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1. The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans Authors' names and affiliations

Author

Moreau, Jean-Francois, Pradeu, Thomas, Grignolio, Andrea, Nardini, Christine, Castiglione, Filippo, Tieri, Paolo, Capri, Miriam, Salvioli, Stefano, Taupin, Jean-Luc, Garagnani, Paolo, Franceschi, Claudio, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Paris 1 Panthéon-Sorbonne (UP1)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Politecnico di Milano [Milan] (POLIMI), CIG - Interdepartmental Center 'L.Galvani', Centro Interdipartimentale Galvani (CIG), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Departmento of Experimental, Diagnostic and Specialty Medicine, Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 637647,H2020,ERC-2014-STG,IDEM(2015), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Pradeu, Thomas, Immunity, DEvelopment and Microbiota: Understanding the Continuous Construction of Biological Identity - IDEM - - H20202015-09-01 - 2020-09-01 - 637647 - VALID, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Università degli Studi di Roma 'La Sapienza' [Rome], and Università di Bologna [Bologna] (UNIBO)

Subjects
Mobility, [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, Aging, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SHS.HISPHILSO] Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, Immunosenescence, Immune cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Extracellular matrix
Abstract

International audience; Immunosenescence is thought to result from cellular aging and to reflect exposure to environmental stressors and antigens, including cytomegalovirus (CMV). However, not all of the features of immunosenescence are consistent with this view, and this has led to the emergence of the sister theory of " inflammaging ". The recently discovered diffuse tissue distribution of resident memory T cells (TRM) which don't recirculate, calls these theories into question. These cells account for most T cells residing in barrier epithelia which sit in and travel through the extracellular matrix (ECM). With almost all studies to date carried out on peripheral blood, the age-related changes of the ECM and their consequences for T cell mobility, which is crucial for the function of these cells, have been largely ignored. We propose an update of the theoretical framework of immunosenescence, based on a novel hypothesis: the increasing stiffness and cross-linking of the senescent ECM lead to a progressive immunodeficiency due to an age-related decrease in T cell mobility and eventually the death of these cells. A key element of this mechanism is the mechanical stress to which the cell cytoplasm and nucleus are subjected during passage through the ECM. This hypothesis is based on an " evo-devo " perspective bringing together some major characteristics of aging, to create a single interpretive framework for immunosenescence.

Published
2017
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2. MARK-AGE biomarkers of ageing

Author

Jürgen Bernhard, Mikko Hurme, P. Eline Slagboom, Paola Caiafa, Tilman Grune, Alexander Bürkle, Olivier Toussaint, Michel Salmon, Daniela Gradinaru, Eugenio Mocchegiani, Efstathios S. Gonos, Ewa Sikora, Antti Hervonen, Claudio Franceschi, Peter Kristensen, Martijn E.T. Dollé, Sebastiano Collino, Beatrix Grubeck-Loebenstein, Maria A. Blasco, Duncan Talbot, Andreas Simm, Richard Aspinall, Claude Libert, Helen R. Griffiths, Jan H.J. Hoeijmakers, Gerben Zondag, Bertrand Friguet, Miriam Capri, Nicolle Breusing, Maria Moreno-Villanueva, University of Konstanz, BioTeSys GmbH, Esslingen, Spanish National Cancer Research Center (CNIO), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Université de Namur [Namur] (UNamur), Institute for Biomedical Aging Research, University of Innsbruck, Translational Research Center of Nutrition and Ageing (IRCCS-INRCA), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], National Hellenic Research Foundation, Nencki Institute of Experimental Biology, National Institute of Geriatrics and Gerontology 'Ana Aslan', National Institute for Public Health and the Environment [Bilthoven] (RIVM), Straticell, Science Park Crealys, Department of Engineering – BCE Protein Engineering, School of Life and Health Sciences, Aston University [Birmingham], Department for Molecular Biomedical Research (DFMBR), Universiteit Gent = Ghent University [Belgium] (UGENT)-VIB, University of Hohenheim, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University Hospital Halle, CIG - Interdepartmental Center 'L.Galvani', Leiden University Medical Center (LUMC), Department of Cellular Biotechnologies and Hematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical School, University of Tampere [Finland], The MARK-AGE project has received funding from the European Union’s FP7 research and innovation programme under grant agreement HEALTH-F4-2008-200880, European Project: 200880,EC:FP7:HEALTH,FP7-HEALTH-2007-A,MARK-AGE(2008), Leopold Franzens Universität Innsbruck - University of Innsbruck, Universiteit Gent = Ghent University (UGENT)-VIB, Universiteit Leiden, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bürkle, Alexander, Moreno-Villanueva, María, Bernhard, Jürgen, Blasco, María, Zondag, Gerben, Hoeijmakers, Jan H.J., Toussaint, Olivier, Grubeck-Loebenstein, Beatrix, Mocchegiani, Eugenio, Collino, Sebastiano, Gonos, Efstathios S., Sikora, Ewa, Gradinaru, Daniela, Dollé, Martijn, Salmon, Michel, Kristensen, Peter, Griffiths, Helen R., Libert, Claude, Grune, Tilman, Breusing, Nicolle, Simm, Andrea, Franceschi, Claudio, Capri, Miriam, Talbot, Duncan, Caiafa, Paola, Friguet, Bertrand, Slagboom, P. Eline, Hervonen, Antti, Hurme, Mikko, Aspinall, Richard, Molecular Genetics, Spanish National Cancer Research Centre (CNIO), Université de Namur [Namur], Ghent University [Belgium] (UGENT)-VIB, Friedrich-Schiller-Universität Jena, Università degli Studi di Roma 'La Sapienza' [Rome], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Gerontology, Aging, MITOCHONDRIAL-DNA, Biological age, Single measurement, Scientific literature, Biology, 03 medical and health sciences, OLD-AGE, 0302 clinical medicine, Ageing biomarker, T-CELL SUBSETS, ddc:570, Humans, Ageing biomarkers, European commission, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, European Union, OXIDATIVE STRESS, 030304 developmental biology, Genetics, 0303 health sciences, INDUCED PREMATURE SENESCENCE, Human studies, Biology and Life Sciences, Human studie, APOLIPOPROTEIN-E GENOTYPE, REPLICATIVE SENESCENCE, MARK-AGE, Ageing, C-REACTIVE-PROTEIN, Human longevity, TELOMERE LENGTH, Female, Biomarkers, HUMAN LONGEVITY, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Published
2015
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3. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The 'RISTOMED project': Randomized controlled trial in healthy older people

