TY - JOUR
T1 - Zinc-Induced Metallothionein in Centenarian Offspring from a Large European Population
T2 - The MARK-AGE Project
AU - Giacconi, Robertina
AU - Costarelli, Laura
AU - Piacenza, Francesco
AU - Basso, Andrea
AU - Bürkle, Alexander
AU - Moreno-Villanueva, Maria
AU - Grune, Tilman
AU - Weber, Daniela
AU - Stuetz, Wolfgang
AU - Gonos, Efstathios S.
AU - Schön, Christiane
AU - Grubeck-Loebenstein, Beatrix
AU - Sikora, Ewa
AU - Toussaint, Olivier
AU - Debacq-Chainiaux, Florence
AU - Franceschi, Claudio
AU - Hervonen, Antti
AU - Slagboom, Eline
AU - Ciccarone, Fabio
AU - Zampieri, Michele
AU - Caiafa, Paola
AU - Jansen, Eugène
AU - Dollé, Martijn E.T.
AU - Breusing, Nicolle
AU - Mocchegiani, Eugenio
AU - Malavolta, Marco
N1 - Funding Information:
1Translational Research Center of Nutrition and Ageing, IRCCS-INRCA, Ancona, Italy. 2Molecular Toxicology Group, Department of Biology, University of Konstanz, Germany. 3Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. 4NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany. 5Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany. 6Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece. 7BioTeSys GmbH, Esslingen, Germany. 8Research Institute for Biomedical Aging Research, University of Innsbruck, Austria. 9Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland. 10URBC-NARILIS, University of Namur, Belgium. 11CIG-Interdepartmental Center “L. Galvani”, Alma Mater Studiorum, University of Bologna, Italy. 12Medical School, University of Tampere, Finland. 13Department of Molecular Epidemiology, Leiden University Medical Centre, The Netherlands. 14Department of Biology, University of Rome “Tor Vergata”, Italy. 15Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Italy. 16Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy. 17Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. 18Department of Applied Nutritional Science/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Funding Information:
This work was supported by the European Union’s Seventh Framework Program (HEALTH-F4-2008–200880 MARK-AGE).
Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/5/9
Y1 - 2018/5/9
N2 - 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.
AB - 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.
KW - Aging
KW - Longevity
KW - Metallothionein
KW - Senescence
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=85047084567&partnerID=8YFLogxK
U2 - 10.1093/gerona/glx192
DO - 10.1093/gerona/glx192
M3 - Article
AN - SCOPUS:85047084567
SN - 1079-5006
VL - 73
SP - 745
EP - 753
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 6
ER -