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The large, randomized, double-blind, placebo-controlled trial VITAL (Vitamin D and omega 3 trial) recently confirmed that vitamin D and omega-3 polyunsaturated fatty acid (PUFA) co-supplementation (VIDOM) can reduce the incidence of autoimmune diseases. Based on these relevant results, this commentary summarizes the molecular mechanisms behind the anti-inflammatory and immunomodulatory properties of vitamin D and omega-3 PUFAs. We also describe the potential bidirectional interplay between vitamin D metabolism and omega-3 PUFA metabolism that underlies the rationale for VIDOM co-supplementation and that may contribute to enhance the anti-inflammatory and immunomodulatory actions of vitamin D and omega-3 PUFAs when these compounds are administered in combination.

The aim of this study was to assess the impact of glucose control, diabetes-related complications and cardiometabolic risk factors on the risk of diabetic foot ulcers (DFUs) and DFU complications in Albanian adult inpatients with T2D.We conducted a retrospective case-control study on 482 Albanian adult inpatients with T2D. DFU was defined as a full-thickness skin lesion requiring ≥14 days for healing and was classified at the time of hospital admission. Demographic and biochemical parameters of the study participants, the presence of comorbidities and diabetes-related complications at the time of hospital admission were evaluated through a retrospective chart review.Mean age of study participants was 54.8±10.7 years. Participants (284 males and 198 females) were divided into two groups: DFU (cases; n=104) and non-DFU (controls; n=378). Multivariate analysis (performed by a logistic regression model) revealed that the most relevant independent variables associated with DFU were BMI [OR=0.62; p=0.007], HDL-cholesterol [OR=0.00; p0.0001], triglycerides [OR=7.48; p=0.0004], cigarette smoking [OR=26.46; p=0.005], duration of diabetes [OR=1.53; p0.0001], fasting plasma glucose (FPG) [OR=1.06; p0.0001], systolic blood pressure (SBP) [OR=1.13; p=0.0004] and insulin therapy alone [OR=0.11; p=0.02]. ROC curve analysis showed that FPG (AUC=0.83), glycated hemoglobin (HbA1c) (AUC=0.75), triglycerides (AUC=0.78) and HDL-cholesterol (AUC=0.82) were the most reliable biomarkers able to detect DFU. In the DFU group, the most relevant independent variables associated with previous minor lower-extremity amputations (LEAs) were represented by HbA1c [OR=1.47; p=0.03], age55 years [OR=0.12; p=0.05] and female sex [OR=4.18; p=0.03]; whereas the most relevant independent variables associated with diabetic peripheral neuropathy (DPN) were HbA1c [OR=1.70; p=0.006], SBP [OR=1.08; p=0.05], BMI [OR=1.20; p=0.03] and lack of cigarette smoking [OR=0.07; p=0.01]. Correlation analysis (performed through the nonparametric Spearman's rank correlation test or through the parametric Pearson test, as appropriate) revealed a significant positive relationship between HbA1c and FPG (r=0.58; p0.0001), ulcer surface area (r=0.50; p0.0001), ulcer grade (r=0.23; p=0.02), minor LEAs (r=0.20; p=0.04), DPN (r=0.41; p0.0001), and metformin therapy alone (r=0.72; p0.0001). There was a significant inverse correlation between HbA1c and insulin therapy alone (r=-0.31; p=0.01) and combined metformin and insulin therapy (r=-0.60; p0.0001). Both DFU and non-DFU groups exhibited suboptimal mean LDL-cholesterol levels (100 mg/dl) and mean HbA1c values7.5%. Moreover, in DFU group HbA1c values were markedly elevated (≥10%) particularly in patients with a grade 3 ulcer and an ulcer surface area ≥4 cm2, as well as in patients with history of minor LEAs and in patients affected by DPN.The present study suggested that longer duration of diabetes, cigarette smoking, lower HDL-cholesterol levels, poor glucose control, and elevated triglyceride and SBP values may all represent major risk factors for the development of DFU in Albanian patients with T2D. Thus, community interventions and health policies aimed to improve the management of diabetes and related cardiometabolic risk factors should be urgently implemented in Albania, in order to prevent DFUs and other diabetes complications in patients with T2D.

The role of atenolol, a non-vasodilating beta-blocker drug, on long-term mortality in hypertensive older adults is still unclear. The aim of the present study was to evaluate long-term mortality in community-dwelling hypertensive older adults taking atenolol.Long-term mortality after 12-year follow up in isolated hypertensive older adults (n = 972) was analyzed. The patients were stratified in the presence and absence of atenolol use. Systolic, diastolic and pulse arterial pressure were measured.Older adults taking atenolol showed a greater mortality and higher pulse arterial pressure values than those not taking atenolol (73.9% vs 55.0%; P = 0.047 and 74.7 ± 14.1 vs 63.0 ± 14.2 mmHg, P 0.001, respectively). Cox regression analysis showed that atenolol use (hazard risk 1.91; 95% confidence interval 1.04-4.31; P = 0.04) and pulse arterial pressure (hazard risk 1.02; 95% confidence interval 1.01-1.03; P = 0.032) were predictive of long-term mortality.Atenolol use was related to increased mortality in community-dwelling hypertensive Older adults. This increase in mortality risk seems to be related to an increase of pulse arterial pressure.

The growing demand of personalized medicine marked the transition from an empirical medicine to a molecular one, aimed at predicting safer and more effective medical treatment for every patient, while minimizing adverse effects. This passage has emphasized the importance of biomarker discovery studies, and has led sample availability to assume a crucial role in biomedical research. Accordingly, a great interest in Biological Bank science has grown concomitantly. In biobanks, biological material and its accompanying data are collected, handled and stored in accordance with standard operating procedures (SOPs) and existing legislation. Sample quality is ensured by adherence to SOPs and sample whole life-cycle can be recorded by innovative tracking systems employing information technology (IT) tools for monitoring storage conditions and characterization of vast amount of data. All the above will ensure proper sample exchangeability among research facilities and will represent the starting point of all future personalized medicine-based clinical trials.