Author

FISCHER, André, BLANC-BISSON, Christèle, DONINI, Lorenzo Maria, VALENTINI, Luzia, PINTO, Alessandro, BOURDEL-MARCHASSON, Isabelle, OSTAN, Rita, BRIGIDI, Patrizia, TURRONI, Silvia, HRELIA, Silvana, HRELIA, Patrizia, BERESWILL, Stefan, LEONCINI, Emanuela, MALAGUTI, Marco, ELE BLANC-BISSON, Christ, DURRIEU, Jessica, SPAZZAFUMO, Liana, BUCCOLINI, Fabio, PRYEN, Florence, DONINI, Lorenzo, FRANCESCHI, Claudio, LOCHS, Herbert, Valentini L, Pinto A, Bourdel-Marchasson I, Ostan R, Brigidi P, Turroni S, Hrelia S, Hrelia P, Bereswill S, Fischer A, Leoncini E, Malaguti M, Blanc-Bisson C, Durrieu J, Spazzafumo L, Buccolini F, Pryen F, Donini LM, Franceschi C, Lochs H., Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre de Gériatrie, CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Université de Bordeaux (UB), Neuropathology Group, European Neuroscience Institute, University of Bologna, CIG - Interdepartmental Center 'L.Galvani', and Dept. of Gastroenterology, Hepatology and Endocrinology

Subjects
Blood Glucose, Male, Homocysteine, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Gastroenterology, law.invention, chemistry.chemical_compound, Probiotic, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, Streptococcus thermophilus, 2. Zero hunger, Aged, 80 and over, 0303 health sciences, Lactobacillus delbrueckii, Nutrition and Dietetics, VSL#3, 3. Good health, Intestines, Vitamin B 12, C-Reactive Protein, Cholesterol, Female, medicine.symptom, Inflammation Oxidative stress Aging VSL#3 Internet Nutritional software, medicine.medical_specialty, Subgroup analysis, Inflammation, 03 medical and health sciences, Folic Acid, Internal medicine, medicine, Humans, Vitamin B12, 030304 developmental biology, Aged, Internet, Biological Products, business.industry, Probiotics, aging, Feeding Behavior, Diet, Gastrointestinal Microbiome, Lactobacillus, Oxidative Stress, chemistry, Immunology, Dietary Supplements, Nutritional software, Oxidative stre, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Lactobacillus plantarum
Abstract

OBJECTIVES: To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years. DESIGN: Open label, randomized, multicenter study. PRIMARY ENDPOINT: High-sensitivity C-reactive protein. SETTING: Community. INTERVENTIONS: Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress. MEASUREMENTS: Blood and stool samples were collected on days 1 and 56. RESULTS: Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP

