171 results on '"Robertina Giacconi"'
Search Results
2. Blood circulating bacterial DNA in hospitalized old COVID-19 patients
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Robertina Giacconi, Patrizia D’Aquila, Maurizio Cardelli, Francesco Piacenza, Elisa Pierpaoli, Giada Sena, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Massimiliano Fedecostante, Riccardo Sarzani, Chiara Di Pentima, Piero Giordano, Roberto Antonicelli, Fabrizia Lattanzio, Giuseppe Passarino, Mauro Provinciali, and Dina Bellizzi
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COVID-19 ,Hospitalization ,Circulating bacterial DNA ,Aging ,Inflammation ,Mortality ,Immunologic diseases. Allergy ,RC581-607 ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. Results BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65–99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. Conclusions The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.
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- 2023
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3. Spreading Senescent Cells’ Burden and Emerging Therapeutic Targets for Frailty
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Serena Marcozzi, Giorgia Bigossi, Maria Elisa Giuliani, Giovanni Lai, Robertina Giacconi, Francesco Piacenza, and Marco Malavolta
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aging ,frailty ,cellular senescence ,immunosenescence ,microbiome ,virome ,Cytology ,QH573-671 - Abstract
The spreading of senescent cells’ burden holds profound implications for frailty, prompting the exploration of novel therapeutic targets. In this perspective review, we delve into the intricate mechanisms underlying senescent cell spreading, its implications for frailty, and its therapeutic development. We have focused our attention on the emerging age-related biological factors, such as microbiome and virome alterations, elucidating their significant contribution to the loss of control over the accumulation rate of senescent cells, particularly affecting key frailty domains, the musculoskeletal system and cerebral functions. We believe that gaining an understanding of these mechanisms could not only aid in elucidating the involvement of cellular senescence in frailty but also offer diverse therapeutic possibilities, potentially advancing the future development of tailored interventions for these highly diverse patients.
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- 2023
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4. Plasma Bacterial DNA Load as a Potential Biomarker for the Early Detection of Colorectal Cancer: A Case–Control Study
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Robertina Giacconi, Rossella Donghia, Graziana Arborea, Maria Teresa Savino, Mauro Provinciali, Fabrizia Lattanzio, Giusy Rita Caponio, Sergio Coletta, Antonia Bianco, Maria Notarnicola, Caterina Bonfiglio, Giuseppe Passarino, Patrizia D’Aquila, Dina Bellizzi, and Pasqua Letizia Pesole
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colorectal cancer ,microbiota ,bacterial DNA ,Biology (General) ,QH301-705.5 - Abstract
The gut microbiota has gained increasing attention in recent years due to its significant impact on colorectal cancer (CRC) development and progression. The recent detection of bacterial DNA load in plasma holds promise as a potential non-invasive approach for early cancer detection. The aim of this study was to examine the quantity of bacterial DNA present in the plasma of 50 patients who have CRC in comparison to 40 neoplastic disease-free patients, as well as to determine if there is a correlation between the amount of plasma bacterial DNA and various clinical parameters. Plasma bacterial DNA levels were found to be elevated in the CRC group compared to the control group. As it emerged from the logistic analysis (adjusted for age and gender), these levels were strongly associated with the risk of CRC (OR = 1.02, p < 0.001, 95% C.I.: 1.01–1.03). Moreover, an association was identified between a reduction in tumor mass and the highest tertile of plasma bacterial DNA. Our findings indicate that individuals with CRC displayed a higher plasma bacterial DNA load compared to healthy controls. This observation lends support to the theory of heightened bacterial migration from the gastrointestinal tract to the bloodstream in CRC. Furthermore, our results establish a link between this phenomenon and the size of the tumor mass.
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- 2023
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5. Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38+ macrophages and NAD+ decline
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Elena Ciaglia, Valentina Lopardo, Francesco Montella, Albino Carrizzo, Paola Di Pietro, Marco Malavolta, Robertina Giacconi, Fiorenza Orlando, Monica Cattaneo, Paolo Madeddu, Carmine Vecchione, and Annibale Alessandro Puca
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Cytology ,QH573-671 - Abstract
Abstract As we age, our body experiences chronic, systemic inflammation contributing to the morbidity and mortality of the elderly. The senescent immune system has been described to have a causal role in driving systemic aging and therefore may represent a key therapeutic target to prevent pathological consequences associated with aging and extend a healthy lifespan. Previous studies from our group associated a polymorphic haplotype variant in the BPIFB4 gene (LAV-BPIFB4) with exceptional longevity. Transfer of the LAV-BPIFB4 in preclinical models halted the progression of cardiovascular diseases (CVDs) and frailty by counterbalancing chronic inflammation. In the present study, we aimed to delineate the action of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer (AAV-LAV-BPIFB4) on the deleterious age-related changes of the immune system and thereby the senescence-associated events occurring in C57BL/6J mice aged 26 months. Our in vivo data showed that 26-months-old mice had a higher frequency of CD45+SA-beta Gal+ immune cells in peripheral blood than young (4-months-old) C57BL/6J mice. Notably, AAV-LAV-BPIFB4 gene transfer in aged mice reduced the pool of peripheral immunosenescent cells that were shown to be enriched in the spleen. In addition, the proper tuning of the immune secretory phenotype (IL1βlow, IL6low, IL10high) associated with a significant reduction in SA-beta Gal-positive area of aorta from AAV-LAV treated mice. At the functional level, the reduction of senescence-associated inflammation ensured sustained NAD+ levels in the plasma of AAV-LAV-BPIFB4 old mice by preventing the NADase CD38 increase in F4/80+ tissue-resident macrophages and Ly6Chigh pro-inflammatory monocytes of the spleen and bone marrow. Finally, to validate the clinical implication of our findings, we showed that Long-living-individuals (LLIs, >95 years), which delay CVDs onset, especially if LAV-carriers, were characterized by high NAD+ levels. In conclusion, the new senotherapeutic action of LAV-BPIFB4 may offer a valuable therapeutic tool to control aging and reduce the burden of its pathophysiological disorders, such as CVDs.
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- 2022
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6. Uncovering the Relationship between Selenium Status, Age, Health, and Dietary Habits: Insights from a Large Population Study including Nonagenarian Offspring from the MARK-AGE Project
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Robertina Giacconi, Francesco Piacenza, Valentina Aversano, Michele Zampieri, Alexander Bürkle, María Moreno Villanueva, Martijn E. T. Dollé, Eugène Jansen, Tilman Grune, Efstathios S. Gonos, Claudio Franceschi, Miriam Capri, Birgit Weinberger, Ewa Sikora, Olivier Toussaint, Florence Debacq-Chainiaux, Wolfgang Stuetz, Pieternella Eline Slagboom, Jürgen Bernhardt, Maria Luisa Fernández-Sánchez, Mauro Provinciali, and Marco Malavolta
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selenium fractionation ,plasma selenium ,longevity ,aging ,inflammation ,Nutrition. Foods and food supply ,TX341-641 - Abstract
An inadequate selenium (Se) status can accelerate the aging process, increasing the vulnerability to age-related diseases. The study aimed to investigate plasma Se and Se species in a large population, including 2200 older adults from the general population (RASIG), 514 nonagenarian offspring (GO), and 293 GO Spouses (SGO). Plasma Se levels in women exhibit an inverted U-shaped pattern, increasing with age until the post-menopausal period and then declining. Conversely, men exhibit a linear decline in plasma Se levels with age. Subjects from Finland had the highest plasma Se values, while those from Poland had the lowest ones. Plasma Se was influenced by fish and vitamin consumption, but there were no significant differences between RASIG, GO, and SGO. Plasma Se was positively associated with albumin, HDL, total cholesterol, fibrinogen, and triglycerides and negatively associated with homocysteine. Fractionation analysis showed that Se distribution among plasma selenoproteins is affected by age, glucometabolic and inflammatory factors, and being GO or SGO. These findings show that sex-specific, nutritional, and inflammatory factors play a crucial role in the regulation of Se plasma levels throughout the aging process and that the shared environment of GO and SGO plays a role in their distinctive Se fractionation.
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- 2023
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7. Preliminary Comparison of Fractional Absorption of Zinc Sulphate, Zinc Gluconate, and Zinc Aspartate after Oral Supple-Mentation in Healthy Human Volunteers
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Francesco Piacenza, Robertina Giacconi, Laura Costarelli, and Marco Malavolta
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zinc ,absorption ,stable isotopes ,zinc-aspartate ,zinc-gluconate ,zinc sulphate ,Nutrition. Foods and food supply ,TX341-641 - Abstract
(1) Background: Zinc is generally used as a nutritional supplement for individuals at nutritional risk, such as older adults. This preliminary study investigated the fractional Zn absorption (FZA) after the supplementation on eight healthy volunteers with three different Zn complexes acquired with milk. (2) Methods: The design was a double-blind, three-period crossover trial. The volunteers were randomly divided into three groups. Each individual consumed 200 mL of bovine milk and rotated through a simultaneous administration of a single oral dose of 70ZnSO4, 70Zn-Gluconate (70Zn-Glu), and 70Zn-Aspartate (70Zn-Asp), equivalent to 2.0 mg 70Zn, followed by 2 weeks of wash-out. An estimation of the FZA for comparative purposes was computed by the isotopic ratio between 66Zn and 70Zn in urine collected before and 48 h after administration. (3) Results: The estimated FZA was found to be significantly higher for 70Zn-Asp when compared to the other forms, while the FZA of 70Zn-Glu was found to be significantly higher than 70ZnSO4. (4) Conclusions: The results of this study suggest that complexing Zn with aspartate in milk could be a useful tool to improve FZA in individuals at risk of Zn deficiency. These results provide a rationale for conducting further studies on Zn-Asp preparations.
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- 2023
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8. Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients
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Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Elisa Pierpaoli, Elisabetta Farnocchia, MirKo Di Rosa, Anna Rita Bonfigli, Tiziana Casoli, Francesca Marchegiani, Fiorella Marcheselli, Rina Recchioni, Pierpaolo Stripoli, Roberta Galeazzi, Antonio Cherubini, Massimiliano Fedecostante, Riccardo Sarzani, Chiara Di Pentima, Piero Giordano, Roberto Antonicelli, Mauro Provinciali, and Fabrizia Lattanzio
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COVID-19 patients ,cytomegalovirus ,aging ,inflammation ,mortality ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66–59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05–1.30), neutrophil count (HR: 1.20, 95% CI: 1.01–1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04–2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05–1.21) and age (HR: 1.15, 95% CI: 1.01–1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.