Background Chronic heart failure (CHF) is characterized by a high mortality in the elderly. Moreover, depression status is also related to poor prognosis in advancing age. Thus, we sought to determine whether depressive status predicts long-term mortality in subject with or without CHF. Methods and results Long-term mortality after 12-year follow-up in 125 elderly subjects with CHF and 1143 elderly subjects without CHF was studied. Depression was evaluated using the Geriatric Depression Scale (GDS), and all subjects were stratified in tertiles according to GDS score (0–10, 11–20 and 21–30). With increasing GDS score, long-term mortality at the end of follow-up increased from 43Æ4% to 72Æ0% in subjects without (P < 0Æ001) and from 52Æ6% to 83Æ9% in subjects with (P < 0Æ007) CHF. In multivariate analysis, GDS appeared to be predictive of long-term mortality in the absence (Hazard ratio = 1Æ01; confidence interval 95% 1Æ00–1Æ05; P = 0Æ04) and, even more, in the presence of CHF (Hazard ratio = 1Æ08; confidence interval 95% 1Æ01–1Æ15; P < 0Æ01). Conclusions Depression symptoms predict long-term mortality in elderly subjects without and, even more, with CHF. Thus, depression can be considered a strong predictor of death in CHF elderly subjects.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the digestive tract characterized, in the majority of cases, by activating mutations in the KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) genes. Mutations affecting these tyrosine kinase receptors are also responsible for the mechanisms of primary and secondary drug resistance during the treatment with tyrosine kinase inhibitors. We performed mutational analysis to evaluate the pharmacotherapy susceptibility of GISTs, adopting a comprehensive procedural approach, in order to optimize the identification of mutations that may result in cellular resistance to conventional therapy.DNA from paraffin-embedded tumor sections from 40 GISTs were analyzed using microdissection, direct sequencing analysis and allelic separation by cloning.KIT mutations were found in 55.0% of the tumor samples. PDGFRA mutations were present in 5.0% of cases. Allelic cloning assay allowed for better definition of the extent of the mutations and clarification of the exact nucleotidic position of complex mutations.Our experience suggests that sequential microdissection, direct sequencing and allelic separation by PCR cloning of large variants may improve the approach to mutational analysis and interpretation of sequence data of KIT and PDGFRA in patients with GIST.

International audience; Cell-based therapies for global cerebral ischemia represent promising approaches for neuronal damage prevention and tissue repair promotion. We examined the potential of marrow-isolated adult multilineage-inducible (MIAMI) cells, a homogeneous subpopulation of immature human mesenchymal stromal cell, injected into the hippocampus to prevent neuronal damage induced by global ischemia using rat organotypic hippocampal slices exposed to oxygen-glucose deprivation and rats subjected to asphyxial cardiac arrest. We next examined the value of combining fibronectin-coated biomimetic microcarriers (FN-BMMs) with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) pre-treated MIAMI compared to EGF/bFGF pre-treated MIAMI cells alone, for their in vitro and in vivo neuroprotective capacity. Naive and EGF/bFGF pre-treated MIAMI cells significantly protected the Cornu Ammonis layer 1 (CA1) against ischemic death in hippocampal slices and increased CA1 survival in rats. MIAMI cells therapeutic value was significantly increased when delivering the cells complexed with FN-BMMs, probably by increasing stem cell survival and paracrine secretion of pro-survival and/or anti-inflammatory molecules as concluded from survival, differentiation and gene expression analysis. Four days after oxygen and glucose deprivation and asphyxial cardiac arrest, few transplanted cells administered alone survived in the brain whereas stem cell survival improved when injected complexed with FN-BMMs. Interestingly, a large fraction of the transplanted cells administered alone or in complexes expressed betaIII-tubulin suggesting that partial neuronal transdifferentiation may be a contributing factor to the neuroprotective mechanism of MIAMI cells.

Mutations in the Kirsten Ras 1 (KRAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) genes may be predictive of response to drugs directly linked to the Epidermal Growth Factor Receptor (EGFR) signaling pathway.A total of 230 samples from patients with metastatic colorectal cancer were analyzed for KRAS exon 1 and 2 and for BRAF exon 15 mutations. DNA from paraffin-embedded tumor sections was analyzed using microdissection, direct sequencing analysis and allelic separation by cloning.KRAS mutations were present in 44.3% of the tumor samples. The mutation frequency at hot-spot codons of exon 1 was 84.2%, whereas non-canonical variants had a frequency of 11.8%. Approximately 4% of the cases exhibited concomitant variations. BRAF mutations were present in 3.9% of the tumor samples.Our experience suggests that sequential microdissection, direct sequencing and allelic separation by cloning may improve the approach to mutational analysis of KRAS and BRAF in patients with colorectal cancer.

Epidemiologic studies have documented an association between diabetes and increased risk of cognitive decline in the elderly. Based on animal model studies, several mechanisms have been proposed to explain such an association, including central insulin signaling, neurodegeneration, brain amyloidosis, and neuroinflammation. Nevertheless, the exact mechanisms in humans remain poorly defined. It is reasonable, however, that many pathways may be involved in these patients leading to cognitive impairment. A major aim of clinicians is identifying early onset of neurologic signs and symptoms in elderly diabetics to improve quality of life of those with cognitive impairment and reduce costs associated with long-term complications. Several biomarkers have been proposed to identify diabetics at higher risk of developing dementia and diagnose early stage dementia. Although biomarkers of brain amyloidosis, neurodegeneration and synaptic plasticity are commonly used to diagnose dementia, especially Alzheimer disease, their role in diabetes remains unclear. The aim of this review is to explore the molecular mechanisms linking diabetes with cognitive decline and present the most important findings on the clinical use of biomarkers for diagnosing and predicting early cognitive decline in diabetics.