Published
2014
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4. Ageing, longevity, exceptional longevity and related genetic and non genetics markers: panel statement

Author

Peter Avery, Claudio Franceschi, Calogero Caruso, Dimitri P. Mikhailidis, Genovefa Kolovou, Niki Katsiki, George Panotopoulos, Helen Bilianou, Ewa Sikora, Irene P. Tzanetakou, Nir Barzilai, Miriam Capri, Athanase Benetos, Avery, Peter, Barzilai, Nir, Benetos, Athanase, Bilianou, Helen, Capri, Miriam, Caruso, Calogero, Franceschi, Claudio, Katsiki, Niki, Mikhailidis, Dimitri P, Panotopoulos, George, Sikora, Ewa, Tzanetakou, Irene P, Kolovou, Genovefa, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CIG - Interdepartmental Center 'L.Galvani', Department of Pathobiology and Medical and Forensic Biotechnologies, Università degli studi di Palermo - University of Palermo, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Nencki Institute of Experimental Biology, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Avery, P, Barzilai, N, Benetos, A, Bilianou, H, Capri, M, Caruso, C, Franceschi, C, Katsiki, N, Mikhailidis, DP, Panotopoulos, G, Sikora, E, Tzanetakou, IP, and Kolovou, G

Subjects
Genetic Markers, Gerontology, Aging, Statement (logic), media_common.quotation_subject, Longevity, MESH: Genetic Markers, Biology, MESH: Phenotype, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Genetic Marker, Animals, Humans, MESH: Aging, MESH: Animals, ComputingMilieux_MISCELLANEOUS, media_common, Pharmacology, MESH: Humans, Animal, Congresses as Topic, Phenotype, Ageing, Longevity, Age-related diseases, MESH: Longevity, Ageing, Biological Marker, MESH: Biomarkers, Cardiology and Cardiovascular Medicine, MESH: Congresses as Topic, Biomarkers, Human
Abstract

In May 2012, a group of scientists and clinicians met in Athens (Greece) to consider the relevance of ageing, longevity, exceptional longevity and related genetic and non genetic markers. During this meeting, we firstly reviewed recent epidemiological and clinical studies on ageing, longevity and exceptional longevity, briefly analysed the ageing theories and discussed successful and unsuccessful ageing also taking into account the evolutionary perspective. Secondly, we considered the three phenotypes based on the definition of ageing, longevity and exceptional longevity and the associated biomarkers. Third, we discussed proposed treatments suitable to counteract or slow down ageing. Finally, this panel produced a consensus statement to highlight the importance of ageing, longevity and exceptional longevity, since this is a rapidly increasing phenotype worldwide. We acknowledge that not all experts in this field may completely agree with this statement.

Published
2014
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5. Human longevity within an evolutionary perspective: The peculiar paradigm of a postreproductive genetics

Author

Daniela Mari, Giovannella Baggio, Calogero Caruso, Giovanna De Benedictis, Claudio Franceschi, Miriam Capri, Daniela Monti, Fabiola Olivieri, Stefano Salvioli, Paolo Sansoni, Giuseppe Passarino, Francesca Marchegiani, Sonya Vasto, Giuseppina Candore, CAPRI, M, SALVIOLI, S, MONTI, D, CARUSO, C, CANDORE, G, VASTO, S, OLIVIERI, F, MARCHEGIANI, F, SANSONI, P, BAGGIO, G, MARI, D, PASSARINO, G, DE BENEDICTIS, G, FRANCESCHI, C, Capri M., Salvioli S., Monti D., Caruso C., Vasto S., Olivieri F., Marchegiani F, Sansoni P., Baggio G., Mari D., Passarino G., De Benedictis G., Franceschi C., Department of Experimental Pathology, CIG - Interdepartmental Center 'L.Galvani', Department of Oncology and Experimental Pathology, Department of Pathobiology and Biomedical Methodologies, Università degli studi di Palermo - University of Palermo, Department of Gerontological Sciences, Department of Internal Medicine, University of Parma = Università degli studi di Parma [Parme, Italie], University Hospital, Department of Cell Biology, and Università della Calabria [Arcavacata di Rende] (Unical)

Subjects
Male, Aging, Mitochondrial DNA, Genotype, media_common.quotation_subject, Longevity, Population, Biology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Genetics, Humans, Family, education, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, media_common, Aged, 80 and over, 0303 health sciences, education.field_of_study, Polymorphism, Genetic, Reproduction, Cell Biology, Adaptation, Physiological, Biological Evolution, Phenotype, Human longevity, Gene Expression Regulation, Homo sapiens, Ageing, Evolutionary biology, Trait, Medicine, Female, Identification (biology), postreproductive genetics, 030217 neurology & neurosurgery
Abstract

