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

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

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.

langue originaleAnglais
Pages (de - à)745-753
Nombre de pages9
journalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume73
Numéro de publication6
Les DOIs
étatPublié - 9 mai 2018

Empreinte digitale

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

Citer ceci

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. Dans: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2018 ; Vol 73, Numéro 6. p. 745-753.
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title = "Zinc-Induced Metallothionein in Centenarian Offspring from a Large European Population: The MARK-AGE Project",
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.",
keywords = "Aging, Longevity, Metallothionein, Senescence, Zinc",
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",
year = "2018",
month = "5",
day = "9",
doi = "10.1093/gerona/glx192",
language = "English",
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journal = "The Journals of Gerontology series A",
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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 2018, '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, VOL. 73, Numéro 6, p. 745-753. https://doi.org/10.1093/gerona/glx192

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.

Dans: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol 73, Numéro 6, 09.05.2018, p. 745-753.

Résultats de recherche: Contribution à un journal/une revueArticle

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

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

VL - 73

SP - 745

EP - 753

JO - The Journals of Gerontology series A

JF - The Journals of Gerontology series A

SN - 1079-5006

IS - 6

ER -