Objective: It is a common belief that menopausal women have greater difficulty losing weight. The aim of this study was to assess the efficacy of a Mediterranean diet (MD) to promote weight loss in postmenopausal women. All participants were prescribed a hypocaloric traditional MD, tailored to the individual. Subjects were asked not to begin any kind of physical activity. Body composition was measured at the beginning and after 8 weeks of treatment. In total, 89 women (age 52.8 &plusmn, 4.5 years, BMI 30.0 &plusmn, 5.2 kg/m2, fat mass 31.6 &plusmn, 10.5 kg) were divided into two groups: the first group consisted of fertile women over 45 years of age, the second group consisted of those diagnosed as menopausal. All women had an improvement in body composition (fat mass &minus, 2.3 &plusmn, 2.1 kg, p &lt, 0.001, protein &minus, 0.1 &plusmn, 0.7 kg, p = 0.190) and blood pressure values. No differences were found between the two groups except for a higher reduction of low-density lipoprotein in the menopausal group (p = 0.035). A positive significant correlation between plant to animal protein ratio and fat-free mass variation was found in the menopausal group. These data suggest that a high adherence to a traditional MD would enable menopausal women to lose fat mass and maintain muscle mass with no significant difference to younger women. Fat mass reduction provides menopausal women with improved cardiovascular and metabolic risk factors.

Aims The assessment of frailty in older adults with heart failure (HF) is still debated. Here, we compare the predictive role and the diagnostic accuracy of physical vs. multidimensional frailty assessment on mortality, disability, and hospitalization in older adults with and without HF. Methods and results A total of 1077 elderly (≥65 years) outpatients were evaluated with the physical (phy‐Fi) and multidimensional (m‐Fi) frailty scores and according to the presence or the absence of HF. Mortality, disability, and hospitalizations were assessed at baseline and after a 24 month follow‐up. Cox regression analysis demonstrated that, compared with phy‐Fi score, m‐Fi score was more predictive of mortality [hazard ratio (HR) = 1.05 vs. 0.66], disability (HR = 1.02 vs. 0.89), and hospitalization (HR = 1.03 vs. 0.96) in the absence and even more in the presence of HF (HR = 1.11 vs. 0.63, 1.06 vs. 0.98, and 1.14 vs. 1.03, respectively). The area under the curve indicated a better diagnostic accuracy with m‐Fi score than with phy‐Fi score for mortality, disability, and hospitalizations, both in absence (0.782 vs. 0.649, 0.763 vs. 0.695, and 0.732 vs. 0.666, respectively) and in presence of HF (0.824 vs. 0.625, 0.886 vs. 0.793, and 0.812 vs. 0.688, respectively). Conclusions The m‐Fi score is able to predict mortality, disability, and hospitalizations better than the phy‐Fi score, not only in absence but also in presence of HF. Our data also demonstrate that the m‐Fi score has better diagnostic accuracy than the phy‐Fi score. Thus, the use of the m‐FI score should be considered for the assessment of frailty in older HF adults.

Modifications of lean mass are a frequent critical determinant in the pathophysiology and progression of heart failure (HF). Sarcopenia may be considered one of the most important causes of low physical performance and reduced cardiorespiratory fitness in older patients with HF. Sarcopenia is frequently misdiagnosed as cachexia. However, muscle wasting in HF has different pathogenetic features in sarcopenic and cachectic conditions. HF may induce sarcopenia through common pathogenetic pathways such as hormonal changes, malnutrition, and physical inactivity; mechanisms that influence each other. In the opposite way, sarcopenia may favor HF development by different mechanisms, including pathological ergoreflex. Paradoxically, sarcopenia is not associated with a sarcopenic cardiac muscle, but the cardiac muscle shows a hypertrophy which seems to be “not-functional.” First-line agents for the treatment of HF, physical activity and nutritional interventions, may offer a therapeutic advantage in sarcopenic patients irrespective of HF. Thus, sarcopenia is highly prevalent in patients with HF, contributing to its poor prognosis, and both conditions could benefit from common treatment strategies based on pharmacological, physical activity, and nutritional approaches.

Purpose of Review: The aim of this review is to evaluate the ideal protein quality and quantity and the dietary composition for the prevention and metabolic control of type 2 diabetes mellitus (T2DM). Introduction: Although some reviews demonstrate the advantages of a diet with a higher protein intake, other reviews have observed that a diet high in carbohydrates, with low-glycaemic index carbohydrates and good fibre intake, is equally effective in improving insulin sensitivity. Methods: Over 2831 articles were screened, and 24 from the last 5years were analysed and summarised for this review, using the protein, diabetes and insulin glucose metabolic keywords in Pubmed in June 2019. Results: Eleven studies demonstrate that a higher consumption of proteins has a positive effect on insulin sensitivity. A higher intake of animal protein seems to be related to an increased risk of T2DM. Four studies show that consumption of meat has a deleterious effect. Higher intake of plant protein and dairy products is associated with a modestly reduced risk. Discussion: Based on the results obtained, for the prevention of T2DM and all disorders related to metabolic syndrome, no ideal dietary composition has yet been found. The advantage of plant protein sources may be related to the foods’ low-glycaemic index due to the high fibre content. However, the right protein quality (animal and plant) and the quantity for T2DM prevention and metabolic control are unclear and need to be investigated with further long-term studies.