The data we collected on the genetics of human longevity, mostly resulting from studies on centenarians, indicate that: (1) centenarians and long-living sib-pairs are a good choice for the study of human longevity, because they represent an extreme phenotype, i.e., the survival tail of the population who escaped neonatal mortality, pre-antibiotic era illnesses, and fatal outcomes of age-related complex diseases. (2) The model of centenarians is not simply an additional model with respect to well-studied organisms, and the study of humans has revealed characteristics of ageing and longevity (geographical and sex differences, role of antigenic load and inflammation, role of mtDNA variants) which did not emerge from studies in laboratory model systems and organisms. (3) All the phenotypic characteristics of nonagenarians and centenarians fit the hypothesis that ageing is a remodelling process where the body of survivors progressively adapts to internal and external damaging agents they are exposed to during several decades, largely unpredicted by evolution. (4) Such a remodelling process, which can be considered a Darwinian process occurring at the somatic level within the framework of the evolutionary constraints, established by evolution for Homo sapiens as a species, may explain why the same gene polymorphism can have different (beneficial or detrimental) effects at different ages. (5) Geographic and demographic evidence suggest that longevity can be achieved by different combinations of genes, environment, and chance quantitatively and qualitatively different in many geographic areas, and that population-specific genetic factors, play a role on the longevity trait. (6) The concomitant and integrated use of new in silico and high throughput strategies will greatly accelerate the identification of new longevity genes in humans.

Published
2008
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6. In Vitro Exposure of Human Lymphocytes to 900 MHz CW and GSM Modulated Radiofrequency: Studies of Proliferation, Apoptosis and Mitochondrial Membrane Potential

Author

Elena Scarcella, C. Agostini, Stefano Salvioli, Enrica Bianchi, Andrea Schiavoni, Cristiana Fumelli, Gastone Castellani, Miriam Capri, Ferdinando Bersani, Claudio Franceschi, Pietro Mesirca, Almerino Antolini, CIG - Interdepartmental Center 'L.Galvani', Perimeter Institute for Theoretical Physics [Waterloo], Centro Interdipartimentale Galvani (CIG), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of Bologna, Department of Physics, CAPRI M, SCARCELLA E, FUMELLI C, BIANCHI E, SALVIOLI S, MESIRCA P, AGOSTINI C, ANTOLINI A, SCHIAVONI A, CASTELLANI G., BERSANI F, and FRANCESCHI C.

Subjects
Adult, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Biophysics, Apoptosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, In Vitro Techniques, Peripheral blood mononuclear cell, Membrane Potentials, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, Humans, Radiology, Nuclear Medicine and imaging, Lymphocytes, 030304 developmental biology, Membrane potential, 0303 health sciences, Radiation, Specific absorption rate, Phosphatidylserine, Cell cycle, In vitro, Cell biology, Mitochondria, chemistry, 030220 oncology & carcinogenesis, Immunology, Cell Division
Abstract

International audience; The aim of this study was to investigate the nonthermal effects of radiofrequency (RF) fields on human immune cells exposed to a Global System for Mobile Communication (GSM) signal generated by a commercial cellular phone and by a sinusoidal non-modulated signal. To assess whether mobile phone RF-field exposure affects human immune cell functions, peripheral blood mononuclear cells (PBMCs) from healthy donors were exposed in vitro to a 900 MHz GSM or continuous-wave (CW) RF field 1 h/day for 3 days in a transverse electromagnetic mode (TEM) cell system (70-76 mW/kg average specific absorption rate, SAR). The cells were cultured for 48 or 72 h, and the following end points were studied: (1) mitogen-induced proliferation; (2) cell cycle progression; (3) spontaneous and 2-deoxy-D-ribose (dRib)-induced apoptosis; (4) mitochondrial membrane potential modifications during spontaneous and dRib-induced-apoptosis. Data obtained from cells exposed to a GSM-modulated RF field showed a slight decrease in cell proliferation when PBMCs were stimulated with the lowest mitogen concentration and a slight increase in the number of cells with altered distribution of phosphatidylserine across the membrane. On the other hand, cell cycle phases, mitochondrial membrane potential and susceptibility to apoptosis were found to be unaffected by the RF field. When cells were exposed to a CW RF field, no significant modifications were observed in comparison with sham-exposed cells for all the end points investigated.

Published
2004
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7. Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains.

