Zinc-induced Metallothionein in centenarian offspring from a large European population: the MARK-AGE Project

Robertina Giacconi, Laura Costarelli, Francesco Piacenza, Andrea Basso, Alexander Bürkle, Maria Moreno-Villanueva, Tilman Grune, Daniela Weber, Wolfgang Stuetz, Efstathios S Gonos, Christiane Schön, Beatrix Grubeck-Loebenstein, Ewa Sikora, Olivier Toussaint, Florence Debacq-Chainiaux, Claudio Franceschi, Antti Hervonen, Eline Slagboom, Fabio Ciccarone, Michele ZampieriPaola Caiafa, Eugène Jansen, Martijn E T Dollé, Nicolle Breusing, Eugenio Mocchegiani, Marco Malavolta

Research output: Contribution to journalArticle

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 favourably influence longevity, although their role in human aging is not completely understood.Within the European multicenter study MARK-AGE, we analysed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2936 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.

Original languageEnglish
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
DOIs
Publication statusE-pub ahead of print - Oct 17 2017

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Metallothionein
Zinc
Population
Blood Cells
Homeostasis
Malondialdehyde
Spouses
Transgenic Mice
Multicenter Studies
Oxidation-Reduction
Cysteine
Blood Proteins
Oxidative Stress
Biomarkers
zinc thionein
Lymphocytes
Genes
Proteins
Therapeutics

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Zinc-induced Metallothionein in centenarian offspring from a large European population : the MARK-AGE Project. / Giacconi, Robertina; Costarelli, Laura; Piacenza, Francesco; Basso, Andrea; Bürkle, Alexander; Moreno-Villanueva, Maria; Grune, Tilman; Weber, Daniela; Stuetz, Wolfgang; Gonos, Efstathios S; Schön, Christiane; Grubeck-Loebenstein, Beatrix; Sikora, Ewa; Toussaint, Olivier; Debacq-Chainiaux, Florence; Franceschi, Claudio; Hervonen, Antti; Slagboom, Eline; Ciccarone, Fabio; Zampieri, Michele; Caiafa, Paola; Jansen, Eugène; Dollé, Martijn E T; Breusing, Nicolle; Mocchegiani, Eugenio; Malavolta, Marco.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 17.10.2017.

Research output: Contribution to journalArticle

Giacconi, R, Costarelli, L, Piacenza, F, Basso, A, Bürkle, A, Moreno-Villanueva, M, Grune, T, Weber, D, Stuetz, W, Gonos, ES, Schön, C, Grubeck-Loebenstein, B, Sikora, E, Toussaint, O, Debacq-Chainiaux, F, Franceschi, C, Hervonen, A, Slagboom, E, Ciccarone, F, Zampieri, M, Caiafa, P, Jansen, E, Dollé, MET, Breusing, N, Mocchegiani, E & Malavolta, M 2017, 'Zinc-induced Metallothionein in centenarian offspring from a large European population: the MARK-AGE Project', Journals of Gerontology - Series A Biological Sciences and Medical Sciences. https://doi.org/10.1093/gerona/glx192
Giacconi, Robertina ; Costarelli, Laura ; Piacenza, Francesco ; Basso, Andrea ; Bürkle, Alexander ; Moreno-Villanueva, Maria ; Grune, Tilman ; Weber, Daniela ; Stuetz, Wolfgang ; Gonos, Efstathios S ; Schön, Christiane ; Grubeck-Loebenstein, Beatrix ; Sikora, Ewa ; Toussaint, Olivier ; Debacq-Chainiaux, Florence ; Franceschi, Claudio ; Hervonen, Antti ; Slagboom, Eline ; Ciccarone, Fabio ; Zampieri, Michele ; Caiafa, Paola ; Jansen, Eugène ; Dollé, Martijn E T ; Breusing, Nicolle ; Mocchegiani, Eugenio ; Malavolta, Marco. / Zinc-induced Metallothionein in centenarian offspring from a large European population : the MARK-AGE Project. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2017.
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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 favourably influence longevity, although their role in human aging is not completely understood.Within the European multicenter study MARK-AGE, we analysed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2936 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.",
author = "Robertina Giacconi and Laura Costarelli and Francesco Piacenza and Andrea Basso and Alexander B{\"u}rkle and Maria Moreno-Villanueva and Tilman Grune and Daniela Weber and Wolfgang Stuetz and Gonos, {Efstathios S} and Christiane Sch{\"o}n and Beatrix Grubeck-Loebenstein and Ewa Sikora and Olivier Toussaint and Florence Debacq-Chainiaux and Claudio Franceschi and Antti Hervonen and Eline Slagboom and Fabio Ciccarone and Michele Zampieri and Paola Caiafa and Eug{\`e}ne Jansen and Doll{\'e}, {Martijn E T} and Nicolle Breusing and Eugenio Mocchegiani and Marco Malavolta",
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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 - © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2017/10/17

Y1 - 2017/10/17

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 favourably influence longevity, although their role in human aging is not completely understood.Within the European multicenter study MARK-AGE, we analysed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2936 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 favourably influence longevity, although their role in human aging is not completely understood.Within the European multicenter study MARK-AGE, we analysed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2936 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.

U2 - 10.1093/gerona/glx192

DO - 10.1093/gerona/glx192

M3 - Article

C2 - 29045571

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

ER -