Ilaria Liguori,1 Gennaro Russo,1 Francesco Curcio,1 Giulia Bulli,1 Luisa Aran,1 David Della-Morte,2,3 Gaetano Gargiulo,4 Gianluca Testa,1,5 Francesco Cacciatore,1,6 Domenico Bonaduce,1 Pasquale Abete1 1Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy; 2Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 3San Raffaele Roma Open University, Rome, Italy; 4Division of Internal Medicine, AOU San Giovanni di Dio e Ruggi di Aragona, Salerno, Italy; 5Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy; 6Azienda Ospedaliera dei Colli, Monaldi Hospital, Heart Transplantation Unit, Naples, Italy Abstract: Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer), including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of several diseases, but further investigation is needed to evaluate the real efficacy of these therapeutic interventions. The purpose of this paper is to provide a review of literature on this complex topic of ever increasing interest. Keywords: elderly, reactive oxygen species, reactive nitrogen species, antioxidants

Type 2 myocardial infarctions (T2-MI) is a type of necrosis that results from reduced oxygen supply and/or increased demand secondary to other causes unrelated to acute coronary atherothrombosis. The development and implementation of sensitive and high-sensitivity cardiac necrosis marker and the age-related increase of comorbidity lead to a boost of the frequency of T2-MI. T2-MI is often a complication of a high degree of clinical frailty in older adults, emerging as a "geriatric syndrome". Age-related non-cardiovascular causes may be the triggering factors and are strongly associated with the diagnosis, treatment, and prognosis of T2-MI. To date, there are no guidelines on management of this pathology in advancing age. Patient-centered approach and comprehensive geriatric assessment play a key role in the diagnosis, therapy and prognosis of geriatric patients with T2-MI.

Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases enzymes (SIRT1−7) that play an important role in maintaining cellular homeostasis. Among those, the most studied are SIRT1 and SIRT3, a nuclear SIRT and a mitochondrial SIRT, respectively, which significantly impact with an increase in mammals’ lifespan by modulating metabolic cellular processes. Particularly, when activated, both SIRT1 and 3 enhance pancreatic β-cells’ insulin release and reduce inflammation and oxidative stress pancreatic damage, maintaining then glucose homeostasis. Therefore, SIRT1 and 3 activators have been proposed to prevent and counteract metabolic age-related diseases, such as type 2 diabetes mellitus (T2DM). Physical activity (PA) has a well-established beneficial effect on phenotypes of aging like β-cell dysfunction and diabetes mellitus. Recent experimental and clinical evidence reports that PA increases the expression levels of both SIRT1 and 3, suggesting that PA may exert its healthy contribute even by activating SIRTs. Therefore, in the present article, we discuss the role of SIRT1, SIRT3, and PA on β-cell function and on diabetes. We also discuss the possible interaction between PA and activation of SIRTs as a possible therapeutic strategy to maintain glucose hemostasis and to prevent T2DM and its complications, especially in the elderly population.

Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s Disease (AD) and cerebral ischemia. Specifically ε, δ, and γPKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of εPKC, such as ψεReceptor for Activated C-Kinase (ψεRACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing εPKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of δPKC and γPKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration.

Chronic heart failure (CHF) is frequently linked to clinical frailty, a complex geriatric condition associated with negative outcomes. However, the full characterization of frailty is still debated. Fried and colleagues focused on a ‘physical phenotype’ of frailty based on the assessment of unintentional weight loss, muscle weakness, slow walking speed, low physical activity, and exhaustion,1 while Rockwood and colleagues fostered a multidimensional concept involving, besides physical impairments, comorbidity, disability, mental, nutritional, and social components (known as the ‘Canadian frailty index’).

BACKGROUND: Orthostatic hypotension (OH) has high prevalence in frail older adults. However, its effect on mortality, disability, and hospitalization in frail older adults is poorly investigated. Thus, we assessed the relationship between the prevalence of OH and its effect on mortality, disability, and hospitalization in noninstitutionalized older adults stratified by frailty degree. METHODS: Prospective, observational study of 510 older participants (≥65 years of age) consecutively admitted to a geriatric evaluation unit to perform a geriatric comprehensive assessment. MEASUREMENTS: Clinical frailty was assessed using the Italian frailty index (40 items). Systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg), and heart rate (bpm) were evaluated in clinostatic position and after 1, 3, and 5 minutes of orthostatic position. OH was defined with a decrease of 20 mm Hg in systolic blood pressure and/or a decrease of 10 mm Hg in diastolic blood pressure. RESULTS: OH prevalence was 22%, and it increased from 9.0% to 66.0% according to frailty degree (P for trend

BACKGROUND: Malnutrition indices and muscle mass and strength in the elderly are poorly investigated. Moreover, malnutrition seems to be 1 of the more important factors in the cause of sarcopenia. The presence of sarcopenia and its relationship with malnutrition indices were studied in noninstitutionalized elderly people who underwent Comprehensive Geriatric Assessment (CGA). METHODS: A total of 473 elderly subjects (mean age, 80.9 ± 6.6 years) admitted to CGA were studied. Malnutrition risk was evaluated with Mini Nutritional Assessment (MNA) score, whereas muscle mass and muscle strength were evaluated by bioimpedentiometry and hand grip, respectively. Sarcopenia was assessed as indicated in the European Working Group on Sarcopenia in Older People (EWGSOP) consensus. RESULTS: Overall prevalence of sarcopenia was 13.1%, and it increased from 6.1% to 31.4% as MNA decreased (P < .001). MNA score was lower in elderly subjects with sarcopenia (15.4 ± 4.2) than without sarcopenia (22.0 ± 4.0) (P = .024). Linear regression analysis showed that MNA score is linearly related both with muscle mass (r = 0.72; P < .001) and strength (r = 0.42; P < .001). Multivariate analysis, adjusted for several confounding variables including comorbidity and disability, confirmed these results. CONCLUSIONS: MNA score is low in noninstitutionalized elderly subjects with sarcopenia, and it is linearly related to muscle mass and muscle strength. These data indicate that MNA score, when evaluated with muscle mass and strength, may recognize elderly subjects with sarcopenia.

