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Abstract: Adult neurogenesis deficiency has been proposed to be a common hallmark in different age-related neurodegenerative diseases. The administration of flavonoids is currently reported as a potentially beneficial strategy for preventing brain aging alterations, including adult neurogenesis decline. Flavonoids are a class of plant-derived dietary polyphenols that have drawn attention for their neuroprotective and pro-cognitive effects. Although they undergo extensive metabolism and localize in the brain at low concentrations, flavonoids are now believed to improve cerebral vasculature and interact with signal transduction cascades involved in the regulation of adult neurogenesis. Further-more, many dietary flavonoids have been shown to reduce oxidative stress and neuroinflammation, improving the neuronal microenvironment where adult neurogenesis occurs. The overall goal of this review is to summarize the evidence supporting the role of flavonoids in modulating adult neurogene-sis as well as to highlight how these dietary agents may be promising candidates in restoring healthy brain function during physiological and pathological aging.

One of the characteristics of the SARS-CoV-2 infection in Italy is the significant regional difference in terms of lethality and mortality. These geographical variances were clear in the first wave and confirmed in the second one as well. The study aimed to analyze the correlation between regional differences in COVID-19 mortality and different regional care models, by retrospectively analyzing the association between the Italian COVID-19 deaths and the number of hospital beds, long-term care facilities, general practitioners (GPs), and the health expenditure per capita. The period considered was from 1 March 2020 to 1 March 2021. The number of hospital beds (p < 0.0001) and the number of GPs (p = 0.0094) significantly predicted the COVID-19 death rate. The Italian regions with a higher number of hospital beds and a lower number of GPs showed a higher number of deaths. Multivariate analyses confirmed the results. The Italian regions with a higher amount of centralized healthcare, as represented by the number of hospital beds, experienced a higher number of deaths, while the regions with greater community support, as exemplified by the number of the GPs, faced higher survival. These results suggest the need for a change in the current healthcare system organization.

Background: Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease risk. We describe a simple, sensitive and non-invasive method for estimating the n-3 index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in dried blood spots (DBSs). Experimental: After obtaining DBSs on a spot card, PUFAs were transesterified (direct, acidic transesterification) and subsequently extracted with n-hexane. Gas chromatography with flame ionization detection (GC-FID) was used to analyze the extracted PUFAs, and then n-3 index and AA/EPA ratio were calculated. Method validation showed satisfactory precision and linearity. Conclusion: This analysis is simple and reliable to estimate PUFA status, and it was successfully applied to samples from 20 subjects, demonstrating its applicability.

Cardiovascular disease (CVD) remains the leading cause of death today. Many of the biochemical alterations associated with the pathophysiology of CVD can be modified by adequate intakes of bioactive nutrients through a correct diet or supplementation. Recently, there has been growing public and clinical interest in cocoa polyphenols (CPs) and omega-3 (ω-3) fatty acids. A plethora of nutritional intervention trials and experimental studies demonstrates that consumption of these bioactive food compounds is beneficial to promote cardiovascular health. The purpose of this review is to summarize the major cardioprotective effects of CPs and ω-3 fatty acids, providing a scientific rationale for incorporating the combination of these molecules as a nutritional intervention in the prevention of CVD. Although several studies have shown the individual cardioprotective nature of these compounds, a combination treatment with CPs and ω-3 fatty acids may be a promising approach to enhance the preventive value of these molecules and reduce cardiovascular risk factors associated with aging. Therefore, this article also reviews some of the key studies on the interaction between CPs and the metabolism of ω-3 fatty acids.

The aim of this study was to examine the association between biomarkers of polyunsaturated fatty acids (PUFA), such as omega-3 (ω-3) index and arachidonic acid (AA; 20:4 ω-6)/eicosapentaenoic acid (EPA; 20:5ω-3) ratio (AA/EPA), and the prevalence of running-related injuries (RRI) in a cohort of recreational runners. We performed a retrospective, observational study of 275 non-elite runners (mean age: 41.20 ± 12.47 years) who were not supplemented with ω-3 fatty acids. The training characteristics and RRI were recorded over a period of 12 months through a self-reported questionnaire. Using whole blood samples collected by finger prick, PUFA were quantified by gas chromatography and ω-3 index and AA/EPA ratio measured. A total of 191 RRI cases were reported, with an injury prevalence rate of 50.9% in the overall population. The injured runners ran a significantly greater weekly distance than uninjured subjects (53.54 ± 25.27 km/week; p = 0.007). In a multivariate regression analysis, the lowest number of RRI was associated with higher values of ω-3 index (β = - 0.237; 95% CI - 0.308 to - 0.164; R2 = 0.172; p