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- 2023
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9. Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice
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Maria Elisa Giuliani, Veronica Barbi, Giorgia Bigossi, Serena Marcozzi, Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Fiorenza Orlando, Elena Ciaglia, Monica Cattaneo, Alessia Mongelli, Carlo Gaetano, Mauro Provinciali, Annibale Alessandro Puca, and Marco Malavolta
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aging ,epigenetic clock ,frailty ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging. In this study, we show that the systemic gene transfer of LAV-BPIFB4 in aged C57BL/6J mice was associated with a significant reduction in the epigenetic clock-based biological age, as measured by a three CpG clock method. Furthermore, LAV-BPIFB4 gene transfer resulted in an improvement of the Vitality Score with a reduction in the Frailty Index. These findings further support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in aged mice, with potential implications for future therapies to prevent frailty in humans.
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- 2023
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10. Sensibility and Specificity of the VitaPCR™ SARS-CoV-2 Assay for the Rapid Diagnosis of COVID-19 in Older Adults in the Emergency Department
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Francesco Piacenza, Antonio Cherubini, Roberta Galeazzi, Maurizio Cardelli, Robertina Giacconi, Elisa Pierpaoli, Francesca Marchegiani, Fiorella Marcheselli, Rina Recchioni, Tiziana Casoli, Elisabetta Farnocchia, Beatrice Bartozzi, Belinda Giorgetti, Pierpaolo Stripoli, Anna Rita Bonfigli, Massimiliano Fedecostante, Fabio Salvi, Adolfo Pansoni, Mauro Provinciali, and Fabrizia Lattanzio
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sensitivity ,specificity ,rapid diagnostic test ,VitaPCR ,SARS-CoV-2 ,Microbiology ,QR1-502 - Abstract
(1) Background: During the COVID-19 pandemic, rapid and reliable diagnostic tools are needed for detecting SARS-CoV-2 infection in urgent cases at admission to the hospital. We aimed to assess the performances of the rapid molecular VitaPCR™ test (Menarini Diagnostics) in a sample of older adults admitted to the Emergency Department of two Italian hospitals (2) Methods: The comparison between the rapid VitaPCR™ and the RT-PCR was performed in 1695 samples. Two naso-pharyngeal swab samplings from each individual were obtained and processed using the VitaPCR™ and the RT-PCR for the detection of SARS-CoV-2 (3) Results: VitaPCR™ exhibited good precision (
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- 2023
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11. Bacterial DNAemia in Alzheimer’s Disease and Mild Cognitive Impairment: Association with Cognitive Decline, Plasma BDNF Levels, and Inflammatory Response
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Robertina Giacconi, Patrizia D’Aquila, Marta Balietti, Cinzia Giuli, Marco Malavolta, Francesco Piacenza, Laura Costarelli, Demetrio Postacchini, Giuseppe Passarino, Dina Bellizzi, and Mauro Provinciali
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circulating bacterial DNA ,inflammation ,BDNF ,Alzheimer’s disease ,mild cognitive impairment ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Microbial dysbiosis (MD) provokes gut barrier alterations and bacterial translocation in the bloodstream. The increased blood bacterial DNA (BB-DNA) may promote peripheral- and neuro-inflammation, contributing to cognitive impairment. MD also influences brain-derived neurotrophic factor (BDNF) production, whose alterations contribute to the etiopathogenesis of Alzheimer’s disease (AD). The purpose of this study is to measure BB-DNA in healthy elderly controls (EC), and in patients with mild cognitive impairment (MCI) and AD to explore the effect on plasma BDNF levels (pBDNF), the inflammatory response, and the association with cognitive decline during a two-year follow-up. Baseline BB-DNA and pBDNF were significantly higher in MCI and AD than in EC. BB-DNA was positively correlated with pBDNF in AD, plasma Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) levels in MCI. AD patients with BB-DNA values above the 50th percentile had lower baseline Mini-Mental State Examination (MMSE). After a two-year follow-up, AD patients with the highest BB-DNA tertile had a worse cognitive decline, while higher BB-DNA levels were associated with higher TNF-α and lower IL-10 in MCI. Our study demonstrates that, in early AD, the higher the BB-DNA levels, the higher the pBDNF levels, suggesting a defensive attempt; BB-DNA seems to play a role in the AD severity/progression; in MCI, higher BB-DNA may trigger an increased inflammatory response.
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- 2022
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12. Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry
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Marco Malavolta, Robertina Giacconi, Francesco Piacenza, Sergio Strizzi, Maurizio Cardelli, Giorgia Bigossi, Serena Marcozzi, Luca Tiano, Fabio Marcheggiani, Giulia Matacchione, Angelica Giuliani, Fabiola Olivieri, Ilaria Crivellari, Antonio Paolo Beltrami, Alessandro Serra, Marco Demaria, and Mauro Provinciali
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cellular senescence ,imaging flow cytometry ,senolytics ,replicative senescence ,artificial intelligence and machine learning ,Cytology ,QH573-671 - Abstract
Cellular senescence is a hallmark of aging and a promising target for therapeutic approaches. The identification of senescent cells requires multiple biomarkers and complex experimental procedures, resulting in increased variability and reduced sensitivity. Here, we propose a simple and broadly applicable imaging flow cytometry (IFC) method. This method is based on measuring autofluorescence and morphological parameters and on applying recent artificial intelligence (AI) and machine learning (ML) tools. We show that the results of this method are superior to those obtained measuring the classical senescence marker, senescence-associated beta-galactosidase (SA-β-Gal). We provide evidence that this method has the potential for diagnostic or prognostic applications as it was able to detect senescence in cardiac pericytes isolated from the hearts of patients affected by end-stage heart failure. We additionally demonstrate that it can be used to quantify senescence “in vivo” and can be used to evaluate the effects of senolytic compounds. We conclude that this method can be used as a simple and fast senescence assay independently of the origin of the cells and the procedure to induce senescence.
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- 2022
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13. Microbiome in Blood Samples From the General Population Recruited in the MARK-AGE Project: A Pilot Study
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Patrizia D’Aquila, Robertina Giacconi, Marco Malavolta, Francesco Piacenza, Alexander Bürkle, María Moreno Villanueva, Martijn E. T. Dollé, Eugène Jansen, Tilman Grune, Efstathios S. Gonos, Claudio Franceschi, Miriam Capri, Beatrix Grubeck-Loebenstein, Ewa Sikora, Olivier Toussaint, Florence Debacq-Chainiaux, Antti Hervonen, Mikko Hurme, P. Eline Slagboom, Christiane Schön, Jürgen Bernhardt, Nicolle Breusing, Giuseppe Passarino, Mauro Provinciali, and Dina Bellizzi
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blood microbiome ,16S rRNA gene ,geographic origin ,aging ,free fatty acids ,leukocytes ,Microbiology ,QR1-502 - Abstract
The presence of circulating microbiome in blood has been reported in both physiological and pathological conditions, although its origins, identities and function remain to be elucidated. This study aimed to investigate the presence of blood microbiome by quantitative real-time PCRs targeting the 16S rRNA gene. To our knowledge, this is the first study in which the circulating microbiome has been analyzed in such a large sample of individuals since the study was carried out on 1285 Randomly recruited Age-Stratified Individuals from the General population (RASIG). The samples came from several different European countries recruited within the EU Project MARK-AGE in which a series of clinical biochemical parameters were determined. The results obtained reveal an association between microbial DNA copy number and geographic origin. By contrast, no gender and age-related difference emerged, thus demonstrating the role of the environment in influencing the above levels independent of age and gender at least until the age of 75. In addition, a significant positive association was found with Free Fatty Acids (FFA) levels, leukocyte count, insulin, and glucose levels. Since these factors play an essential role in both health and disease conditions, their association with the extent of the blood microbiome leads us to consider the blood microbiome as a potential biomarker of human health.
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- 2021
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14. Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats
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Marco Malavolta, Robertina Giacconi, Dario Brunetti, Mauro Provinciali, and Fabrizio Maggi
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cellular senescence ,viral infection ,inflammation ,mitochondria ,extracellular vesicles ,senoptotics ,Cytology ,QH573-671 - Abstract
The higher death rate caused by COVID-19 in older people, especially those with comorbidities, is a challenge for biomedical aging research. Here we explore the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, may drive the deleterious consequences of the infection. Data shows that other RNA viruses, such as influenza virus, can display enhanced replication efficiency in senescent cells, suggesting that the accumulation of senescent cells with aging and age-related diseases may play a role in this phenomenon. However, at present, we are completely unaware of the response to SARS-CoV and SARS-COV-2 occurring in senescent cells. We deem that this is a priority area of research because it could lead to the development of several therapeutic strategies based on senotherapeutics or prevent unsuccessful attempts. Two of these senotherapeutics, azithromycin and ruxolitinib, are currently undergoing testing for their efficacy in treating COVID-19. The potential of these strategies is not only for ameliorating the consequences of the current emergence of SARS-CoV-2, but also for the future emergence of new viruses or mutated ones for which we are completely unprepared and for which no vaccines are available.
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- 2020
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15. Targeting Oxidative Stress in Diabetic Complications: New Insights
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Hao Wu, Lu Cai, Judy B. de Haan, and Robertina Giacconi
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Published
- 2018
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16. Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy
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Marco Malavolta, Massimo Bracci, Lory Santarelli, Md Abu Sayeed, Elisa Pierpaoli, Robertina Giacconi, Laura Costarelli, Francesco Piacenza, Andrea Basso, Maurizio Cardelli, and Mauro Provinciali
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Pathology ,RB1-214 - Abstract
The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms) that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity.
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- 2018
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17. FKBP5 rs4713916: A Potential Genetic Predictor of Interindividual Different Response to Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease in a Real-Life Setting
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Patrizia Russo, Carlo Tomino, Alessia Santoro, Giulia Prinzi, Stefania Proietti, Aliaksei Kisialiou, Vittorio Cardaci, Massimo Fini, Mauro Magnani, Francesco Collacchi, Mauro Provinciali, Robertina Giacconi, Stefano Bonassi, and Marco Malavolta
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COPD ,inhaled corticosteroid ,lung function ,rehabilomics ,rs37972 ,rs471396 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient’s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.