The traditional model of care is based on "disease-centered" management that requires the organization of the hospital in specialized wards, to which the patient is assigned for the main disease. The growing need to optimize economical and human resources and to promote a global approach to the patient has led to the setting up of the intensity of care model. It is a health system based on a "patient-centered" approach, where the hospital is organized in departments dedicated to patients with homogenous needs of care. In Italy, intensity of care model is currently being tested in the hospital organization, where three levels of intensity are proposed: low, medium and high. The purpose of the following review is to describe the role and importance of the Geriatrician in each of these care settings and to highlight the contradiction of a National Health System which promotes the geriatric approach to all types of patients, but does not invest in the formation and integration of the figure of the Geriatrician in clinical practice, condemning it to marginalization or even extinction.

Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure are also found to relate to outcomes in the geriatric population, but in a differing direction. A higher body mass index, hypercholesterolemia and hypertension are not harmful but even permit better survival at advancing age. This phenomenon is called "reverse epidemiology" or "risk factor paradox" and is also detected in a variety of chronic disease states such as chronic heart failure. Accordingly, a low BMI, blood pressure and cholesterol values are associated with a worse prognosis. Several possible causes are hypothesized to explain this elderly paradox, but this phenomenon remains controversial and its underlying reasons are poorly understood. The aim of this review is to recognize the factors behind this intriguing phenomenon and analyse the consequences that it can bring in the management of the cardiovascular therapy in elderly patient. Finally, a new phenotype identified as "catabolic syndrome" has been postulated.

Cerebrovascular disease (CeVD) is one of the major causes of death and a leading cause of disability worldwide. CeVD is a complex and multifactorial disease caused by the interaction of environment and genetic factors. Women have lower CeVD incidence than men until an advanced age, when the incidence of CeVD rises dramatically in women. Therefore, sex has been validated as an important risk factor in the etiology of CeVD, especially ischemic stroke. Although the importance of sex steroids have been heavily studied in the mechanism of neuronal injury, the experimental and clinical data suggest that hormones do not fully account for male versus female CeVD patterns. Sex-specific genetic processes have been implicated in the different rate of risk for atherosclerosis and CeVD. In this review, we discuss sex-specific CeVD processes, describe the hormonal impact on the risk for CeVD, the results from studies in transgenic animals, and from human genetic studies. Moreover, heritability of ischemic stroke in women and men as well as identification of possible sex-specific biomarkers for CeVD are discussed. Understanding the complex interactions between hormonal and genetic mechanisms in the CeVD risk will allow for new sex-specific approaches in disease treatment and prevention in clinical practice.

Background and Purpose: Sarcopenia, a loss of muscle mass and strength accompanying aging, is common in older adults who are not physically active. Nevertheless, the association between physical activity and sarcopenia has not been extensively studied. Therefore, we examined the relationship of both muscle mass and muscle strength with physical activity as quantified using the Physical Activity Scale for Elderly (PASE). Methods: PASE score, muscle mass by bioimpendiometry, and muscle strength by handgrip were evaluated in a cohort study of 420 older adult participants (mean age 82.4 [5.9] years), admitted to the Comprehensive Geriatric Assessment Center. Sarcopenia was assessed as indicated in the European Working Group on Sarcopenia in Older People (EWGSOP) consensus. Results: PASE score was lower in sarcopenic (40.2 [89.0]) than in non-sarcopenic (92.0 [52.4]) older adults (P < .001). Curvilinear regression analysis demonstrated that PASE score is related with muscle mass (R-2 = 0.63; P < .001) and strength (R-2 = 0.51; P < .001). Conclusions: The present study indicates that PASE score is curvilinearly related to muscle mass and strength and that low PASE score identifies sarcopenic noninstitutionalized older adults. This evidence suggests that PASE score evaluated together with muscle mass and strength may identify older adults at high risk of sarcopenia.

The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized. © 2014 Elsevier B.V.

OBJECTIVE Elderly subjects are characterized by a high prevalence of OA and clinical frailty. This study aimed to examine the predictive role of clinical frailty on long-term mortality in elderly subjects with and without OA. METHODS Mortality was evaluated after a 12-year follow-up in 698 subjects with and 590 subjects without OA recruited in 1992. Clinical frailty was assessed according to the Frailty Staging System and stratified in tertiles. RESULTS After a 12-year follow-up, mortality was 42.2% in subjects without and 55.8% in subjects with OA (P = 0.256). With increasing frailty, mortality increased by 30.5% (P for trend < 0.001) in subjects without and by 45.6% in subjects with OA (P for trend < 0.001). Multivariate analysis showed that frailty [hazard ratio (HR) = 1.49 for each unit of increase, 95% CI 1.32, 1.94, P < 0.001) but not OA (HR = 1.28, 95% CI 0.987, 1.39, P = 0.412) was predictive of long-term mortality. Moreover, when Cox regression analysis was performed, frailty enhanced the risk of long-term mortality for each unit of increase by 32% (HR = 1.32, 95% CI 1.06, 1.65, P = 0.03) in the absence of OA and by 98% in the presence (HR = 1.98, 95% CI 1.63, 2.95, P < 0.01) of OA. CONCLUSION Clinical frailty significantly predicts mortality in subjects without OA and even more in those with OA. Thus clinical frailty may be considered a new prognostic factor to identify subjects with OA at high risk of mortality.