The use of Silybum marianum L. for therapeutic purposes has been known since ancient times. Its phytocomplex reduces transaminases and other biohumoral indices in the course of liver disease and also in hepato-renal syndrome. In particular, the flavonolignan component has shown properties that would partially explain the ability of the phytocomplex to induce a certain regeneration of liver cells, stimulate the cellular elimination of toxins and reduce the inflammatory component, present in fatty, alcoholic and hormonal therapies with steroids. S. marianum is also successfully used in the treatment of patients with symptomatic chronic hepatitis, with complete disappearance of clinical symptoms, such as asthenia, loss of appetite, severe meteorism, dyspepsia, and with normalization of transaminases. The same results can be obtained in patients undergoing heavy chemotherapy cycles. Modern herbal medicine uses it in decoction or infusion, however with some caution in patients suffering from hypertension, due to the presence of tyramine. In addition, the extracts of the roots have antioxidant, diuretic and febrifugal properties and those of the leaves have aperitif properties. It is therefore interesting to provide a picture of the different non-flavonolignanic components (terpenes, steroids and essential oils) of the plant and their properties, which have perhaps been wrongly neglected over the past few years.

Mediterranean diet (MedDiet) is rich in fruits and vegetables associated with longevity and a reduced risk of several age-related diseases. It is demonstrated that phytochemicals in these plant products enhance the positive effects of MedDiet by acting on the inflammatory state and reducing oxidative stress. Evidence support that these natural compounds act as hormetins, triggering one or more adaptive stress-response pathways at low doses. Activated stress-response pathways increase the expression of cytoprotective proteins and multiple genes that act as lifespan regulators, essential for the ageing process. In these ways, the hormetic response by phytochemicals such as resveratrol, ferulic acid, and several others in MedDiet might enhance cells' ability to cope with more severe challenges, resist diseases, and promote longevity. This review discusses the role of MedDiet phytochemicals in healthy ageing and the prevention of age-related diseases.

Data supporting the use of Tocilizumab (TCZ) in COVID-19 are contrasting and inconclusive. This meta-analysis aimed to assess TCZ effectiveness in reducing the mortality rate in COVID-19 patients. PubMed, Scopus, Embase, Cochrane, WILEY, and ClinicalTrials.gov were searched to evaluate observational studies and RCTs. The outcome was the mortality rate. Forty observational studies and seven RCTs, involving 9640 and 5556 subjects treated with Standard Therapy (ST) + TCZ or ST alone, respectively, were included. In patients treated with ST+TCZ, a higher survival (Log odds ratio = −0.41, 95% CI: −0.68 −0.14, p &lt, 0.001) was found. Subgroups analyses were performed to better identify the possible interference of some parameters in modifying the efficacy of TCZ therapy on COVID-19 mortality. Separating observational from RCTs, no statistically significant (p = 0.70) TCZ-related reduction of mortality regarding RCTs was found, while a significant reduction (Log odds ratio = −0.52, 95% CI: −0.82 −0.22, p &lt, 0.001) was achieved regarding the observational studies. Stratifying for the use of Invasive Mechanic Ventilation (IMV), a higher survival was found in patients treated with TCZ in the No-IMV and IMV groups (both p &lt, 0.001), but not in the No-IMV/IMV group. Meta-regression analyses were also performed. The meta-analysis of observational studies reveals that TCZ is associated with reducing the mortality rate in both severe and critically ill patients. Although the largest RCT, RECOVERY, is in line with this result, the meta-analysis of RCTs failed to found any difference between ST + TCZ and ST. It is crucial to personalize the therapy considering the patients’ characteristics.

