Centenarian offspring has a tighter control of Zn homeostasis which is likely to provide them constant protection against stress stimuli over the whole lifespan  [29.05.18]

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Original Study

Giacconi R¹, Costarelli L¹, Piacenza F¹, Basso A¹, Bürkle A², Moreno-Villanueva M², Grune T^3,4, Weber D^3,4, Stuetz W⁵, Gonos ES⁶, Schön C⁷, Grubeck-Loebenstein B⁸, Sikora E⁹, Toussaint O¹⁰, Debacq-Chainiaux F¹⁰, Franceschi C¹¹, Hervonen A¹², Slagboom E¹³, Ciccarone F¹⁴, Zampieri M^15,16, Caiafa P^15,16, Jansen E¹⁷, Dollé MET¹⁷, Breusing N^{https://www.researchgate.net/profile/Nicolle_Breusing18}, Mocchegiani E¹, Malavolta M¹. (2018) Zinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project. J Gerontol A Biol Sci Med Sci. 2018 May 9;73(6):745-753. doi: 10.1093/gerona/glx192

Author's information:

1. Translational Research Center of Nutrition and Ageing, IRCCS-INRCA, Ancona, Italy.
2. Molecular Toxicology Group, Department of Biology, University of Konstanz, Germany.
3. Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
4. NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany.
5. Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.
6. Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
7. BioTeSys GmbH, Esslingen, Germany.
8. Research Institute for Biomedical Aging Research, University of Innsbruck, Austria.
9. Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
10. URBC-NARILIS, University of Namur, Belgium.
11. CIG-Interdepartmental Center "L. Galvani", Alma Mater Studiorum, University of Bologna, Italy.
12. Medical School, University of Tampere, Finland.
13. Department of Molecular Epidemiology, Leiden University Medical Centre, The Netherlands.
14. Department of Biology, University of Rome "Tor Vergata", Italy.
15. Department of Cellular Biotechnologies and Hematology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Italy.
16. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
17. Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
18. Department of Applied Nutritional Science/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.

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.

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