Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement

Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and agerelated diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling agerelated low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing

Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement

Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and agerelated diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling agerelated low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing

Nutrigerontology: A key for achieving successful ageing and longevity

During the last two centuries the average lifespan has increased at a rate of approximately 3 months/year in both sexes, hence oldest old people are becoming the population with the fastest growth in Western World. Although the average life expectancy is increasing dramatically, the healthy lifespan is not going at the same pace. This underscores the importance of studies on the prevention of age-related diseases, in order to satisfactorily decrease the medical, economic and social problems associated to advancing age, related to an increased number of individuals not autonomous and affected by invalidating pathologies. In particular, data from experimental studies in model organisms have consistently shown that nutrient signalling pathways are involved in longevity, affecting the prevalence of age-related loss of function, including age-related diseases. Accordingly, nutrigerontology is defined as the scientific discipline that studies the impact of nutrients, foods, macronutrient ratios, and diets on lifespan, ageing process, and age-related diseases. To discuss the potential relevance of this new science in the attainment of successful ageing and longevity, three original studies performed in Sicily with local foods and two reviews have been assembled in this series. Data clearly demonstrate the positive effects of nutraceuticals, functional foods and Mediterranean Diet on several biological parameters. In fact, they could represent a prevention for many age-related diseases, and, although not a solution for this social plague, at least a remedy to alleviate it. Thus, the possibility to create a dietary pattern, based on the combined strategy of the use of both nutraceuticals and functional foods should permit to create a new therapeutic strategy, based not only on a specific bioactive molecule or on a specific food but on a integrated approach that, starting from the local dietary habits, can be led to a "nutrafunctional diet" applicable worldwide

Endothelial function and serum concentration of toxic metals in frequent consumers of fish

BACKGROUND:Endothelial dysfunction is involved in the pathogenesis of atherosclerosis. Consumption of fish is associated with reduced cardiovascular risk, but there is paucity of data concerning its effect on endothelial function. Furthermore, investigation of the effects of fish consumption on health must take into account the ingestion of contaminants, including transition metals and some metalloids, which may have unfavorable effects on health, including those on the cardiovascular system. We investigated the association between fish consumption, endothelial function (flow mediated dilation of the brachial artery), and serum concentration of some toxic metals in apparently healthy people. METHODS:Twenty-nine high fish consumers (at least 3 portions a week) were compared with 25 low fish consumers (less than 1 portion a week). All participants were free of diabetes, cardiovascular or other systemic diseases. Serum metal (antimonium, arsenic, mercury, lead, cobalt, copper, zinc, selenium, strontium) concentrations were measured in subgroups of 24 high fish consumers and 19 low fish consumers. RESULTS:Both groups exhibited similar habitual dietary patterns, age and anthropometric characteristics. The high fish consumers had higher flow mediated dilation (9.7 ± 1.8 vs. 7.3 ± 1.9%; P<0.001), but also higher serum concentrations of mercury (5.87 ± 2.69 vs. 1.65 ± 1.10 mcg/L; P<0.001) and arsenic (6.04 ± 3.25 vs. 2.30 ± 1.58 mcg/L; P<0.001). The fasting plasma glucose concentrations were significantly correlated with both mercury (r = 0.39; P = 0.01) and arsenic concentrations (r = 0.55; P<0.001). CONCLUSIONS:Habitual consumption of high amounts of fish is associated with better endothelial function despite higher serum concentrations of mercury and arsenic

Inflammation, genetic background and longevity

Ageing is an inexorable intrinsic process that affects all cells, tissues, organs and individuals. Due to a diminished homeostasis and increased organism frailty, ageing causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. Actually, it is characterized by a state of reduced ability to maintain health and general homeodynamics of the organism.Alarge part of the ageing phenotype is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status of ageing, ‘‘inflamm-ageing’’. It is strictly linked to immunosenescence, and on the whole they are the major contributory factors to the increased frequency of morbidity and mortality among elderly. Inflammageing is compatible with longevity; even if centenarians have an increased level of inflammatory mediators in comparison to old subjects and they are very frail, they also have high level of anti-inflammatory cytokines together with protective genotypes. Actually, data on case control studies performed in Italian centenarians suggest that a pro-inflammatory genotype is unfavourable to reach extreme longevity in good health and likely favours the onset of age-related diseases such as cardiovascular diseases and Alzheimer’s disease, the leading causes of mortality and disability in the elderly. However, many associations between gene variants and longevity have been found only in Italian population. This should not be unexpected, since ageing and longevity are complex traits resulting not only and not exclusively from genetics, but rather from the interactions between genetics, environment and chance