Background: Emerging studies show that certain plant compounds may reduce the severity of most prevalent ocular abnormalities. The aim of this systematic review and meta-analysis was to assess the effect of dietary flavonoids on major eye disorders.Methods: Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Cochrane Library databases for all articles published up to April 2021. The literature search yielded 1,134 articles, and a total of 16 studies were included in the systematic review. A meta-analysis of 11 intervention trials involving a total of 724 participants was performed.Results: Using a random-effects model, the pooled results revealed an overall significant effect of flavonoids on common ophthalmic disorders (standard mean difference = −0.39; 95% CI: −0.56, −0.21, p < 0.01). Of the subclasses of flavonoids, flavan-3-ols (standard mean difference = −0.62; 95% CI: −1.03, −0.22, p < 0.01), and anthocyanins (standard mean difference = −0.42; 95% CI: −0.63, −0.21, p < 0.01) were the only effective intervention for improving the outcomes of ocular conditions. For several of the other flavonoid subclasses, evidence on efficacy was insufficient.Conclusion: Our findings indicate that flavonoids may improve the clinical manifestations associated with ocular disorders. However, further well-constructed clinical trials are required to confirm these results and examine the effect of flavonoids on eye disorders other than those identified in this review.Systematic Review Registration: PROSPERO, identifier CRD42021247332.

Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary supplements. Our aim was to conduct a systematic review to evaluate the effects of dietary flavonoids on the symptoms of depression. A total of 46 studies met the eligibility criteria. Of these, 36 were intervention trials and 10 were observational studies. A meta-analysis of 36 clinical trials involving a total of 2788 participants was performed. The results showed a statistically significant effect of flavonoids on depressive symptoms (mean difference = −1.65; 95% C.I., −2.54, −0.77; p < 0.01). Five of the 10 observational studies included in the systematic review reported significant results, suggesting that a higher flavonoid intake may improve symptoms of depression. Further studies are urgently required to elucidate whether causal and mechanistic links exist, along with substantiation of functional brain changes associated with flavonoid consumption.

The n-3 and n-6 polyunsaturated fatty acids (PUFA) are among the most studied nutrients in human metabolism. In the past few decades, prospective studies and controlled trials have supported the view that the effects of these essential fatty acids are clinically relevant. PUFA profiles in different blood compartments are reflections of both diet and metabolism, and their levels may be related to disease risk. Despite widespread interest, there is no consensus regarding which biomarkers best reflect PUFA status in the body. The measurement of PUFA levels is not straight-forward, and a wide variety of indices have been used in clinical studies, producing conflicting results. A major source of heterogeneity among studies is associated with research design, sampling, and laboratory analyses. To date, the n-3 index, n-6/n-3 ratio, and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio are the most promising biomarkers associated with PUFA metabolism. Although hotly debated, these indices may be considered at least markers, if not risk factors, for several diseases, especially cardiovascular events and brain disorders. Here, we summarize the most updated evidence of n-3 and n-6 PUFA effects on human health, reviewing current controversies on the aforementioned indices and whether they can be considered valuable predictors of clinical outcomes.

Dietary phytochemicals are considered an innovative strategy that helps to reduce cardiovascular risk factors. Some phytochemicals have been shown to play a beneficial role in lipid metabolism, to improve endothelial function and to modify oxidative stress pathways in experimental and clinical models of cardiovascular impairment. Importantly, investigation on phytochemical effect on cardiac remodeling appears to be promising. Nowadays, drug therapy and implantation of devices have demonstrated to ameliorate survival. Of interest, sex-gender seems to influence the response to HF canonical therapies. In fact, starting by the evidence of the feminization of world population and the scarce efficacy and safety of the traditional drugs in women, the search of alternative therapeutic tools has become mandatory. The aim of this review is to summarize the possible role of dietary phytochemicals in HF therapy and the evidence of a different sex-gender-oriented response.