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- 2019
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18. Cellular Senescence and Inflammatory Burden as Determinants of Mortality in Elderly People Until the Extreme old age
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Robertina Giacconi, Marco Malavolta, Laura Costarelli, and Mauro Provinciali
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Senescence ,Telomere ,Mortality ,Aging ,Longevity ,Medicine ,Medicine (General) ,R5-920 - Published
- 2015
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19. MetaTropismDB: a database of organ-specific metastasis induced by human cancer cell lines in mouse models.
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Matteo Giulietti, Marco Bastianoni, Monia Cecati, Annamaria Ruzzo, Massimo Bracci, Marco Malavolta, Francesco Piacenza, Robertina Giacconi, and Francesco Piva
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- 2020
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20. Platelet Total PLA2 Activity, Serum Oxidative Level, and Plasma Cu/Zn Ratio: A Vicious Cycle with a Potential Role to Monitor MCI and Alzheimer's Disease Progression
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Marta Balietti, Tiziana Casoli, Robertina Giacconi, and Cinzia Giuli
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Aging ,Geriatrics and Gerontology - Published
- 2022
21. Comprehensive longitudinal non-invasive quantification of healthspan and frailty in a large cohort (n = 546) of geriatric C57BL/6 J mice
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Serena Marcozzi, Giorgia Bigossi, Maria Elisa Giuliani, Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Fiorenza Orlando, Agnese Segala, Alessandra Valerio, Enzo Nisoli, Dario Brunetti, Annibale Puca, Federico Boschi, Carlo Gaetano, Alessia Mongelli, Fabrizia Lattanzio, Mauro Provinciali, and Marco Malavolta
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Aging ,Biomarkers of aging ,Epigenetic clock ,Biogerontology ,Geriatrics and Gerontology ,Cellular senescence ,Physical performance - Published
- 2023
22. Association of Torquetenovirus viremia with physical frailty and cognitive impairment in three independent European cohorts
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Robertina Giacconi, Blanca Laffon, Solange Costa, Armanda Teixeira-Gomes, Fabrizio Maggi, Lisa Macera, Pietro Giorgio Spezia, Francesco Piacenza, Alexander Bürkle, Maria Moreno-Villanueva, Stefano Bonassi, Vanessa Valdiglesias, João Paulo Teixeira, Martijn E.T. Dollé, M. Liset Rietman, Eugène Jansen, Tilman Grune, Efstathios S. Gonos, Claudio Franceschi, Miriam Capri, Birgit Weinberger, Ewa Sikora, Wolfgang Stuetz, Olivier Toussaint, Florence Debacq-Chainiaux, Antti Hervonen, Mikko Hurme, P. Eline Slagboom, Christiane Schön, Juergen Bernhardt, Nicolle Breusing, Eduardo Pásaro, Ana Maseda, Laura Lorenzo-López, José C. Millán-Calenti, Mauro Provinciali, and Marco Malavolta
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Inflammation ,Aging ,Cognitive impairment ,Torquetenovirus ,Geriatrics and Gerontology ,Physical frailty - Abstract
[Abstract] Introduction: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. Methods: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). Results: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06-10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14-5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000-1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. Conclusions: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals. Ministerio de Ciencia e Innovación (España); PID2020-113788RB-I00 Xunta de Galicia; ED431B 2022/16 Xunta de Galicia; ED431F 2017/09
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- 2022
23. Bacterial DNAemia in older participants and nonagenarian offspring and association with redox biomarkers
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Robertina Giacconi, Patrizia D’Aquila, Marco Malavolta, Francesco Piacenza, Alexander Bürkle, María Moreno Villanueva, Martijn E T Dollé, Eugène Jansen, Tilman Grune, Efstathios S Gonos, Claudio Franceschi, Miriam Capri, Daniela Gradinaru, Beatrix Grubeck-Loebenstein, Ewa Sikora, Wolfgang Stuetz, Daniela Weber, Olivier Toussaint, Florence Debacq-Chainiaux, Antti Hervonen, Mikko Hurme, P Eline Slagboom, Christiane Schön, Jürgen Bernhardt, Nicolle Breusing, Talbot Duncan, Giuseppe Passarino, Dina Bellizzi, Mauro Provinciali, Tampere University, BioMediTech, Giacconi R., D'Aquila P., Malavolta M., Piacenza F., Burkle A., Villanueva M.M., Dolle M.E.T., Jansen E., Grune T., Gonos E.S., Franceschi C., Capri M., Gradinaru D., Grubeck-Loebenstein B., Sikora E., Stuetz W., Weber D., Toussaint O., Debacq-Chainiaux F., Hervonen A., Hurme M., Slagboom P.E., Schon C., Bernhardt J., Breusing N., Duncan T., Passarino G., Bellizzi D., and Provinciali M.
- Subjects
Inflammation ,Aging ,Blood bacterial DNA ,Longevity ,Dysbiosis ,3111 Biomedicine ,Geriatrics and Gerontology ,Dysbiosi - Abstract
Aging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be further aggravated by antioxidant nutrient deficiency. Low plasma carotenoids are associated with an increased risk of inflammation and cellular damage and predict mortality. However, no evidence is yet available on the relationship between antioxidants and the blood bacterial DNA (BB-DNA). Therefore, this study aimed to compare BB-DNA from (a) GO (nonagenarian offspring), (b) age-matched controls (Randomly recruited Age-Stratified Individuals from the General population [RASIG]), and (c) spouses of GO (SGO) recruited in the MARK-AGE project, as well as to investigate the association between BB-DNA, behavior habits, Charlson Comorbidity Index (CCI), leucocyte subsets, and the circulating levels of some antioxidants and oxidative stress markers. BB-DNA was higher in RASIG than GO and SGO, whereas GO and SGO participants showed similar values. BB-DNA increased in smokers and males with CCI ≥ 2 compared with those with CCI ≤ 1 within RASIG. Moreover, BB-DNA was positively associated with lymphocyte, neutrophil, and monocyte counts, but not with self-reported dietary habits. Higher quartiles of BB-DNA were associated with low lutein and zeaxanthin and elevated malondialdehyde plasma concentrations in RASIG. BB-DNA was also positively correlated with nitric oxide levels. Herein, we provide evidence of a reduced BB-DNA in individuals from long-living families and their spouses, suggesting a decreased microbial dysbiosis and bacterial systemic translocation. BB-DNA was also associated with smoking, CCI, leukocyte subsets, and some redox biomarkers in older participants.
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- 2022
24. A New Robust Epigenetic Model for Forensic Age Prediction
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Robertina Giacconi, Dina Bellizzi, Alberto Montesanto, Ersilia Paparazzo, Mauro Provinciali, Patrizia D'Aquila, Maurizio Cardelli, Laura Formentini, Vincenzo Lagani, Silvana Geracitano, and Giuseppe Passarino
- Subjects
Adult ,Forensic Genetics ,Genetic Markers ,Male ,Aging ,Fatty Acid Elongases ,Computer science ,Age prediction ,LIM-Homeodomain Proteins ,Muscle Proteins ,Sample (statistics) ,Machine learning ,computer.software_genre ,Polymerase Chain Reaction ,Epigenesis, Genetic ,Pathology and Forensic Medicine ,Machine Learning ,Tripartite Motif Proteins ,Young Adult ,Forensic dna ,Genetics ,Humans ,Epigenetics ,Set (psychology) ,Aged ,Aged, 80 and over ,business.industry ,Intracellular Signaling Peptides and Proteins ,High-Throughput Nucleotide Sequencing ,DNA Methylation ,Middle Aged ,Italian population ,Biological materials ,Forensic science ,Linear Models ,CpG Islands ,Female ,Artificial intelligence ,business ,computer ,Transcription Factors - Abstract
Forensic DNA phenotyping refers to an emerging field of forensic sciences aimed at the prediction of externally visible characteristics of unknown sample donors directly from biological materials. The aging process significantly affects most of the above characteristics making the development of a reliable method of age prediction very important. Today, the so-called "epigenetic clocks" represent the most accurate models for age prediction. Since they are technically not achievable in a typical forensic laboratory, forensic DNA technology has triggered efforts toward the simplification of these models. The present study aimed to build an epigenetic clock using a set of methylation markers of five different genes in a sample of the Italian population of different ages covering the whole span of adult life. In a sample of 330 subjects, 42 selected markers were analyzed with a machine learning approach for building a prediction model for age prediction. A ridge linear regression model including eight of the proposed markers was identified as the best performing model across a plethora of candidates. This model was tested on an independent sample of 83 subjects providing a median error of 4.5 years. In the present study, an epigenetic model for age prediction was validated in a sample of the Italian population. However, its applicability to advanced ages still represents the main limitation in forensic caseworks.
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- 2020
25. Psycho-cognitive assessment and quality of life in older adults with chronic obstructive pulmonary disease-carrying the rs4713916 gene polymorphism (G/A) of gene FKBP5 and response to pulmonary rehabilitation. A proof of concept study
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Federica Marcolongo, Simone Scarlata, Carlo Tomino, Chiara De Dominicis, Robertina Giacconi, Marco Malavolta, Stefano Bonassi, Patrizia Russo, and Giulia Prinzi
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rehabilomics ,anxiety ,coping strategies ,depression ,pilot study ,Pilot Projects ,Polymorphism, Single Nucleotide ,Proof of Concept Study ,Tacrolimus Binding Proteins ,Psychiatry and Mental health ,Pulmonary Disease, Chronic Obstructive ,Cognition ,Genetics ,Quality of Life ,Humans ,Biological Psychiatry ,Genetics (clinical) ,Aged - Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extra-pulmonary multi-morbidity including depression, anxiety and cognitive disorders. Several studies investigated the association of the FKBP5 gene polymorphisms with susceptibility to anxiety, depression, and behavioral disorders. The FKBP5 gene codifies the FKBP51 protein which modulates the glucocorticoid receptor in the adaptive stress response. Genetic variants of the FKBP5 gene have been associated to a higher risk of developing mental disorders. We analyzed the association of genetic variants and stress exposure investigating the susceptibility to psychological distress and the impact on cognitive balance and quality of life (QoL) of COPD patients carrying the rs4713916 polymorphism (G/A) and we examined its association, with COPD rehabilitative outcomes.A pilot study evaluated cognitive, psychological, clinical alterations/disorders, QoL, and coping strategies in 70 older adults with COPD, undergoing pulmonary rehabilitation, stratified according to the FKBP5 rs4713916 genotype (GG or GA).Carriers of rs4713916 polymorphisms (G/A) show better cognitive performances, a higher degree of independence in the daily living activities, better QoL, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorders, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant, anti-psychotic, hypnotic-sedative drugs. No difference was found in the number of comorbidities.These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical, psychological and behavioral features of COPD patients.