BACKGROUND AND AIM: Several measurements were taken for frailty classification in geriatric population. "Frailty index" is based on "deficits in health," but it is still not available in Italian version. Thus, the aim of the present work was to validate a version of "frailty index" for the Italian geriatric community. METHODS: The validation of Italian frailty index (IFi) is based on a cohort study that enrolled 1077 non-disabled outpatients aged 65 years or older (81.3 ± 6.5 years) in Naples (Italy). IFi has been expressed as a ratio of deficits present/deficits considered after a comprehensive geriatric assessment. IFi was stratified in light, moderate and severe frailty. Mortality, disability (considering an increase in ADL lost ≥1 from the baseline) and hospitalization were considered at 3, 6, 12, 18 and 24 months of follow-up. Area under curve (AUC) was evaluated for both Fried's and IFi frailty index. RESULT: At the end of follow-up, mortality increased from 1.0 to 30.3%, disability from 40.9 to 92.3% and hospitalization from 0.0 to 59.0% (p < 0.001 for trend). Multivariate analysis shows that the relative risk for unit increase in IFi is 1.09 (95% CI = 1.01-1.17, p = 0.013) for mortality, 1.04 (95% CI = 1.01-1.06, p = 0.024) for disability and 1.03 (95% CI = 1.01-1.07, p = 0.041) for hospitalization. AUC is higher in IFi with respect to Fried's frailty index when considering mortality (0.809 vs. 0.658, respectively), disability (0.800 vs. 0.729, respectively) and hospitalization (0.707 vs. 0.646, respectively). CONCLUSIONS: IFi is a valid measure of frailty after the comprehensive geriatric assessment in an Italian cohort of non-institutionalized patients.

The slow and continuous loss of muscle mass that progresses with aging is defined as "sarcopenia". Sarcopenia represents an important public health problem, being closely linked to a condition of frailty and, therefore, of disability. According to the European Working Group on Sarcopenia in Older People, the diagnosis of sarcopenia requires the presence of low muscle mass, along with either low grip strength or low physical performance. However, age-related changes in skeletal muscle can be largely attributed to the complex interactions among factors including alterations of the neuromuscular junction, endocrine system, growth factors, and muscle proteins turnover, behavior-related and disease-related factors. Accordingly, the identification of a single biomarker of sarcopenia is unreliable, due to its "multifactorial" pathogenesis with the involvement of a multitude of pathways. Thus, in order to characterize pathophysiological mechanisms and to make a correct assessment of elderly patient with sarcopenia, a panel of biomarkers of all pathways involved should be assessed.

Permanent AF is characterized by an increased mortality in elderly subjects with CHF. Moreover, AF increased the risk of mortality also in elderly subjects without CHF. Thus, we examined long-term mortality in community-dwelling elderly people with and without CHF. A total of 1332 subjects aged 65 and older were selected from the electoral rolls of Campania, a region of southern Italy. The relationship between AF and mortality during a 12-year follow-up in 125 subjects with CHF and in 1.143 subjects without CHF were studied. Elderly subjects showed a higher mortality in those with respect to those without AF (72.1% vs. 51.8%; p< 0.01). Similarly, elderly subjects without CHF showed a higher mortality in those with respect to those without AF (61.8% vs. 49.8%; p< 0.05). In contrast, elderly subjects with CHF showed a similar mortality in those with respect to those without AF (74.7% vs. 82.4%; p=. 0.234). Multivariate analysis shows that AF was predictive of mortality in all elderly subjects (Hazard Risk = HR = 1.39, 95% confidence interval (CI) = 1.25-2.82; p< 0.001). When the analysis was conducted considering the presence and the absence of CHF, AF was strongly predictive of mortality in elderly subjects without CHF (HR = 1.95, 95%CI = 1.25-4.51; p< 0.001) but not in those with CHF (HR = 1.12, 95%CI = 0.97-3.69; p=. 0.321). We concluded that AF is able to predict long-term mortality in elderly subjects. Moreover, AF is strongly predictive of long-term mortality in the absence but not in the presence of CHF. © 2011 Elsevier Ireland Ltd.

Background Several studies suggest transient ischemic attack (TIA) may be neuroprotective against ischemic stroke analogous to preinfarction angina's protection against acute myocardial infarction. However, this protective ischemic preconditioning-like effect may not be present in all ages, especially among the elderly. The purpose of this study was to determine the neuroprotective effect of TIAs (clinical equivalent of cerebral ischemic preconditioning) to neurologic damage after cerebral ischemic injury in patients over 65 years of age. Methods We reviewed the medical charts of patients with ischemic stroke for presence of TIAs within 72 hours before stroke onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale and disability by a modified Rankin scale. Results We evaluated 203 patients (≥65 years) with diagnosis of acute ischemic stroke and categorized them according to the presence (n = 42, 21%) or absence (n = 161, 79%) of TIAs within 72 hours of stroke onset. Patients were monitored until discharged from the hospital (length of hospital stay 14.5 ± 4.8 days). No significant differences in the National Institutes of Health Stroke Scale and modified Rankin scale scores were observed between those patients with TIAs and those without TIAs present before stroke onset at admission or discharge. Conclusion These results suggest that the neuroprotective mechanism of cerebral ischemic preconditioning may not be present or functional in the elderly.

Mortality related to heart rate (HR) increase in the elderly has not yet been well established. To ascertain the relationships among cognitive impairment (CI), mortality, and HR increase, the authors prospectively studied a random sample of elderly subjects stratified according to presence or absence of CI. Elderly subjects randomly selected in 1991 (n = 1332) were followed up for 12 years. Mortality was established in 98.1% of the subjects. When HR was stratified in quartiles (69, 70-75, 76-80, and80 bpm), mortality was linearly associated with increased HR in all (from 47.7 to 57.0; r2 = .43, p = .019) and in subjects without (from 41.7 to 51.1%; r2 = .50, p = .043) but not in those with CI (from 57.5 to 66.1; r2 = .20, p = .363). Cox regression analysis, adjusted for several variables, shows that HR doesn't predict mortality in all subjects (RR 0.69; 95% CI = 0.27-1.73) or in those with CI (RR 0.91; 95% CI = 0.81-1.02). In contrast, HR predicts mortality in subjects without CI (RR 1.10; 95% CI = 1.00-1.22). Hence, HR increase is a predictor of mortality in elderly subjects without CI. However, when considering all elderly subjects and those with CI, HR increase seems to have no effect on mortality. Thus, CI should be considered when focusing on HR increase as risk factor for mortality in the elderly.

