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 journalArticlepeer-review

1 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)745-753
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume73
Issue number6
DOIs
Publication statusPublished - 9 May 2018

Keywords

  • Aging
  • Longevity
  • Metallothionein
  • Senescence
  • Zinc

Fingerprint Dive into the research topics of 'Zinc-Induced Metallothionein in Centenarian Offspring from a Large European Population: The MARK-AGE Project'. Together they form a unique fingerprint.

Cite this