Extending healthy ageing: nutrient sensitive pathway and centenarian population

Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation

A Randomized Clinical Trial Evaluating the Efficacy of an Anthocyanin–Maqui Berry Extract (Delphinol®) on Oxidative Stress Biomarkers

Objective: Berries are a rich source of anthocyanins, and clinical data suggest that a polyphenol-rich diet may exert health-promoting effects by reducing oxidative stress. The aim of this study was to elucidate the effects of dietary supplementation with Delphinol (trademark owned by MNL Chile) standardized maqui berry (Aristotelia chilensis) extract on products of lipid peroxidation in healthy, overweight, and smoker subjects.Methods: In a double-blind, placebo-controlled design, 42 participants (age 45-65years) consumed in random order either a standardized extract of maqui berry (162mg anthocyanins) or a matched placebo, given 3times daily for 4weeks. The samples were collected at baseline, after the end of the supplementation, and 40days after the end of the study. Primary outcome was the measure of oxidized low-density lipoprotein (Ox-LDL) and F-2-isoprostanes in plasma and urine, respectively. Secondary outcomes included anthropometric measures, blood pressure, and lipid profile.Results: Delphinol supplementation was associated with reduced levels of Ox-LDL in the anthocyanin group compared to baseline (p < 0.05). There was also a decrease in urinary F-2-isoprostanes (8-iso-prostaglandin F2) at 4weeks versus baseline in the Delphinol-supplemented group (p < 0.05). However, no differences in primary outcomes were evident at 40days of follow-up. In the fourth week of the intervention, no significant differences were noted for anthropometric characteristics, ambulatory blood pressure, and lipid profile.Conclusions: Our observations suggest that dietary interventions with maqui berry extract may improve oxidative status (Ox-LDL and F-2-isoprostanes) in healthy adults, overweight adults, and adult smoke

Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

Alzheimer's disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD

Dietary phytochemicals and neuro-inflammaging: From mechanistic insights to translational challenges

An extensive literature describes the positive impact of dietary phytochemicals on overall health and longevity. Dietary phytochemicals include a large group of non-nutrients compounds from a wide range of plant-derived foods and chemical classes. Over the last decade, remarkable progress has been made to realize that oxidative and nitrosative stress (O&NS) and chronic, low-grade inflammation are major risk factors underlying brain aging. Accumulated data strongly suggest that phytochemicals from fruits, vegetables, herbs, and spices may exert relevant negative immunoregulatory, and/or anti-O&NS activities in the context of brain aging. Despite the translational gap between basic and clinical research, the current understanding of the molecular interactions between phytochemicals and immune-inflammatory and O&NS (IO&NS) pathways could help in designing effective nutritional strategies to delay brain aging and improve cognitive function. This review attempts to summarise recent evidence indicating that specific phytochemicals may act as positive modulators of IO&NS pathways by attenuating pro-inflammatory pathways associated with the age-related redox imbalance that occurs in brain aging. We will also discuss the need to initiate long-term nutrition intervention studies in healthy subjects. Hence, we will highlight crucial aspects that require further study to determine effective physiological concentrations and explore the real impact of dietary phytochemicals in preserving brain health before the onset of symptoms leading to cognitive decline and inflammatory neurodegeneration

Crosslinked Hyaluronic Acid with Liposomes and Crocin Confers Cytoprotection in an Experimental Model of Dry Eye