The signature of longevity in Sicily

Ageing is a natural and physiological condition that is the result of compromised stress response, homeostatic imbalance and increased risk of developing diseases. However, if aging with good health and functions (successful ageing) and aging with disease and disability (unsuccessful ageing) depends on a combination of “positive features”, including genetic, epigenetic and phenotypic characteristics in combination with favourable environment, economic status and social involvement. In our study, we summarize some key points for the identification of a longevity signature, with a particular focus on long-living Sicilian individuals and centenarians. Analysing three different Sicilian cohorts (young, people with no centenarian parents and long-living individuals (LLI) aged &gt;90) we found APOE e3e3 in our LLIs and no presence of e4. Regarding FOXO rs2802292 G-allele (G&gt;T) we did not observe an association with longevity, probably because of the small sample of centenarians studied. Regarding haematological and anthropometric results, it is still difficult to point specific longevity features and so far, we cannot specify a single one. On the other hand, we believe that the synergy among genetics and environment might create successful interaction to achieve and obtain effective longevity

Is the Secret in the Gut? SuperJump Activity Improves Bone Remodeling and Glucose Homeostasis by GLP-1 and GIP Peptides in Eumenorrheic Women

We showed that twenty weeks of SuperJump activity, an innovative workout training performed on an elastic minitrampoline, reduced bone resorption and increased bone formation in eumenorrheic women acting on the key points of the regulation of bone metabolism. The present study analyzed whether the gastrointestinal hormones are involved in the mechanism of action and if it has an impact on glucose homeostasis. The control group was composed of twelve women, similar to the exercise group that performed SuperJump activity for twenty weeks. The analysis was performed on blood samples and investigated GLP-1, GIP, GLP-2, PYY, ghrelin, glucose, insulin, insulin resistance, β-cell function, and insulin sensitivity. The results showed that the activity contributes to raising the GLP-1and GIP levels, and not on GLP-2, PYY, and ghrelin, which did not change. Moreover, SuperJump activity significantly reduced fasting insulin, glucose, insulin resistance, and increased insulin sensitivity but did not affect beta cell function. These data suggest that GLP-1, and GIP are involved in the mechanism of action that improves bone and glucose homeostasis following 20 weeks of SuperJump activity in eumenorrheic women

Predictive diagnostics and personalized medicine for the prevention of chronic degenerative diseases

Progressive increase of mean age and life expectancy in both industrialized and emerging societies parallels an increment of chronic degenerative diseases (CDD) such as cancer, cardiovascular, autoimmune or neurodegenerative diseases among the elderly. CDD are of complex diagnosis, difficult to treat and absorbing an increasing proportion in the health care budgets worldwide. However, recent development in modern medicine especially in genetics, proteomics, and informatics is leading to the discovery of biomarkers associated with different CDD that can be used as indicator of disease’s risk in healthy subjects. Therefore, predictive medicine is merging and medical doctors may for the first time anticipate the deleterious effect of CDD and use markers to identify persons with high risk of developing a given CDD before the clinical manifestation of the diseases. This innovative approach may offer substantial advantages, since the promise of personalized medicine is to preserve individual health in people with high risk by starting early treatment or prevention protocols. The pathway is now open, however the road to an effective personalized medicine is still long, several (diagnostic) predictive instruments for different CDD are under development, some ethical issues have to be solved. Operative proposals for the heath care systems are now needed to verify potential benefits of predictive medicine in the clinical practice. In fact, predictive diagnostics, personalized medicine and personalized therapy have the potential of changing classical approaches of modern medicine to CDD

Ammonium formate-Pd/C as a new reducing system for 1,2,4-oxadiazoles. Synthesis of guanidine derivatives and reductive rearrangement to quinazolin-4-ones with potential anti-diabetic activity

1,2,4-Oxadiazole is a heterocycle with wide reactivity and many useful applications. The reactive O-N bond is usually reduced using molecular hydrogen to obtain amidine derivatives. NH4 CO2 H-Pd/C is here demonstrated as a new system for the O-N reduction, allowing us to obtain differently substituted acylamidine, acylguanidine and diacylguanidine derivatives. The proposed system is also effective for the achievement of a reductive rearrangement of 5-(2′-aminophenyl)-1,2,4-oxadiazoles into 1-alkylquinazolin-4(1H)-ones. The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics

Post-acute COVID-19 neurological syndrome: A new medical challenge

In December 2019, in Wuhan (China), a highly pathogenic coronavirus, named SARS-CoV-2, dramatically emerged. This new virus, which causes severe pneumonia, is rapidly spreading around the world, hence it provoked the COVID-19 pandemic. This emergency launched by SARS-CoV-2 also had, and still has, devastating socio-economic aspects. Assessing the impact of COVID-19 on vulnerable groups of people is crucial for the adaptation of governments’ responses. Growing scientific evidence suggests that it is essential to keep the attention on people after acute SARS-CoV-2 infection; indeed, some clinical manifestations are frequently present even after recovery. There is consensus on the need to define which symptoms persist after the infection and which disabilities may arise after COVID-19. Recent reviews, case reports, and original contributions suggest that various organs may be affected, and neurological symptoms are present in about one third of patients with COVID-19. Neurological complications after severe COVID-19 infection might include delirium, brain inflammation, stroke, and nerve damage. In the recent pandemic, neurologists and neurobiologists have a chance to study key features of infection neurology. Furthermore, the psychological impact of the pandemic should not be underestimated, although there is currently no definition for this condition