Author

Kananen L, Enroth L, Raitanen J, Jylhävä J, Bürkle A, Moreno-Villanueva M, Bernhardt J, Toussaint O, Grubeck-Loebenstein B, Malavolta M, Basso A, Piacenza F, Collino S, Gonos ES, Sikora E, Gradinaru D, Jansen EHJM, Dollé MET, Salmon M, Stuetz W, Weber D, Grune T, Breusing N, Simm A, Capri M, Franceschi C, Slagboom PE, Talbot DCS, Libert C, Koskinen S, Bruunsgaard H, Hansen ÅM, Lund R, Hurme M, and Jylhä M

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Young Adult, Biomarkers blood, Biomarkers urine, Diagnostic Self Evaluation, Health Status, Self Report
Abstract

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

Published
2021
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8. Medication Intake Is Associated with Lower Plasma Carotenoids and Higher Fat-Soluble Vitamins in the Cross-Sectional MARK-AGE Study in Older Individuals.

Author

Weber D, Kochlik B, Stuetz W, Dollé MET, Jansen EHJM, Grubeck-Loebenstein B, Debacq-Chainiaux F, Bernhardt J, Gonos ES, Capri M, Franceschi C, Sikora E, Moreno-Villanueva M, Bürkle A, and Grune T

Abstract

The regular use of medication may interfere with micronutrient metabolism on several levels, such as absorption, turnover rate, and tissue distribution, and this might be amplified during aging. This study evaluates the impact of self-reported medication intake on plasma micronutrients in the MARK-AGE Project, a cross-sectional observational study in 2217 subjects (age- and sex-stratified) aged 35-75 years from six European countries that were grouped according to age. Polypharmacy as possible determinant of micronutrient concentrations was assessed using multiple linear regression models adjusted for age-group, dietary fruit, vegetables, and juice intake, and other confounders. Younger participants reported taking fewer drugs than older participants. Inverse associations between medication intake and lutein (-3.31% difference per increase in medication group), β-carotene (-11.44%), α-carotene (-8.50%) and positive associations with retinol (+2.26%), α-tocopherol/cholesterol (+2.89%) and γ-tocopherol/cholesterol (+1.36%) occurred in multiple adjusted regression models. Combined usage of a higher number of medical drugs was associated with poorer status of carotenoids on the one hand and higher plasma concentrations of retinol, α- and γ-tocopherol on the other hand. Our results raise concerns regarding the safety of drug combinations via the significant and surprisingly multifaceted disturbance of the concentrations of relevant micronutrients.

Published
2020
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9. MARK-AGE biomarkers of ageing.

Author

Bürkle A, Moreno-Villanueva M, Bernhard J, Blasco M, Zondag G, Hoeijmakers JH, Toussaint O, Grubeck-Loebenstein B, Mocchegiani E, Collino S, Gonos ES, Sikora E, Gradinaru D, Dollé M, Salmon M, Kristensen P, Griffiths HR, Libert C, Grune T, Breusing N, Simm A, Franceschi C, Capri M, Talbot D, Caiafa P, Friguet B, Slagboom PE, Hervonen A, Hurme M, and Aspinall R

Subjects
European Union, Female, Humans, Male, Aging metabolism, Biomarkers metabolism
Abstract

Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Published
2015
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10. Age-dependent effects of in vitro radiofrequency exposure (mobile phone) on CD95+ T helper human lymphocytes.

Author

Capri M, Salvioli S, Altilia S, Sevini F, Remondini D, Mesirca P, Bersani F, Monti D, and Franceschi C

Subjects
Adult, Aged, 80 and over, CD4-Positive T-Lymphocytes radiation effects, Cells, Cultured, Gene Expression Regulation radiation effects, Humans, Leukocytes, Mononuclear cytology, Lymphocyte Activation radiation effects, Aging radiation effects, Cell Phone, Radio Waves, T-Lymphocytes, Helper-Inducer radiation effects, fas Receptor radiation effects
Abstract

Recent studies on "nonthermal" effects of mobile phone radiofrequency (RF) suggest that RF can interact with cellular functions and molecular pathways. To study the possible RF effects on human lymphocyte activation, we analyzed CD25, CD95, CD28 molecules in unstimulated and stimulated CD4+ e CD8+ T cells in vitro. Peripheral blood mononuclear cells (PBMCs) from young and elderly donors were exposed or sham-exposed to RF (1,800 MHz, Specific Absorption Rate 2 W/kg) with or without mitogenic stimulation. No significant changes in the percentage of these cell subsets were found between exposed and sham-exposed lymphocytes in both young and elderly donors. Nevertheless, after RF exposure we observed a slight, but significant, downregulation of CD95 expression in stimulated CD4+ T lymphocytes from elderly, but not from young donors. This age-related result is noteworthy given the importance of a such molecule in regulation of the immune response.

Published
2006
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