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- 2022
26. Platelet Total PLA
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Marta, Balietti, Tiziana, Casoli, Robertina, Giacconi, and Cinzia, Giuli
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Oxidative Stress ,Phospholipases A2 ,Zinc ,Alzheimer Disease ,Disease Progression ,Humans ,Cognitive Dysfunction ,Biomarkers ,Copper ,Aged - Abstract
Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A
- Published
- 2021
27. Recovery from mild Escherichia coli O157:H7 infection in young and aged C57BL/6 mice with intact flora estimated by fecal shedding, locomotor activity and grip strength
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Fiorenza Orlando, Marco Malavolta, Maurizio Cardelli, Khadija Benlhassan, Serena Chierichetti, Francesca Leoni, Andrea Basso, Mauro Provinciali, Dorothy Bray, Elisa Pierpaoli, and Robertina Giacconi
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C57BL/6 ,Aging ,Flora ,medicine.drug_class ,Movement ,Immunology ,Antibiotics ,Physiology ,Oxytetracycline ,Escherichia coli O157 ,medicine.disease_cause ,Microbiology ,Foodborne Diseases ,Feces ,Mice ,Grip strength ,medicine ,Animals ,Immunology and Allergy ,Longitudinal Studies ,Pathogen ,Escherichia coli ,Escherichia coli Infections ,Hand Strength ,General Veterinary ,biology ,General Medicine ,biology.organism_classification ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Disease Models, Animal ,Infectious Diseases ,medicine.drug - Abstract
Escherichia coli 0157:H7 is a food-borne pathogen that can cause severe complications in vulnerable populations. Mouse infection models of E. coli 0157:H7 are usually developed under severe animal suffering classification by depleting the normal flora, in which age plays a role. Objective To develop a refined method for longitudinal monitoring of E. coli 0157:H7 in young and old mice with intact flora. Methods We applied discriminant analysis and computed composite standardized scores from 19 variables obtained from physiological parameters, analysis of locomotor activity, grip strength measurement and fecal shedding in 16 aged and 16 young C57BL/6 mice after two mild oral challenges of E. coli 0157:H7. The resulting scores were validated in another experiment performed in 24 aged and 24 young mice including a group (8 aged and 8 young mice) treated with oxytetracycline. Results We show that our scores are significantly affected in the post-infection period and that can be used to measure and compare the recovery time after a treatment. The scores are most sensitive when separately developed in young and aged mice. Conclusions We developed a method that minimizes the level of animal suffering and that can be applied in preclinical testing of new therapies.
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- 2019
28. Zinc supplementation can reduce accumulation of cadmium in aged metallothionein transgenic mice
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Robertina Giacconi, Kamil Pabis, Francesco Piacenza, Andrea Basso, Marco Malavolta, Mauro Provinciali, Claudia Gundacker, L. Costarelli, and Sergio Strizzi
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Male ,0301 basic medicine ,Genetically modified mouse ,medicine.medical_specialty ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,chemistry.chemical_element ,Mice, Transgenic ,Zinc ,010501 environmental sciences ,01 natural sciences ,Mice ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,Environmental Chemistry ,Metallothionein ,Binding site ,Aged ,0105 earth and related environmental sciences ,Cadmium ,Kidney ,Public Health, Environmental and Occupational Health ,General Medicine ,General Chemistry ,Metabolism ,Cd toxicity ,Pollution ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry - Abstract
Epidemiologic studies suggest that exposure to Cd is related to a multitude of age-related diseases. There is evidence that Cd toxicity emerges from an interference with Zn metabolism as they compete for the same binding sites of ligands. The most responsive proteins to Cd exposure are the metal-binding proteins termed metallothioneins (MTs), which display a much greater affinity for Cd than for Zn. Most studies have considered the effect of Zn on the accumulation of exogenous Cd and tissue damage, whereas observational studies have addressed the association between Zn intake and Cd levels in body fluids. However, it has not been addressed whether supplemental Zn can lower Cd levels in organs of healthy aged animals without affecting Cu stores, a question more pertinent to human aging. We therefore aimed to investigate the effect of Zn supplementation on Cd levels in liver and kidney of aged MT transgenic mice (MT1-tg) overexpressing MT1 at levels more comparable to those observed in humans than non-transgenic mice. We found a >30% reduction of kidney and liver Cd levels in Zn supplemented MT1-tg mice compared to non-supplemented controls, independently of the dose of Zn, without a significant reduction of Cu. Our data support the idea of a causal and inverse relationship between Zn intake and Cd content in organs of aged MT1-tg mice as suggested by observational studies in humans. Our work provides the rationale for interventional studies to address the effects of Zn supplementation on Cd burden in elderly people.
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- 2018
29. Age, Sex, and BMI Influence on Copper, Zinc, and Their Major Serum Carrier Proteins in a Large European Population including Nonagenarian Offspring from MARK-AGE Study
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Antti Hervonen, Martijn E.T. Dollé, Alexander Bürkle, Nicolle Breusing, Claudio Franceschi, Robertina Giacconi, Laura Costarelli, Maria Moreno-Villanueva, Mikko Hurme, Eline Slagboom, Daniela Weber, Marco Malavolta, Jürgen Bernhardt, Florence Debacq-Chainiaux, Efstathios S. Gonos, Wolfgang Stuetz, Olivier Toussaint, Andrea Basso, Tilman Grune, Francesco Piacenza, Eugenio Mocchegiani, Ewa Sikora, Miriam Capri, Beatrix Grubeck-Loebenstein, Eugène H.J.M. Jansen, Christiane Schön, Piacenza F., Giacconi R., Costarelli L., Basso A., Burkle A., Moreno-Villanueva M., Dolle M.E.T., Jansen E., Grune T., Weber D., Stuetz W., Gonos E.S., Schon C., Bernhardt J., Grubeck-Loebenstein B., Sikora E., Toussaint O., Debacq-Chainiaux F., Franceschi C., Capri M., Hervonen A., Hurme M., Slagboom E., Breusing N., Mocchegiani E., and Malavolta M.
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0301 basic medicine ,Male ,Aging ,medicine.medical_specialty ,Chronic inflammatory status ,Offspring ,Population ,chemistry.chemical_element ,Zinc ,Chronic inflammatory statu ,Body Mass Index ,Metallostasis ,03 medical and health sciences ,0302 clinical medicine ,Sex Factors ,Internal medicine ,Genetic model ,Homeostasi ,Homeostasis ,Medicine ,Humans ,education ,Aged ,education.field_of_study ,biology ,business.industry ,Albumin ,Age Factors ,Ceruloplasmin ,Copper ,030104 developmental biology ,Endocrinology ,Cross-Sectional Studies ,chemistry ,Nonagenarians ,biology.protein ,Female ,Geriatrics and Gerontology ,business ,Carrier Proteins ,Body mass index ,030217 neurology & neurosurgery ,Biomarkers - Abstract
The analysis of copper (Cu) and zinc (Zn) along with their major serum carriers, albumin (Alb) and ceruloplasmin (Cp), could provide information on the capacity of humans to maintain homeostasis of metals (metallostasis). However, their relationship with aging, sex, body mass index, as well as with nutritional and inflammatory markers was never investigated in a large-scale study. Here, we report results from the European large-scale cross-sectional study MARK-AGE in which Cu, Zn, Alb, Cp, as well as nutritional and inflammatory parameters were determined in 2424 age-stratified participants (35–75 years), including the general population (RASIG), nonagenarian offspring (GO), a well-studied genetic model of longevity, and spouses of GO (SGO). In RASIG, Cu to Zn ratio and Cp to Alb ratio were higher in women than in men. Both ratios increased with aging because Cu and Cp increased and Alb and Zn decreased. Cu, Zn, Alb, and Cp were found associated with several inflammatory as well as nutritional biomarkers. GO showed higher Zn levels and higher Zn to Alb ratio compared to RASIG, but we did not observe significant differences with SGO, likely as a consequence of the low sample size of SGO and the shared environment. Our results show that aging, sex, body mass index, and GO status are characterized by different levels of Cu, Zn, and their serum carrier proteins. These data and their relationship with inflammatory biomarkers support the concept that loss of metallostasis is a characteristic of inflammaging.
- Published
- 2021
30. Elevated metallothionein expression in long-lived species mediates the influence of cadmium accumulation on aging
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Paolo Garagnani, Marco Malavolta, Claudia Sala, Mauro Provinciali, Kamil Pabis, Robertina Giacconi, Elisabeth Straka, Ylenia Chiari, Xinna Li, Holly M. Brown-Borg, Teresa G. Valencak, Claudia Gundacker, Karin Nowikovsky, Pabis K., Chiari Y., Sala C., Straka E., Giacconi R., Provinciali M., Li X., Brown-Borg H., Nowikovsky K., Valencak T.G., Gundacker C., Garagnani P., and Malavolta M.
