Importance and Meaning of TERRA Sequences for Aging Mechanisms

Abstract: Any theory suggesting an adaptive meaning for aging implicitly postulates the existence of specific mechanisms, genetically determined and modulated, causing progressive decline of an organism. According to the subtelomere–telomere theory, each telomere is covered by a hood formed in the first cell of an organism having a size preserved at each subsequent duplication. Telomere shortening, which is quantitatively different for each cell type according to the telomerase regulation, causes the hood to slide on the subtelomere repressing it by the telomeric position effect. At this point, the theory postulates existence of subtelomeric regulatory sequences, whose progressive transcriptional repression by the hood should cause cellular alterations that would be the likely determinant of aging manifestations. However, sequences with characteristics of these hypothetical sequences have already been described and documented. They are the [sub]TElomeric Repeat-containing RNA (TERRA) sequences. The repression of TERRA sequences causes progressively: (i) down- or up-regulation of many other regulatory sequences; (ii) increase in the probability of activation of cell senescence program (blockage of the ability to replicate and very significant alterations of the cellular functions). When cell senescence program has not been triggered and the repression is partial, there is a partial alteration of the cellular functions that is easily reversible by telomerase activation. Location of the extremely important sequences in chromosomal parts that are most vulnerable to repression by the telomeric hood is evolutionarily unjustifiable if aging is not considered adaptive: this location must be necessarily adaptive with the specific function of determining aging of the cell and consequently of the whole organism

Targeting oxidative stress for improving cardiovascular performance in the elderly

Oxidative stress is implicated in the pathophysiology of several cardiovascular diseases, as evidenced by correlation between oxidative stress markers and Heart Failure (HF) and by direct molecular evidence for an etiological role of reactive oxygen species (ROS). ROS play an important role in signalling processes, but their overproduction generates oxidative stress. Previous studies demonstrated that HF was associated with antioxidant deficit as well as increased oxidative stress. Furthermore, these changes correlated with the hemodynamic function, suggesting their role in the pathogenesis of cardiac dysfunction. An important mechanism involved in cellular cardiovascular response is represented by sirtuins. SIRT1 inhibition determines suppression of genes ac tivated by exposure to heat shock, on the contrary, SIRT1 activation enhances the heat shock response. Then the ability of SIRT1 to modulate stress resistance is multifaceted and not only linked to oxidative stress, but also to other stressful stimuli. Recently several studies have demonstrated the capability of physical activity to induce SIRT1 activity and, in turn, the ability of this enzyme to mediate the favourable antioxidant effects of the exercise training. Other agents able to induce SIRT1 activity have demonstrated some effects on cardiac function. Resveratrol supplementation has been shown to decrease cardiovascular risk factors, and the positive effect of resveratrol on training response and aerobic capacity in rats to be mediated via SIRT1. The future research should be addressed to better clarify the possible role of the antioxidants therapy in clinical studies, in particular defining a standardization of procedures, doses and duration of treatment

Exercise training in aging and diseases.

Sedentary lifestyle along with high blood pressure, abnormal values for blood lipids, smoking, and obesity are recognized risk factors for cardiovascular diseases and for many other chronic diseases, such as diabetes, osteoporosis, breast and colon cancer. Several studies conducted on large cohort of individuals have documented the protective effects of physical activity for both vascular and nonvascular syndromes. Exercise training is an integral part of cardiac rehabilitation, a complex therapeutic approach, effective both in young and elderly patients. Despite the number of evidences underling the benefits associated with physical fitness, the cardiac rehabilitation is still an underused medical resource. The molecular mechanism behind physical activity protective effect is presently unresolved, and further studies are also needed to establish the best protocol in terms of specificity, volume and duration of the training

Vehicle Navigation Service Based on Real-Time Traffic Information

GNSS-assisted vehicle navigation services are nowadays very common in most of the developed countries. However, most of those services are either delivered through proprietary technologies, or fall short in flexibility because of the limited capability to couple road information with real-time traffic information. This paper presents the motivations and a brief summary of a vehicle navigation service based on real-time traffic information, delivered through an open protocol that is currently under standardization in the Open Mobile Alliance forum

Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented

Whose Needs Does Service Serve? Complicating the Citizen Soldier Narrative

The growth of conscript militaries was integral to the creation of civil rights in European nation-states, which established militaries as a key site of claims-making. However, the United States military has diverged from these models, and most cases of inclusion or integration of social groups are not directly connected with claims-making. What has influenced the U.S. military’s responsiveness to pressures, both internal and external, and how has this changed over time? I employ a comparative historical approach to three cases—African-Americans, women, and non-heterosexuals—to unpack the U.S. military as a state institution and a site of claims-making. By incorporating elements unique to American institutions into existing models of militaries, I find that the U.S. military has become increasingly vulnerable to domestic political, international political, internal economic, and internal and external cultural pressures since the World War period. Despite its enormous economic and physical strength, the U.S. military is more responsive now than ever before to internal and external demands

Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Sex differences in cardiovascular disease (CVD) are often recognized from experimental and clinical studies examining the prevalence, manifestations, and response to therapies. Compared to age-matched men, women tend to have reduced CV risk and a better prognosis in the premenopausal period. However, with menopause, this risk increases exponentially, surpassing that of men. Although several mechanisms have been provided, including sex hormones, an emerging role in these sex differences has been suggested for β-adrenergic receptor (β-AR) signaling. Importantly, β-ARs are the most important G protein-coupled receptors (GPCRs), expressed in almost all the cell types of the CV system, and involved in physiological and pathophysiological processes. Consistent with their role, for decades, βARs have been considered the first targets for rational drug design to fight CVDs. Of note, β-ARs are seemingly associated with different CV outcomes in females compared with males. In addition, even if there is a critical inverse correlation between β-AR responsiveness and aging, it has been reported that gender is crucially involved in this age-related effect. This review will discuss how β-ARs impact the CV risk and response to anti-CVD therapies, also concerning sex and age. Further, we will explore how estrogens impact β-AR signaling in women

Hydropinotherapy with sulphurous mineral water as complementary treatment to improve glucose metabolism, oxidative status, and quality of life

Hydropinotherapy is a salus per aquam (Spa) treatment suitable as a complementary approach to treat several diseases, which strongly affect the quality of life (QoL). Hydropinotherapy with sulphurous mineral water exerts benefits thanks to components, such as hydrogen sulphide, which is considered mainly responsible for antioxidant and hypoglycaemic effects. Such properties, linked from each other, could favour an improvement in patients’ QoL. However, data on humans are scarce. This study aimed to investigate whether a cycle of sulphurous hydropinotherapy was able to modify plasma levels of glucose and reactive oxygen metabolites (ROMs) and improve QoL in patients suffering from several chronic disorders. A prospective, observational study involved patients with gastrointestinal diseases who received a prescription of a cycle of sulphurous hy-dropinotherapy (S-HT). Age-and sex-matched control group was enrolled (No S-HT). Glycaemia and plasma concentration of ROMs were measured in all subjects. The impact of spa treatment on the QoL was assessed using the Short Form 36 Health Status Survey questionnaire (SF-36). All parameters were measured at baseline and at the end of a 2-week treatment. Between the groups, no differences were found in glycaemia and ROMs at baseline. In the S-HT group, a reduction in glycaemia and ROMs, both in respect to baseline (p = 0.005 and p = 0.031, respectively) and to control group, as shown by the delta value calculated, as the difference between the values at 2 weeks and baseline (p = 0.0009 and p = 0.0001, respectively). In the S-HT, delta ROMs was the best predictor of delta glycaemia with a direct linear correlation (beta = 0.559, 95% CI 0.471 to 0.647, p < 0.0001). In the S-HT, the SF-36 total score was improved both when compared with baseline (p = 0.002) and with No S-HT (p = 0.001). Sulphurous hydropinotherapy induces a decrease in glycaemia and ROM levels, also ameliorating the patients’ QoL. Therefore, it could be considered a useful complementary therapeutic approach