Objective: Moderate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF. Settings: community-dwelling from 5 regions of Italy. Participants: A cohort of 1332 subjects aged 65 and older. Measurement: Mortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers). Results: In the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66-0.95; p

Elderly subjects are characterized by a high prevalence of diabetes and clinical frailty. This study aimed to examine the predictive role of clinical frailty on long-term mortality in elderly subjects with and without diabetes. The study evaluated mortality after 12-year follow-up in 188 subjects with diabetes and 1,100 subjects without diabetes selected in 1992. Clinical frailty was assessed according to the “Frailty Staging System” and stratified in tertiles. After 12-year follow-up, mortality was 50.5 % in subjects without and 66.5 % in subjects with diabetes (p < 0.001). With increasing frailty, mortality increases from 57.9 to 79.0 % (p for trend

A subthreshold ischemic insult applied to an organ such as the heart and/or brain may help to reduce damage caused by subsequent ischemic episodes. This phenomenon is known as ischemic tolerance mediated by ischemic preconditioning (IPC) and represents the most powerful endogenous mechanism against ischemic injury. Various molecular pathways have been implicated in IPC, and several compounds have been proposed as activators or mediators of IPC. Recently, it has been established that the protective phenotype in response to ischemia depends on a coordinated response at the genomic, molecular, cellular and tissue levels by introducing the concept of ‘genomic reprogramming’ following IPC. In this article, we sought to review the genetic expression profiles found in cardiac and cerebral IPC studies, describe the differences between young and aged organs in IPC-mediated protection, and discuss the potential therapeutic application of IPC and pharmacological preconditioning based on the genomic response.

Background: The role of ventricular rate response (VRr) on the incidence of dementia in elderly subjects with cognitive impairment and atrial fibrillation (AF) is not known. Thus, we examined the ability of VRr to predict dementia in cognitively impaired elderly subjects with and without AF. Methods: A total of 358 cognitively impaired elderly subjects (MMSE 90) and moderate (>50/90 bpm) is predictive of dementia in the presence (HR = 7.70, 95% CI = 1.10–14.20, p = 0.03) but not in the absence (HR = 1.85; 95% CI = 0.78–4.47; p = 0.152) of AF. Conclusions: This study demonstrates that AF predicts dementia in elderly subjects with cognitive impairment. Moreover, VRr seems to play a key role in the incidence of dementia in cognitively impaired elderly subjects with AF.

Stroke remains a leading cause of death worldwide and the first cause of disability in the western world. Ischemic stroke (IS) accounts for almost 80% of the total cases of strokes and is a complex and multifactorial disease caused by the combination of vascular risk factors, environment and genetic factors. Investigations of the genetics of atherosclerosis and IS has greatly enhanced our knowledge of this complex multifactorial disease. In this article we sought to review common single-gene disorders relevant to IS, summarize candidate gene and genome-wide studies aimed at discovering genetic stroke risk factors and subclinical phenotypes, and to briefly discuss pharmacogenetics related to stroke treatments. Genetics of IS is, in fact, one of the most promising research frontiers and genetic testing may be helpful for novel drug discoveries as well as for appropriate drug and dose selection for treatment of patients with cerebrovascular disease.

Background and aims: Elderly subjects are characterized by a high prevalence of chronic obstructive pulmonary disease (COPD) and frailty. This study examined the predictive role of frailty on long-term mortality in elderly subjects with and without COPD. Methods: The study assessed mortality after a 12-year follow-up in 489 subjects with COPD and 799 subjects without COPD, selected in 1992. Frailty was assessed according to the Frailty Staging System scores ranging from 1 to 7. Results: After 12 years’ follow-up, mortality was 48.1% in subjects without and 60.7% in subjects with COPD (p

Cancer in elderly patients is an increasingly common problem. Older patients have more co-morbidity, therefore the toxic effects of chemotherapy treatment are less tolerable compared to younger patients. Platinum-based compounds (PBCs) are commonly used cytotoxic agents in the treatment of several solid tumors; however, their application is still limited in elderly patients, due to the risks in cardiovascular toxicity. The increased risk for myocardial ischemia, stroke, and vascular thrombosis linked with PBCs treatment is mainly due to reactive oxygen species (ROS) production and the subsequent induction of oxidative stress and switch to a prothrombotic condition. Recently, studies have shown a different genetic susceptibility in cardiovascular toxicity induced by therapy with PBCs. Antioxidants, such as vitamin E, selenium, lycopene, melatonin, and resveratrol, have been implicated in cancer treatment by their property to suppress the oxidant injury. Resveratrol, especially, has been shown to increase the antineoplastic activity of cisplatin. In addition, resveratrol's ability to activate the sirtuin1 (SIRT1) pathway has been heavily implicated in the mechanisms controlling longevity and quality of life in the aged population. This article reviews the current state of treatment with PBCs and their associated risk for cardiovascular disease. It discusses the most powerful antioxidant supplementation options as a possible strategy to reduce the cardiovascular toxicity effects of chemotherapy in the elderly.

Background Preinfarction angina (PrA), clinical equivalent of ischemic preconditioning, confers protection against inhospital mortality for acute myocardial infarction (AMI) in adult but not in elderly patients. This study aims to examine the interaction between physical activity and body mass index (BMI) in preserving the cardioprotective effect of PrA in elderly patients with AMI. Design Elderly patients (Z65 years old) with AMI admitted to Coronary Care Unit. Methods Elderly patients with AMI were retrospectively stratified for the presence and absence of PrA, and for quartiles of BMI and physical activity. In-hospital outcomes (death, cardiogenic shock, and reinfarction and creatine kinase-MB peak) were evaluated. Results In-hospital mortality of 1014 elderly patients with AMI was 19.2% in those with PrA and 22.7% in those without (P = 0.18, NS). Mortality further decreased with increased physical activity and reduced BMI, a trend that was not observed in patients without PrA. When physical activity and BMI were considered together, lowest in-hospital mortality was observed in patients with highest physical activity and normal BMI (from 18.2 to 9.6%; P < 0.01) with the greatest reduction observed in patients with PrA (from 18.3 to 5.1%; P =0.02). Multivariate analysis showed that PrA did not exert a protective effect in all patients irrespective of physical activity and BMI. A protective role was, however, observed in patients with highest physical activity or normal BMI and reached a maximum protective role in patients who showed both highest physical activity and normal BMI [odds ratio =0.08; 95% confidence interval = 0.02–0.72; P < 0.01]. Conclusion The cardioprotective effect of PrA was preserved in elderly patients who showed the highest physical activity and a normal BMI.