Dry eye disease (DED) is a multifactorial condition caused by tear deficiency and accompanied by ocular surface damage. Recent data support a key role of oxidative and inflammatory processes in the pathogenesis of DED. Hyaluronic acid (HA) is widely used in artificial tears to treat DED by improving ocular hydration and reducing surface friction. Crocin (Cr), the main constituent of saffron, is a renowned compound that exhibits potent antioxidant and anti-inflammatory effects. The present study was undertaken to assess the viscosity and muco-adhesiveness of a photoactivated formulation with crosslinked HA (cHA), Cr, and liposomes (cHA-Cr-L). Our aim was also to evaluate whether cHA-Cr-L may exert cytoprotective effects against oxidative and inflammatory processes in human corneal epithelial cells (HCECs). Viscosity was measured using a rotational rheometer, and then the muco-adhesiveness was evaluated. Under hyperosmolarity (450 mOsm), the HCECs were treated with cHA-Cr-L. Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). The levels of reactive oxygen species (ROS) were measured using the DCF assay. The combined action of cHA-Cr-L produced a higher viscosity and muco-adhesiveness compared to the control. The anti-inflammatory effect of cHA-Cr-L was achieved through a significant reduction of IL-1beta and TNFalpha (p &lt; 0.001). The results also showed that cHA-Cr-L reduces ROS production under conditions of hyperosmolarity (p &lt; 0.001). We conclude that cHA-Cr-L has potential as a therapeutic agent in DED, which should be further investigated

Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate

The medical community recognizes sex-related differences in pathophysiology and cardiovascular disease outcomes (CVD), culminating with heart failure. In general, pre-menopausal women tend to have a better prognosis than men. Explaining why this occurs is not a simple matter. For decades, sex hormones like estrogens (Es) have been identified as one of the leading factors driving these sex differences. Indeed, Es seem protective in women as their decline, during and after menopause, coincides with an increased CV risk and HF development. However, clinical trials demonstrated that E replacement in post-menopause women results in adverse cardiac events and increased risk of breast cancer. Thus, a deeper understanding of E-related mechanisms is needed to provide a vital gateway toward better CVD prevention and treatment in women. Of note, sphingolipids (SLs) and their metabolism are strictly related to E activities. Among the SLs, ceramide and sphingosine 1-phosphate play essential roles in mammalian physiology, particularly in the CV system, and appear differently modulated in males and females. In keeping with this view, here we explore the most recent experimental and clinical observations about the role of E and SL metabolism, emphasizing how these factors impact the CV system

The "Alzheimer's disease signature": potential perspectives for novel biomarkers

Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support clinical diagnosis and provide discriminatory power between different stages of the disorder. A considerable challenge is to integrate different types of data from new potent approach to reach a common interpretation and replicate the findings across studies and populations. Furthermore, long-term clinical follow-up and combined analysis of several biomarkers are among the most promising perspectives to diagnose and manage the disease. The present review will focus on the recent published data providing an updated overview of the main achievements in the genetic and biochemical research of the Alzheimer's disease. We also discuss the latest and most significant results that will help to define a specific disease signature whose validity might be clinically relevant for future AD diagnosis

Ventricular Dyssynchrony: 12-month Evaluation In Ischemic Versus Nonischemic CRT Patients

Objective: Few data exist about the potential differences in the dyssynchrony status of cardiac resynchronization therapy (CRT) candidates stratified by etiology of heart failure, and about the evolution of dyssynchrony at long-term follow-up. We provided a description of intra-ventricular dyssynchrony at baseline, 6 months and 12 months in ischemic and nonischemic CRT patients.Methods: Tissue Doppler Imaging was performed in 35 CRT candidates (18 ischemic, 17 nonischemic) at baseline, and at 6-month and 12-month follow-up. A group of 11 healthy subjects was considered for comparison.Results: At baseline, the standard deviation and the maximum activation delay between any 2 segments were significantly greater in ischemic (38±33ms, 94±76ms) and nonischemic (38±24ms, 96±62ms) patients versus controls (9±7ms, 22±15ms) (all p<0.05). The average time to activation for posterior and lateral wall was significantly higher in nonischemic patients, while the anterior septum activated later in ischemic patients. At 6-month follow-up, standard deviation and maximum delay did not vary in nonischemic while decreased in ischemic group. All changes persisted at 12 months.Conclusions No baseline differences were observed between ischemic and nonischemic patients using studied indices. At 6- and 12-month follow-up, only ischemic patients presented a significant reduction in dyssynchrony values, although in both groups CRT did not lead to a complete normalization of LV synchronism

Relationship Between Distance Run Per Week, Omega-3 Index, and Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio: An Observational Retrospective Study in Non-elite Runners

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 &lt; 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 &lt; 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