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Aging ,media_common.quotation_subject ,Longevity ,chemistry.chemical_element ,Biology ,Kidney ,Mammal ,Mice ,Gene expression ,Metallothionein ,Animals ,Gene ,Maximum life span ,media_common ,Cadmium ,Animal ,Molecular medicine ,Comparative biogerontology ,Cell biology ,chemistry ,Liver ,Original Article ,Geriatrics and Gerontology ,Homeostasis - Abstract
Cadmium (Cd) accumulates with aging and is elevated in long-lived species. Metallothioneins (MTs), small cysteine-rich proteins involved in metal homeostasis and Cd detoxification, are known to be related to longevity. However, the relationship between Cd accumulation, the role of MTs, and aging is currently unclear. Specifically, we do not know if long-lived species evolved an efficient metal stress response by upregulating their MT levels to reduce the toxic effects of environmental pollutants, such as Cd, that accumulate over their longer life span. It is also unknown if the number of MT genes, their expression, or both protect the organisms from potentially damaging effects during aging. To address these questions, we reanalyzed several cross-species studies and obtained data on MT expression and Cd accumulation in long-lived mouse models. We confirmed a relationship between species maximum life span in captive mammals and their Cd content in liver and kidney. We found that although the number of MT genes does not affect longevity, gene expression and protein amount of specific MT paralogs are strongly related to life span in mammals. MT expression rather than gene number may influence the high Cd levels and longevity of some species. In support of this, we found that overexpression of MT-1 accelerated Cd accumulation in mice and that tissue Cd was higher in long-lived mouse strains with high MT expression. We conclude that long-lived species have evolved a more efficient stress response by upregulating the expression of MT genes in presence of Cd, which contributes to elevated tissue Cd levels. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00393-3.
- Published
- 2021
31. Association of HERV-K and LINE-1 hypomethylation with reduced disease-free survival in melanoma patients
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Maurizio Cardelli, Marco Malavolta, Michela Di Donato, Eduardo Nagore, Joost van den Oord, Francesco Piacenza, Robertina Giacconi, Lares Larcher, Rajesh Kumar, Sivaramakrishna Rachakonda, Elisa Pierpaoli, Per Arne Andresen, Remco van Doorn, Nelleke A. Gruis, Anders Molven, Dace Pjanova, and Mauro Provinciali
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Disease free survival ,Skin Neoplasms ,Adolescent ,Retroelements ,disease-free survival ,transposon ,viruses ,Biology ,Young Adult ,LINE-1 ,Retrovirus ,Internal medicine ,Genetics ,medicine ,melanoma ,Humans ,Human endogenous retrovirus K ,Nevus ,neoplasms ,Aged ,Neoplasm Staging ,Aged, 80 and over ,DNA methylation ,Melanoma ,Endogenous Retroviruses ,aging ,Terminal Repeat Sequences ,Methylation ,Middle Aged ,HML-2 ,medicine.disease ,biology.organism_classification ,HERV-K ,retrovirus ,Long Interspersed Nucleotide Elements ,Cutaneous melanoma ,embryonic structures ,Biomarker (medicine) ,CpG Islands ,Female ,prognosis ,Neoplasm Recurrence, Local - Abstract
Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence.
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- 2020
32. Prevalence and loads of torquetenovirus in the European MARK-AGE study population
- Author
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Alexander Bürkle, Antti Hervonen, Martijn E.T. Dollé, Ewa Sikora, Claudio Franceschi, Efstathios S. Gonos, Wolfgang Stuetz, Eugenio Mocchegiani, Marco Malavolta, Miriam Capri, Eline Slagboom, Pietro Giorgio Spezia, Mauro Provinciali, Mikko Hurme, Magdalena Dudkowska, Christiane Schön, Mauro Pistello, Maria Moreno-Villanueva, Olivier Toussaint, Fabrizio Maggi, Nicolle Breusing, Jürgen Bernhardt, Eugène H.J.M. Jansen, Francesco Piacenza, Robertina Giacconi, Lisa Macera, Beatrix Grubeck-Loebenstein, Florence Debacq-Chainiaux, Dorota Janiszewska, Andrea Basso, Tilman Grune, and Giacconi R, Maggi F, Macera L, Spezia PG, Pistello M, Provinciali M, Piacenza F, Basso A, Bürkle A, Moreno-Villanueva M, Dollé MET, Jansen E, Grune T, Stuetz W, Gonos ES, Schön C, Bernhardt J, Grubeck-Loebenstein B, Sikora E, Dudkowska M, Janiszewska D, Toussaint O, Chainiaux FD, Franceschi C, Capri M, Hervonen A, Hurme M, Slagboom E, Breusing N, Mocchegiani E, Malavolta M.
- Subjects
Adult ,Male ,Aging ,TTV, aging, immunosenescence, CD4/CD8 ratio, Down syndrome ,Offspring ,Immunosenescence ,Down syndrome ,Population ,CD4-CD8 Ratio ,Cytomegalovirus ,Viremia ,TTV ,03 medical and health sciences ,0302 clinical medicine ,CD4/CD8 ratio ,Prevalence ,Humans ,Medicine ,Lymphocyte Count ,030212 general & internal medicine ,education ,Aged ,030304 developmental biology ,Torque teno virus ,0303 health sciences ,education.field_of_study ,business.industry ,Age Factors ,Odds ratio ,Middle Aged ,Viral Load ,medicine.disease ,DNA Virus Infections ,Confidence interval ,3. Good health ,Europe ,Cross-Sectional Studies ,Immunology ,aging ,immunosenescence ,Population study ,Female ,Geriatrics and Gerontology ,Human Aging ,business ,ddc:900 - Abstract
Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians [GO]) and premature (Down syndrome [DS]) immunosenescence. The TTV load was positively associated with age, cytomegalovirus (CMV) antibody levels, and the Cu/Zn ratio and negatively associated with platelets, total cholesterol, and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (Randomly Recruited Age-Stratified Individuals From The General Population) populations. In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with ≥4log TTV copies/mL had a higher risk of having a CD4/CD8 ratio
- Published
- 2020
33. Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats
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Mauro Provinciali, Marco Malavolta, Robertina Giacconi, Fabrizio Maggi, and Dario Brunetti
- Subjects
senoptotics ,Ruxolitinib ,Aging ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Review ,Azithromycin ,Bioinformatics ,Global Health ,Virus ,Anti-Infective Agents ,Pandemic ,Nitriles ,Global health ,Relevance (law) ,Medicine ,Humans ,cellular senescence ,Viral ,Pandemics ,lcsh:QH301-705.5 ,business.industry ,Interleukin-6 ,COVID-19 ,General Medicine ,Pneumonia ,mitochondria ,Pyrimidines ,lcsh:Biology (General) ,SASP inhibitors ,inflammation ,senolytics ,extracellular vesicles ,viral infection ,Cellular Senescence ,Coronavirus Infections ,Pyrazoles ,business ,medicine.drug - Abstract
The higher death rate caused by COVID-19 in older people, especially those with comorbidities, is a challenge for biomedical aging research. Here we explore the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, may drive the deleterious consequences of the infection. Data shows that other RNA viruses, such as influenza virus, can display enhanced replication efficiency in senescent cells, suggesting that the accumulation of senescent cells with aging and age-related diseases may play a role in this phenomenon. However, at present, we are completely unaware of the response to SARS-CoV and SARS-COV-2 occurring in senescent cells. We deem that this is a priority area of research because it could lead to the development of several therapeutic strategies based on senotherapeutics or prevent unsuccessful attempts. Two of these senotherapeutics, azithromycin and ruxolitinib, are currently undergoing testing for their efficacy in treating COVID-19. The potential of these strategies is not only for ameliorating the consequences of the current emergence of SARS-CoV-2, but also for the future emergence of new viruses or mutated ones for which we are completely unprepared and for which no vaccines are available.
- Published
- 2020
34. MetaTropismDB: a database of organ-specific metastasis induced by human cancer cell lines in mouse models
- Author
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Marco Malavolta, Annamaria Ruzzo, Francesco Piacenza, Matteo Giulietti, Marco Bastianoni, Robertina Giacconi, Francesco Piva, Massimo Bracci, and Monia Cecati
- Subjects
Organ specific metastasis ,Database ,Human cell ,Biology ,computer.software_genre ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Metastasis ,Disease Models, Animal ,Mice ,Cell culture ,Neoplasms ,Cancer cell ,Overall survival ,medicine ,AcademicSubjects/SCI00960 ,Animals ,Humans ,Original Article ,General Agricultural and Biological Sciences ,computer ,Human cancer ,Information Systems - Abstract
The organotropism is the propensity of metastatic cancer cells to colonize preferably certain distant organs, resulting in a non-random distribution of metastases. In order to shed light on this behaviour, several studies were performed by the injection of human cancer cell lines into immunocompromised mouse models. However, the information about these experiments is spread in the literature. For each xenograft experiment reported in the literature, we annotated both the experimental conditions and outcomes, including details on inoculated human cell lines, mouse models, injection methods, sites of metastasis, organs not colonized, rate of metastasis, latency time, overall survival and the involved genes. We created MetaTropismDB, a freely available database collecting hand-curated data useful to highlight the mechanisms of organ-specific metastasis. Currently, it stores the results of 513 experiments in which injections of 219 human cell lines have been carried out in mouse models. Notably, 296 genes involved in organotropic metastases have been collected. This specialized database allows the researchers to compare the current results about organotropism and plan future experiments in order to identify which tumour molecular signatures establish if and where the metastasis will develop. Database URL: http://www.introni.it/Metastasis/metastasis.html
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- 2020
35. Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects
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Robertina Giacconi, Roberta Galeazzi, Lisa Macera, Lorenzo Nisi, Francesco Martelli, Francesco Piacenza, Simone Giannecchini, Fabrizio Maggi, Sara Galimberti, Marco Malavolta, Erminia Mariani, Laura Costarelli, Lorenzo Iovino, Mauro Provinciali, Mauro Pistello, Pietro Giorgio Spezia, Giacconi, Robertina, Maggi, Fabrizio, Macera, Lisa, Pistello, Mauro, Provinciali, Mauro, Giannecchini, Simone, Martelli, Francesco, Spezia, Pietro Giorgio, Mariani, Erminia, Galeazzi, Roberta, Costarelli, Laura, Iovino, Lorenzo, Galimberti, Sara, Nisi, Lorenzo, Piacenza, Francesco, and Malavolta, Marco
- Subjects
Male ,0301 basic medicine ,Aging ,Torque teno virus ,Immunesenescence ,Mortality ,NK cell activity ,TTV ,Biochemistry ,Molecular Biology ,Genetics ,Endocrinology ,Cell Biology ,Immunosenescence ,Population ,Viremia ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Genetic ,Cause of Death ,medicine ,Humans ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Mortality rate ,Antibody titer ,Middle Aged ,Viral Load ,medicine.disease ,Killer Cells, Natural ,MicroRNAs ,030104 developmental biology ,Italy ,DNA, Viral ,Immunology ,Linear Models ,Female ,business ,Viral load ,030217 neurology & neurosurgery - Abstract
An age-related dysregulation of immune response, known as immunosenescence, contributes to increased susceptibility to infections, frailty and high risk of mortality in the elderly. Torquetenovirus (TTV), a circular, single-stranded DNA virus, is highly prevalent in the general population and it may persist in the organism, also in association with other viruses such as cytomegalovirus (CMV), causing chronic viremia. The relationship that TTV establishes with the immune system of infected hosts is not clear. It is known that TTV encodes microRNAs (miRNAs) that might contribute to immune evasion and that the highest viral loads are found in peripheral blood cells. Moreover, it is suspected that TTV infection lead to increased production of inflammatory mediators, thus playing a role in immunosenescence. We investigated the association of TTV load and miRNAs expression with inflammatory and immune markers and the influence of TTV load on mortality within a cohort of 379 elderly subjects who were followed up for 3 years. TTV DNA load in polymorphonuclear leukocytes was slightly positively correlated with age and negatively associated with serum albumin levels and NK cell activity. A marginal positive correlation between TTV DNA load, monocytes and IL-8 plasma levels was found in females and males respectively. TTV DNA copies ≥4.0 log represented a strong predictor of mortality (Hazard ratio = 4.78, 95% CI: 1.70-13.44, after adjusting for age, sex and the main predictors of mortality rate) and this association remained significant even after the CMV IgG antibody titer was included in the model (HR = 9.83; 95% CI: 2.48-38.97; N = 343 subjects). Moreover, multiple linear regression model showed that TTV miRNA-t3b of genogroup 3 was inversely associated with triglycerides, monocytes and C-reactive protein, and directly associated with IL6. Overall these findings suggest a role of TTV in immunesenescence and in the prediction of all-cause mortality risk in Italian elderly subjects. Further studies are needed to fully understand the pathogenic mechanisms of TTV infection during aging.
