional traits and how demographic and functional senescence are genetically (co)regulated. To determine whether functional and demographic senescence have a similar genetic basis, we measured genotypic variation in the age-related change in cold-stress resilience and age-specific mortality using ten inbred lines of Drosophila melanogaster. Cold-stress resilience was measured as the average time for a population of flies to recover from a chill coma after being placed on melting ice for 6 h. We found genotypic variation in both sexes for chill-coma resilience, for the rate at which it declines with age, for longevity, for the initial mortality rate, and for the rate at which mortality increases with age. However, there was no genotypic correlation between any of these functional and demographic parameters. These results suggest that deterioration of at least some functional traits might be genetically independent of mortality patterns. Models for the genetic basis of senescence may do well to distinguish between quality and quantity of life in terms of their genetic architectures, and the way selection acts upon these two age-related factors.