Background: comorbidity plays a critical role in the high mortality for chronic heart failure (CHF) in the elderly. Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index. No studies are available on the ability of CCI to predict mortality in CHF elderly subjects. The aim of the present study was to assess if CCI was able to predict long-term mortality in a random sample of elderly CHF subjects. Methods: long-term mortality after 12-year follow-up in 125 subjects with CHF and 1,143 subjects without CHF was studied. Comorbidity was evaluated using CCI. Findings: in elderly subjects stratified for CCI (1‐3 and ≥4), mortality was higher in non-CHF subjects with CCI ≥4 (52.4% versus 70%, P < 0.002) but not in those with CHF (75.9% versus 77.6%, P = 0.498, NS). Cox regression analysis on 12 years mortality indicated that both CCI (HR = 1.15; 95% CI = 1.01‐1.31; P = 0.035) and CHF (HR = 1.27; 95% CI = 1.04‐8.83; P = 0.003) were predictive of mortality. When Cox analysis was performed by selecting the presence and the absence of CHF, CCI was predictive of mortality in the absence but not in the presence of CHF. Conclusion: CCI does not predict long-term mortality in elderly subjects with CHF.

The life span of human beings is partially influenced by genetic factors, but outcomes of aging are profoundly influenced by lifestyle and other environmental factors. Age-related modifications of the cardiovascular system are preserved by antiaging lifestyle interventions such as physical activity and caloric restriction. Accordingly, physical activity and low body mass index reduce mortality in older men with cardiovascular diseases. Several mechanisms have been proposed to explain the protective effect of lifestyle interventions against cardiovascular diseases in the elderly, including a reduction of vulnerability (i.e., the age-related reduction of endogenous mechanisms protective against pathologic insults). The age-related reduction of ischemic preconditioning, the most powerful endogenous protective mechanism against myocardial ischemia, is restored by both physical activity and caloric restriction. Thus, older persons can implement lifestyle practices that minimize their risk of death from cardiovascular diseases.

Background The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study aimed to examine the predictive role of frailty on long-term mortality in elderly subjects with CHF. Materials and methods The study assessed long-term mortality after 12-year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a ‘Frailty Staging System’. Results Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75·9 ± 6·7); subjects without CHF were prevalently female (56·4%) and younger than 75 years (mean 74·0 ± 6·3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70·0% to 94·4%, P

Background The aging heart is characterized by structural changes, which are implicated in the development of left ventricular diastolic dysfunction. However, important changes in systolic function may also occur. Left ventricular end-systolic elastance (Ees) is a major determinant of cardiac systolic function and ventricular—arterial interaction. Aim To evaluate left-ventricular Ees in elderly subjects compared with adult control subjects. Methods We studied dilated (DA, n=14) and hypertensive (HA, n=21) cardiomyopathy patients, and both adult control (A, n=25; age 55.6±6.6 years) and elderly (E, n=25; age 76.3±7.1 years) subjects without clinical–instrumental evidence of cardiovascular disease. M-mode, two-dimensional, and pulsed Doppler echocardiogram were performed. Doppler-derived indices of diastolic function were assessed and Ees was calculated by a modified single-beat method. Results Ees was reduced in dilated cardiomyopathy (1.32±0.10 mm Hg/ml) and increased in hypertensive cardiomyopathy (3.12±0.33 mm Hg/ml) patients compared to age-matched control subjects (1.96±0.26 mm Hg/ml; p

A high falls-related mortality rate in the elderly is not exclusively related to injuries. Moreover, the risk of falls increases with urinary disorders such as nocturia. The aim of this study was to investigate the role of nocturia in falls-related long-term mortality in elderly subjects.Longitudinal study.The "Osservatorio Geriatrico Regione Campania" was a cross-sectional study performed in 1992 in Campania, a region of Southern Italy.Long-term mortality (12 years' follow-up) in 178 elderly subjects (mean age 74.0 ± 6.3 years) with falls and 1110 elderly subjects (mean age 75.2 ± 6.4 years) without falls at baseline was measured. Subjects were then stratified for the presence/absence of nocturia.In our sample, the prevalence of falls was 13.8% and the prevalence of nocturia was 45.7%. Long-term mortality was 51.3% in nonfallers and 62.9% in fallers (P.05). In the absence of nocturia, long-term mortality was similar in nonfallers and fallers (49.0% vs 46.7%; P = .514, NS). In contrast, in the presence of nocturia, long-term mortality was higher in fallers than in nonfallers (74.5% vs 53.6%; P.05). Cox regression analysis confirmed the predictive role of falls on long-term mortality in the presence of nocturia (hazard ratio 60; 95% confidence interval 1.01-2.57; P.05) but not in the absence of nocturia (hazard ratio = 1.27; 95% confidence interval 0.81-1.99; P = .28).Our data suggest that falls are related to an increased risk of long-term mortality in the elderly much more in the presence of nocturia. This phenomenon is probably related to the high comorbidity that usually affects elderly subjects with nocturia.

Senescence is a phenomenon characterized by a progressive decline of body homeostasis. Premature senescence acts when the cellular system is not able to adequately respond to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a state of accelerating aging. Moreover, SGK-1-sensitive ion channels participate in the regulation of renal Na(+)/K(+) regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently, we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia. Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases, and cardiovascular disease, among other age-related diseases. However, to date, the data available on SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target to counteract and prevent aging.