- Published
- 2018
36. Oxidative Stress in Elderly with Different Cognitive Status: My Mind Project
- Author
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Patrizia Fattoretti, Roberta Papa, Laura Costarelli, Cinzia Giuli, Marco Malavolta, Robertina Giacconi, Fabrizia Lattanzio, Cristina Paoloni, Demetrio Postacchini, Roberta Galeazzi, and Paolo Fabbietti
- Subjects
Male ,0301 basic medicine ,Aging ,medicine.medical_specialty ,Disease ,Neuropsychological Tests ,medicine.disease_cause ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Alzheimer Disease ,law ,Intervention (counseling) ,Internal medicine ,Humans ,Medicine ,Elderly people ,Cognitive status ,Cognitive Dysfunction ,Longitudinal Studies ,Prospective Studies ,Aged ,Cognitive Behavioral Therapy ,business.industry ,General Neuroscience ,Cognition ,General Medicine ,Cognitive training ,Oxidative Stress ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,Italy ,Female ,Geriatrics and Gerontology ,Reactive Oxygen Species ,business ,Biomarkers ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
BACKGROUND Biomarkers of oxidative stress have been associated with cognitive status in humans and have been proposed to guide prognosis/treatment in Alzheimer's disease (AD) and mild cognitive impairment (MCI). OBJECTIVE The aim of this study was to compare oxidative stress status in the plasma of mild-moderate AD, MCI, and healthy elderly with normal cognition (HE) undergoing a non-pharmacological intervention including multi-modal cognitive training ("My Mind Project"). METHODS A prospective randomized trial involving 321 elderly people enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental (cognitive training) or to a control group. Cognitive performances and biomarkers have been analyzed before intervention (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2), and after 2 years (follow-up 3). The biological antioxidant potential (BAP) to Diacron reactive oxygen metabolites (d-ROM) ratio has been used as an indicator of oxidative stress status and as outcome variable. RESULTS We have found no differences in the oxidative status among AD, MCI, and HE. Neither did we find a significant effect of the intervention within experimental groups. Gender was the sole factor with a strong significant effect on BAP/d-ROM. CONCLUSIONS Based on these results, the utility of biomarkers of oxidative stress to guide prognosis/treatment in AD or MCI seems to be limited by lack of specificity, large interindividual variability, and gender bias.
- Published
- 2018
37. Implications of impaired zinc homeostasis in diabetic cardiomyopathy and nephropathy
- Author
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Maurizio Cardelli, Laura Costarelli, Mauro Provinciali, Robertina Giacconi, Marco Malavolta, Francesco Piacenza, and Lu Cai
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,chemistry.chemical_element ,030209 endocrinology & metabolism ,Zinc ,Biology ,Biochemistry ,Nephropathy ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,Diabetic cardiomyopathy ,medicine ,Secretion ,Insulin ,General Medicine ,medicine.disease ,030104 developmental biology ,Endocrinology ,chemistry ,Molecular Medicine ,Homeostasis - Abstract
Impaired zinc homeostasis is observed in diabetes mellitus (DM2) and its complications. Zinc has a specific role in pancreatic β-cells via insulin synthesis, storage, and secretion. Intracellular zinc homeostasis is tightly controlled by zinc transporters (ZnT and Zip families) and metallothioneins (MT) which modulate the uptake, storage, and distribution of zinc. Several investigations in animal models demonstrate the protective role of MT in DM2 and its cardiovascular or renal complications, while a copious literature shows that a common polymorphism (R325W) in ZnT8, which affects the protein's zinc transport activity, is associated with increased DM2 risk. Emerging studies highlight a role of other zinc transporters in β-cell function, suggesting that targeting them could make a possible contribution in managing the hyperglycemia in diabetic patients. This article summarizes the current findings concerning the role of zinc homeostasis in DM2 pathogenesis and development of diabetic cardiomyopathy and nephropathy and suggests novel therapeutic targets. © 2017 BioFactors, 43(6):770-784, 2017.
- Published
- 2017
38. Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment
- Author
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Marcello Maggio, Robertina Giacconi, Andrea Basso, Fabrizia Lattanzio, Marco Malavolta, Francesco Piacenza, Laura Costarelli, Mauro Provinciali, and Andrea Corsonello
- Subjects
Transcriptional Activation ,0301 basic medicine ,Senescence ,Aging ,Chemokine ,Lansoprazole ,030204 cardiovascular system & hematology ,Pharmacology ,Fatty acid-binding protein ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,medicine ,Humans ,CXCL11 ,CX3CL1 ,Cells, Cultured ,Cellular Senescence ,Dose-Response Relationship, Drug ,biology ,Endothelial Cells ,Gene Expression Regulation, Developmental ,Proton Pump Inhibitors ,Coronary Vessels ,Phenotype ,030104 developmental biology ,biology.protein ,Cytokines ,Geriatrics and Gerontology ,Transcriptome ,Gerontology ,Omeprazole ,medicine.drug - Abstract
Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment. Here, we show that atherogenic response is among the most regulated processes in PPI-treated HCAECs. PPIs induced down-regulation of anti-atherogenic chemokines (CXCL11, CXCL12 and CX3CL1) in senescent but not in non-senescent cells, while the same chemokines were up-regulated in untreated senescent cells. These findings support the hypothesis that up-regulated anti-atherogenic chemokines may represent a defensive mechanism against atherosclerosis during cellular senescence, and suggest that PPIs could activate pro-atherogenic pathways by changing the secretory phenotype of senescent HCAECs. Moreover, the genes coding for fatty acid binding protein 4 (FABP4) and piezo-type mechanosensitive ion channel component 2 (PIEZO2) were modulated by PPIs treatment with respect to untreated cells. In conclusions, our results show that long-term and high dose use of PPI could change the secretory phenotype of senescent cells, suggesting one of the potential mechanisms by which use of PPI can increase adverse outcomes in older subjects.
- Published
- 2016
39. FKBP5 Polymorphism, Coping and Emotional Status in Chronic Obstructive Pulmonary Disease Patients Undergoing Pulmonary Rehabilitation
- Author
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Stefano Bonassi, Carlo Tomino, Mauro Provinciali, Marco Malavolta, Patrizia Russo, Robertina Giacconi, Alberto Ricci, Alessia Santoro, Federica Marcolongo, Giulia Prinzi, Massimo Fini, and Vittorio Cardaci
- Subjects
medicine.medical_specialty ,COPD ,Coping (psychology) ,business.industry ,medicine.medical_treatment ,Pulmonary disease ,medicine.disease ,humanities ,Internal medicine ,physiology ,Medicine ,Anxiety ,Pulmonary rehabilitation ,FKBP5 ,medicine.symptom ,business - Abstract
Background: COPD is characterized by dyspnea, chronic cough, sputum production and extra pulmonary multimorbidity including depression, anxiety and cognitive problems. Methods: Cognitive and psychological clinical alterations/disorders; QoL/Health-related QoL; and Coping strategies were evaluated in 71 COPD patients characterized for FKBP5 gene (rs4713916). Instruments: MMSE, MoCA, ROCF, BDI-II, CES-D, SAS, SF-36, ADL, IADL, SGRQ, MRF 26, CIRS, Brief COPE. Results: Carriers of the rs4713916 polymorphisms (G:A) show better cognitive performances, higher degree of independence in the ADL and IADL, better QoL before and after rehabilitation, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorder, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant anti-psychotic, hypnotic-sedative drugs. On the other hand, no difference was found as regards the number of comorbidities. Conclusions: Our study shows that rs4713916 is positively associated with better outcome for COPD. These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical and behavioral features of COPD patients.. Our data may be used as initial benchmark for future clinical studies.