Background: Tissue availability of polyunsaturated fatty acids (PUFA) depends on several factors, including dietary intake, physical exercise, genetic variation, and metabolic turnover. However, there is limited evidence whether running training activity per se may influence indices associated with PUFA metabolism such as Omega-3 (ω-3) index and arachidonic acid (AA; 20:4ω-6)/eicosapentaenoic acid (EPA; 20:5ω-3) ratio. Objective: To examine the association between kilometers (Km) run per week and changes in ω-3 index and AA/EPA ratio. Methods: We conducted a retrospective, observational, cohort study of 257 non-elite runners (mean age: 40.85 ± 12.17 years) who consumed no fatty acid supplements and provided a blood sample for analysis. The whole blood samples were collected by finger sticks, stored on absorbent filter paper, and then PUFA were quantified by gas chromatography (GC) and ω-3 index and AA/EPA ratio measured. Results: In a multivariate linear regression model, a gradual decrease of the ω-3 index was observed with higher weekly running distance (β = −0.033; 95% CI −0.039 to −0.026; R2 = 0.447; p < 0.0001). We also found a progressive increase of the AA/EPA ratio in subjects who ran greater weekly distances (β = 0.092; 95% CI 0.038 to 0.146; R2 = 0.320; p = 0.001). No other significant associations were observed with other variables, including years of running training and weekly training frequency (hours/week). Finally, as expected, a significant inverse correlation between ω-3 index and AA/EPA ratio (β = −2.614; 95% CI −3.407 to −1.821; R2 = 0.336; p < 0.0001) was detected. Conclusions: These findings suggest that distance running training and its weekly volume may negatively contribute to changes of the ω-3 index and AA/EPA ratio. Further studies with greater sample size will be required to replicate and extend these data.

Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naive cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the role of nutrition and of immunomodulation in immunosenescence is discussed, due to the multifactorial influence on these hallmarks. The close connection between nutrition, intake of bioactive nutrients and supplements, immune function, and inflammation demonstrate the key role of dietary strategies as regulators of immune response and inflammatory status, hence as possible modulators of the rate of immunosenescence. In addition, potential options for therapeutic intervention are clarified. In particular, the use of interleukin-7 as growth factor for naive T cells, the function of checkpoint inhibitors in improving T cell responses during aging and, the potential of drugs that inhibit mitogen-activated protein kinases and their interaction with nutrient signaling pathways are discussed. Finally, it is suggested that the inclusion of appropriate combinations of toll-like receptor agonists may enhance the efficacy of vaccination in older adults.

Aim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p

Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation of cognitive function. A meta-analysis of randomized controlled trials was conducted to examine the relationship between carotenoid supplementation and cognitive performance. A literature search was conducted in the MEDLINE (via PubMed), Scopus, Web of Science, and Cochrane databases from their inception to July 2020. A total of 435 studies were retrieved. Abstract screening using predefined inclusion and exclusion criteria was followed by full-text screening and data extraction of study characteristics and measured outcomes. A meta-analysis of eligible trials was performed using a random-effects model to estimate pooled effect size. We identified 9 studies with a total of 4402 nondemented subjects, whose age ranged from 45 to 78 years. Results of the pooled meta-analysis found a significant effect of carotenoid intervention on cognitive outcomes (Hedge’s g = 0.14; 95 % confidence interval: 0.08, 0.20, p < 0.0001). There was no evidence of heterogeneity among the studies (τ2 = 0.00, I2 = 0.00%, H2 = 1.00) or publication bias. Although further studies are needed, our results suggest that carotenoid interventions are associated with better cognitive performance. Thus, these dietary compounds may help to reduce the risk of cognitive impairment and dementia.

The Mediterranean diet (MD) is a gold standard for nutrition and the most evidence-based diet to delay the onset of age-associated pathologies. Telomeres are the heterochromatic repeat regions found at the ends of eukaryotic chromosomes, whose length is considered a reliable hallmark of biological ageing. Telomere shortening is, at least in part, a modifiable factor and there is evidence that adherence to the MD is associated with longer telomeres. Data from several studies indicate an association between “inflammatory/oxidative status” and telomere length (TL). The MD, as a complex exposome with thousands of nutrients and phytochemicals, may positively influence telomere attrition by reducing inflammation and oxidative stress. However, it is unclear whether the protective effects on TL provided by the MD result from its individual constituents or some combination of these. Furthermore, these properties of the MD and its components are not yet fully validated by clinical endpoints in randomized trials or observational studies. Here, we summarize the data from experimental and population-based studies on the effects of the MD on TL maintenance. We will both highlight the possible role of the MD in the prevention of age-associated diseases, and attempt to identify certain aspects of the diet that are particularly important for telomere maintenance.