- Published
- 2019
40. Prognosis and Interplay of Cognitive Impairment and Sarcopenia in Older Adults Discharged from Acute Care Hospitals
- Author
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Paolo Fabbietti, Francesco Guarasci, Stefano Volpato, Carmelinda Ruggiero, Antonio Cherubini, Fabrizia Lattanzio, Davide L. Vetrano, Giovanni Renato Riccardi, Lucia Mancinelli, Daniele Castellani, Andrea Corsonello, Elisa Zengarini, Graziano Onder, and Robertina Giacconi
- Subjects
medicine.medical_specialty ,cognitive impairment ,hospital ,mortality ,older patients ,sarcopenia ,Socio-culturale ,lcsh:Medicine ,Article ,03 medical and health sciences ,0302 clinical medicine ,Acute care ,Internal medicine ,Medicine ,Dementia ,LS4_4 ,030212 general & internal medicine ,cognitive impairment, hospital, mortality, older patients, sarcopenia ,Geriatrics ,business.industry ,lcsh:R ,Confounding ,Cognition ,General Medicine ,medicine.disease ,Comorbidity ,Sarcopenia ,Underweight ,medicine.symptom ,business ,human activities ,030217 neurology & neurosurgery - Abstract
Sarcopenia and cognitive impairment are associated with an increased risk of negative outcomes, but their prognostic interplay has not been investigated so far. We aimed to investigate the prognostic interaction of sarcopenia and cognitive impairment concerning 12-month mortality among older patients discharged from acute care wards in Italy. Our series consisted of 624 patients (age = 80.1 ±, 7.0 years, 56.1% women) enrolled in a prospective observational study. Sarcopenia was defined following the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Cognitive impairment was defined as age- and education-adjusted Mini-Mental State Examination (MMSE) score <, 24 or recorded diagnosis of dementia. The study outcome was all-cause mortality during 12-month follow-up. The combination of sarcopenia and cognitive ability was tested against participants with intact cognitive ability and without sarcopenia. Overall, 159 patients (25.5%) were identified as having sarcopenia, and 323 (51.8%) were cognitively impaired. During the follow-up, 79 patients (12.7%) died. After adjusting for potential confounders, the combination of sarcopenia and cognitive impairment has been found associated with increased mortality (HR = 2.12, 95% CI = 1.05&ndash, 4.13). Such association was also confirmed after excluding patients with dementia (HR = 2.13, 95% CI = 1.06&ndash, 4.17), underweight (HR = 2.18, 95% CI = 1.03&ndash, 3.91), high comorbidity burden (HR = 2.63, 95% CI = 1.09&ndash, 6.32), and severe disability (HR = 2.88, 95% CI = 1.10&ndash, 5.73). The co-occurrence of sarcopenia and cognitive impairment may predict 1-year mortality in older patients discharged from acute care hospitals.
- Published
- 2019
41. FKBP5 rs4713916: A Potential Genetic Predictor of Interindividual Different Response to Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease in a Real-Life Setting
- Author
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Marco Malavolta, Mauro Magnani, Robertina Giacconi, Vittorio Cardaci, Patrizia Russo, Massimo Fini, Alessia Santoro, Aliaksei Kisialiou, Mauro Provinciali, Carlo Tomino, Stefania Proietti, Giulia Prinzi, Francesco Collacchi, and Stefano Bonassi
- Subjects
Male ,0301 basic medicine ,Exacerbation ,medicine.medical_treatment ,lcsh:Chemistry ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Adrenal Cortex Hormones ,Genotype ,Medicine ,lcsh:QH301-705.5 ,Spectroscopy ,Aged, 80 and over ,COPD ,rehabilomics ,General Medicine ,Middle Aged ,Computer Science Applications ,Treatment Outcome ,inhaled corticosteroid ,lung function ,rs37972 ,rs471396 ,Female ,FKBP5 ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,Catalysis ,Tacrolimus Binding Proteins ,Inorganic Chemistry ,03 medical and health sciences ,Receptors, Glucocorticoid ,Internal medicine ,Administration, Inhalation ,Humans ,Pulmonary rehabilitation ,Physical and Theoretical Chemistry ,Molecular Biology ,Aged ,business.industry ,Organic Chemistry ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030228 respiratory system ,Disease Presentation ,Pharmacogenomics ,business - Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient&rsquo, s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed, namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.
- Published
- 2019
42. Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence
- Author
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Andrea Basso, Mauro Provinciali, Elisa Pierpaoli, Maurizio Cardelli, Francesco Piacenza, Robertina Giacconi, and Marco Malavolta
- Subjects
0301 basic medicine ,medicine.diagnostic_test ,medicine.drug_class ,Vitamin E ,medicine.medical_treatment ,Inflammation ,Review ,Biology ,Phenotype ,General Biochemistry, Genetics and Molecular Biology ,In vitro ,Anti-inflammatory ,03 medical and health sciences ,030104 developmental biology ,In vivo ,medicine ,Cancer research ,medicine.symptom ,Lipid profile ,PI3K/AKT/mTOR pathway - Abstract
Tocotrienols (T3) have been shown to represent a very important part of the vitamin E family since they have opened new opportunities to prevent or treat a multitude of age-related chronic diseases. The beneficial effects of T3 include the amelioration of lipid profile, the promotion of Nrf2 mediated cytoprotective activity and the suppression of inflammation. All these effects may be the consequence of the ability of T3 to target multiple pathways. We here propose that these effects may be the result of a single target of T3, namely senescent cells. Indeed, T3 may act by a direct suppression of the senescence-associated secretory phenotype (SASP) produced by senescent cells, mediated by inhibition of NF-kB and mTOR, or may potentially remove the origin of the SASP trough senolysis (selective death of senescent cells). Further studies addressed to investigate the impact of T3 on cellular senescence “in vitro” as well as in experimental models of age-related diseases “in vivo” are clearly encouraged.
- Published
- 2018
43. Reduced levels of plasma selenium are associated with increased inflammation and cardiovascular disease in an Italian elderly population
- Author
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Leonardo Chiodi, Marco Malavolta, Francesco Piacenza, Robertina Giacconi, Laura Costarelli, Mauro Provinciali, and Gianfranco Boccoli
- Subjects
0301 basic medicine ,Aging ,Chemokine ,medicine.medical_specialty ,Lymphocyte ,Inflammation ,Disease ,Logistic regression ,Biochemistry ,Peripheral blood mononuclear cell ,CCL5 ,Selenium ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Genetics ,medicine ,Humans ,Molecular Biology ,Aged ,Aged, 80 and over ,biology ,business.industry ,Cell Biology ,Micronutrient ,030104 developmental biology ,medicine.anatomical_structure ,Italy ,Cardiovascular Diseases ,Leukocytes, Mononuclear ,biology.protein ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Selenium (Se) is an essential micronutrient for human health that protects from oxidative damage. Se deficiency has been associated with the development of cardiovascular diseases (CVD). In this study we aimed to investigate the association between Se status, CVD risk, cardio-metabolic and inflammatory markers in elderly population. Se Plasma levels and inflammatory markers [neutrophil/lymphocyte ratio, serum C-reactive protein (CRP) levels and Copper/Zinc ratio (Cu/Zn)] were measured in 858 control subjects (mean age 73.4 ± 9.3) and 606 CVD patients (mean age 72.5± 8.7). A multivariate logistic regression was performed to evaluate the association between Se deficiency (Se60 μg/L) and the risk of CDV. In a subgroup of 46 CVD patients the gene expression of IL-1β, CCL5/RANTES, IL-6, IL-8, IL-10, platelet-derived growth factor-β (PDGFβ) and sirtuins in peripheral blood mononuclear cell (PBMC) were further examined. Increased values of neutrophil/lymphocyte ratio, CRP levels and Cu/Zn ratio were observed in Se deficiency condition both in controls and in CVD patients. Moreover, enhanced gene expression of cytokines and chemokines such as IL1β, CCL5 and PDGF- β, and a downregulation of SIRT-1, SIRT-5, SIRT-6, SIRT-7 were found in PBMCs from CVD patients with Se deficiency. A multivariate logistic regression showed that Se deficiency was associated with an increased CVD risk (odds ratio=1.946, 95% CI: 1.19-3.18, p0.01). The current study revealed that Se deficiency is independently associated with CVD, and with elevated circulating inflammatory markers and affects the expression of cytokines, chemokines and sirtuins in PBMCs.
- Published
- 2021
44. My Mind Project: the effects of cognitive training for elderly—the study protocol of a prospective randomized intervention study
- Author
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E. Mocchegiani, Laura Costarelli, Patrizia Fattoretti, Marco Malavolta, Roberta Papa, Robertina Giacconi, Fabrizia Lattanzio, Cristina Gagliardi, Marta Balietti, Domenico Venarucci, Demetrio Postacchini, Cinzia Giuli, and Tiziana Casoli
- Subjects
0301 basic medicine ,Aging ,medicine.medical_specialty ,Elderly people ,03 medical and health sciences ,0302 clinical medicine ,Clinical Protocols ,Alzheimer Disease ,Memory ,medicine ,Dementia ,Humans ,Cognitive Dysfunction ,Prospective Studies ,Cognitive decline ,Prospective cohort study ,Aged ,Protocol (science) ,Public health ,Mild cognitive impairment ,medicine.disease ,Cognitive training ,Ageing ,030104 developmental biology ,Italy ,Original Article ,Geriatrics and Gerontology ,Alzheimer's disease ,Psychology ,Alzheimer’s disease ,030217 neurology & neurosurgery ,Independent living ,Biomarkers ,Clinical psychology - Abstract
Background Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward. Aims To describe the study protocol and methods of “My Mind Project: the effect of cognitive training for elderly” (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild–moderate Alzheimer’s disease, mild cognitive impairment and normal cognitive functioning. Methods The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). Discussion The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline. Conclusion The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.
- Published
- 2016
45. Effect of ZIP2 Gln/Arg/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation
- Author
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Marco Malavolta, Erminia Mariani, George Dedoussis, Robertina Giacconi, Tamas Fulop, Georges Herbein, Maurizio Cardelli, Francesco Piacenza, Laura Costarelli, Jolanta Jajte, Mauro Provinciali, Nazzarena Gasparini, Eugenio Mocchegiani, Franco Busco, Lothar Rink, Andrea Basso, and Roberta Galeazzi
- Subjects
medicine.medical_specialty ,biology ,Clinical Biochemistry ,chemistry.chemical_element ,Inflammation ,General Medicine ,Zinc ,Biochemistry ,Proinflammatory cytokine ,Endocrinology ,Immune system ,Downregulation and upregulation ,chemistry ,Internal medicine ,medicine ,biology.protein ,Molecular Medicine ,Tumor necrosis factor alpha ,medicine.symptom ,Interleukin 6 ,Homeostasis - Abstract
Zinc dyshomeostasis may lead to an augmented production of proinflammatory cytokines promoting chronic inflammation and increasing the susceptibility to age-related diseases. Several studies suggest that the zinc transporter protein ZIP2 may play a relevant role in the immune system especially during zinc deficiency, while a polymorphism on the coding region of ZIP2 gene (Gln/Arg/Leu) has been associated with severe carotid artery disease. The aim of this study is to investigate the role of ZIP2 SNP on zinc and inflammatory status in 1090 elderly healthy free-living subjects enrolled in the ZincAge project and to assess the effect of zinc supplementation on zinc status, inflammatory mediators, and zinc transporter expression depending on ZIP2 genotype. ZIP2 Leu- (Arg43Arg) carriers showed enhanced IL-6, TNF-α, and RANTES plasma levels associated with decreased free cytosolic zinc in PBMCs and an upregulation of zinc transporters ZIP2, ZIP8, and Znt1. Moreover, Leu- subjects displayed significant decrement of inflammatory mediators such as MCP-1, TNF-α, and RANTES following zinc supplementation. In summary, this investigation provides new evidence on the effect of ZIP2 Gln/Arg/Leu polymorphism on proinflammatory mediators and zinc homeostasis in elderly population with a more pronounced anti-inflammatory effect of zinc supplementation in subjects carrying ZIP2 Leu- (Arg43Arg) genotype. These novel findings could be useful in identifying elderly subjects who may benefit of zinc intervention to decrease the inflammatory status and to prevent or delay the development of age-related diseases.
- Published
- 2015
46. Serum copper to zinc ratio: Relationship with aging and health status
- Author
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Francesco Piacenza, Eugenio Mocchegiani, Andrea Basso, Marco Malavolta, Robertina Giacconi, and Laura Costarelli
- Subjects
Aging ,medicine.medical_specialty ,Serum copper ,chemistry.chemical_element ,Inflammation ,Zinc ,Serum concentration ,Biology ,3. Good health ,Ageing ,Endocrinology ,chemistry ,Internal medicine ,Chronic Disease ,medicine ,Animals ,Humans ,medicine.symptom ,Copper ,Homeostasis ,Developmental Biology - Abstract
The serum concentrations of copper (Cu) and zinc (Zn) are strictly regulated by compensatory mechanisms that act to stabilize them within certain ranges of nutritional intake. However, there are mechanisms that are built to decrease serum concentration of Zn and to increase serum concentration of Cu in the presence of inflammatory conditions, so that a common feature of several age-related chronic diseases is an increase of the Cu to Zn ratio (CZr). Although the clinical potential of CZr has been extensively investigated, few authors addressed the mechanisms that mainly contribute to the increase of CZr in serum during aging, which signals drive this change and how cells respond to these changes. This review focuses on this topic and discusses how an increase of CZr during aging could reflect the homeostatic shade from a general systemic "growth and reproduction" status typical of juvenile age to a "repair and maintenance" status that evolved to preserve health status during old age.
- Published
- 2015
47. COVID-19 and smoking: is nicotine the hidden link?
- Author
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Marco Malavolta, Carlo Tomino, Fabrizio Maggi, Stefano Bonassi, Robertina Giacconi, and Patrizia Russo
- Subjects
Pulmonary and Respiratory Medicine ,Chronic Obstructive ,Nicotine ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Pulmonary disease ,complex mixtures ,Pulmonary Disease ,Betacoronavirus ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Correspondence ,Humans ,Medicine ,Viral ,030212 general & internal medicine ,Receptor ,Agora ,Pandemics ,Smokers ,SARS-CoV-2 ,business.industry ,Smoking ,COVID-19 ,Pneumonia ,respiratory system ,Coronavirus Infections ,respiratory tract diseases ,Endocrinology ,nervous system ,030228 respiratory system ,business ,psychological phenomena and processes ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Leung et al. [1] have recently published, in the European Respiratory Journal, a paper on the expression of angiotensin-converting enzyme II (ACE-2) in the small airway epithelia of smokers and COPD patients, discussing its effects on the risk of severe coronavirus disease 2019 (COVID-19). The authors found an increased expression of the ACE-2 gene in the airways of subjects with COPD and in current smokers. Indeed, a recent systematic review reporting data on the smoking habits of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), concluded that smoking may be associated with a negative progression of the disease and with the adverse outcome [2]., Nicotine via alpha7-nicotinic receptor induces ACE-2 overexpression in human bronchial epithelial cells (HBEpC) https://bit.ly/3eJ5b35
- Published
- 2020
48. Zinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project
- Author
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Florence Debacq-Chainiaux, Andrea Basso, Tilman Grune, Paola Caiafa, Marco Malavolta, Ewa Sikora, Michele Zampieri, Nicolle Breusing, Efstathios S. Gonos, Martijn E.T. Dollé, Beatrix Grubeck-Loebenstein, Wolfgang Stuetz, Maria Moreno-Villanueva, Alexander Bürkle, Daniela Weber, Eugenio Mocchegiani, Fabio Ciccarone, Eugène H.J.M. Jansen, Antti Hervonen, Claudio Franceschi, Olivier Toussaint, Laura Costarelli, Eline Slagboom, Christiane Schön, Francesco Piacenza, and Robertina Giacconi
- Subjects
0301 basic medicine ,Male ,Aging ,Lymphocyte ,Cell Culture Techniques ,medicine.disease_cause ,chemistry.chemical_compound ,0302 clinical medicine ,Metallothionein ,Aged, 80 and over ,education.field_of_study ,Middle Aged ,Malondialdehyde ,Flow Cytometry ,Europe ,Zinc ,medicine.anatomical_structure ,Female ,Centenarian ,Senescence ,Adult ,medicine.medical_specialty ,Offspring ,Population ,Longevity ,Real-Time Polymerase Chain Reaction ,metallothionein ,aging ,longevity ,senescence ,zinc ,03 medical and health sciences ,Internal medicine ,ddc:570 ,medicine ,Humans ,Settore BIO/10 ,education ,Aged ,business.industry ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,Cross-Sectional Studies ,chemistry ,Leukocytes, Mononuclear ,RNA ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery ,Oxidative stress ,Biomarkers - Abstract
Metallothionein (MT) family are cysteine-rich proteins that regulate zinc (Zn) homeostasis and protect against oxidative damage. Studies in transgenic mice have shown that MT favorably influence longevity, although their role in human aging is not completely understood. Within the European multicenter study MARK-AGE, we analyzed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2,936 age-stratified subjects (35–75 years) including the general population (RASIG), centenarian offspring (GO), and their spouses (SGO). We found that the lymphocyte capability to induce MT in response to Zn is not affected by aging. However, GO participants showed lower Zn-induced MT and increased basal expression of MT1A, MT1X, and ZnT-1 genes than RASIG subjects. Moreover, Zn-induced MT levels were found to be inversely related with oxidative stress markers (plasma protein carbonyls, 3-nitrotyrosine, and malondialdehyde) in the whole population, but not in GO subjects. In conclusion, our results support the hypothesis that the response to Zn is attenuated in PBMCs of centenarian offspring compared to the general population as a consequence of a tighter control of Zn homeostasis which is likely to provide them constant protection against stress stimuli over the whole lifespan. published
- Published
- 2018
49. Targeting Oxidative Stress in Diabetic Complications: New Insights
- Author
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Robertina Giacconi, Lu Cai, Hao Wu, and Judy B. de Haan
- Subjects
Article Subject ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,010501 environmental sciences ,medicine.disease_cause ,Bioinformatics ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,01 natural sciences ,Antioxidants ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Text mining ,medicine ,Humans ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,Reactive oxygen species ,lcsh:RC648-665 ,business.industry ,Oxidative Stress ,Editorial ,chemistry ,Reactive Oxygen Species ,business ,Oxidative stress - Published
- 2018
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50. Measuring zinc in biological nanovesicles by multiple analytical approaches
- Author
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L. Costarelli, Andrea Basso, Lorenzo Nisi, Mauro Provinciali, Eleonora Pavoni, Marco Farina, Xin Jin, Antonio Morini, Andrea Di Donato, Francesco Piva, Robertina Giacconi, Antje Biesemeier, Marco Malavolta, Francesco Piacenza, Elisa Pierpaoli, James C. M. Hwang, and Maurizio Cardelli
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0301 basic medicine ,Differential centrifugation ,Chemistry ,chemistry.chemical_element ,Zinc ,Mole fraction ,Exosomes ,Microscopy, Atomic Force ,Biochemistry ,Microanalysis ,Exosome ,Microvesicles ,Inorganic Chemistry ,03 medical and health sciences ,030104 developmental biology ,Membrane ,Microscopy, Electron, Transmission ,Transmission electron microscopy ,Biophysics ,Molecular Medicine ,Humans ,Particle Size - Abstract
Exosomes are nanovesicles known to mediate intercellular communication. Although it is established that zinc ions can act as intracellular signaling factors, the measurement of zinc in circulating nanovesicles has not yet been attempted. Providing evidence of the existence of this zinc fraction and methods for its measurement might be important to advance our knowledge of zinc status and its relevance in diseases. Exosomes from 0.5 ml of either fresh or frozen human plasma were isolated by differential centrifugation. A morphological and dimensional evaluation at the nanoscale level was performed by atomic force microscopy (AFM) and Transmission Electron Microscopy (TEM). Energy Dispersive X-Ray Microanalysis (EDX) revealed the elemental composition of exosomes and their respective total Zinc content on a quantitative basis. The zinc mole fraction (in at%) was correlated to the phosphorous mole fraction, which is indicative for exosomal membrane material. Both fresh (Zn/P 0.09 ± 0.01) and frozen exosomes (Zn/P 0.08 ± 0.02) had a significant zinc content, which increased up to 1.09 ± 0.12 for frozen exosomes when treated with increasing amounts of zinc (100-500 μM; each p 0.05). Interestingly, after zinc addition, the Calcium mole fractions decreased accordingly suggesting a possible exchange by zinc. In order to estimate the intra-exosomal labile zinc content, an Imaging Flow Cytometry approach was developed by using the specific membrane permeable zinc-probe Fluozin-3AM. A labile zinc content of 0.59 ± 0.27 nM was calculated but it is likely that the measurement may be affected by purification and isolation conditions. This study suggests that circulating nano-vesicular-zinc can represent a newly discovered zinc fraction in the blood plasma whose functional and biological properties will have to be further investigated in future studies.
- Published
- 2017
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