Background. Several dietary phytochemicals potentially regulate the equilibrium between oxidant and antioxidant species. The aim of this study was to evaluate the effects of Lippia citriodora, Raphanus sativus, and Solanum lycopersicum on blood parameters, oxidative/antioxidant status, and SIRT1 activity in the rabbit’s heart and liver. Methods. Twenty rabbits were divided into 4 groups of 5 animals each. The control group (CN) received a feed without any additives. One intervention group received a supplement containing verbascoside (VB), another Raphanus sativus extract (RAP), and lastly lycopene (LYC). Oxidant-antioxidant parameters and SIRT1 activity were measured in plasma and in the heart and liver, respectively. Results. The treatment with VB, RAP, and LYC resulted in a marked improvement in the blood lipid and glycaemic profile in respect to CN. VB was the most effective, but all three plant extracts induced a significant reduction in oxidant parameters as well as an increase in antioxidant tissue activity and vitamin A and E levels. SIRT1 activity was significantly increased in both VB and LYC compared to CN, but the increased levels in the VB group were far the highest. The multivariate analysis suggests that the benefits of VB, particularly the antiglycaemic and antioxidant effects, might be mediated by increasing SIRT1 activity.

The nervous system requires a high and continuous energy requirement and despite the brain represents only 2% of the body weight it receives about 15% of the cardiac output and consumes 20% of oxygen. The neuronal activity therefore determines a significant increase in energy consumption thus favoring the fact that the brain, during aging, becomes the seat of crucial structural and functional changes that condition the health in a fundamental way.

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.

Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health.

Ephedrine/caffeine combination (EC) has been shown to induce a small-to-moderate weight loss in obese patients. Several mechanisms have been proposed, among which an increased thermogenic capacity of skeletal muscle consequent to the EC-induced up-regulation of uncoupling protein 3 (UCP3) gene expression. We did a parallel group double-blind, placebo-controlled, 4-week trial to investigate this hypothesis. Thirteen morbidly obese women (25-52 years of age, body-mass index 48.0±4.0 kg/m2, range 41.1-57.6) were randomly assigned to EC (200/20 mg, n = 6) or to placebo (n = 7) administered three times a day orally, before undergoing bariatric surgery. All individuals had an energy-deficit diet equal to about 70% of resting metabolic rate (RMR) diet (mean 5769±1105 kJ/day). The RMR analysed by intention to treat and the UCP3 (long and short isoform) mRNA levels in rectus abdominis were the primary outcomes. Body weight, plasma levels of adrenaline, noradrenaline, triglycerides, free fatty acids, glycerol, TSH, fT4, and fT3 were assessed, as well as fasting glucose, insulin and HOMA index, at baseline and at the end of treatments. Body weight loss was evident in both groups when compared to baseline values (overall -5.2±3.2%, p

Nuclear Magnetic Resonance (NMR)-based metabonomics of EBC is able to separate healthy subjects from patients affected by Chronic Obstructive Pulmonary Disease (COPD), identifying profiles based on cellular oxidative pattern. It is unknown if EBC of COPD patients is altered by treatment of patients with specific exogenous nutrients, and if NMR spectroscopy is able to detect metabolic changes. In this preliminary open label study we evaluated the effect of daily oral administration of high dosage of a curcumin-based herbal preparation on EBC in a cohort of COPD patients by using NMR spectroscopy. 10 COPD (63.3 ± 7.9) patients were evaluated at baseline and after 12 weeks of oral administration of curcumin once a day, collecting during each visit EBC samples, clinical (breath, cough, sputum and night awakening, BSCN, score) data and spirometry. EBC collected from each patient (at the end of treatment and baseline) were different in NMR spectra profiles and in comparison with spectra of curcumin alone. Notably, a completely different profile is observed in treated patients, with many new resonances appearing in the spectra. Among clinical parameters, BSCN score was 4.9 ± 0.9 at baseline and 7.5 ± 1.0 at time 12 wks, while FEV1 values resulted slightly but not significantly increased at the end of treatment. NMR metabonomic is a sensitive method to explore the nutriceutic effects of antioxidant on EBC in patients of COPD.