The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI-1 plasma levels in ageing

Roberto Testa, Anna Rita Bonfigli, Stefano Salvioli, Laura Invidia, Michela Pierini, Cristina Sirolla, Maurizio Marra, Ivano Testa, Francesca Fazioli, Rina Recchioni, Fiorella Marcheselli, Fabiola Olivieri, Luigi Lanari, Claudio Franceschi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Plasminogen activator inhibitor 1 (PAI-1) is over-expressed during ageing and it has been linked to cellular senescence. Recently, PAI-1 has been also identified in vitro as a critical downstream target of p53. TP53, the p53 gene, has a common functional polymorphism at codon 72 which influences the capability to modulate both apoptosis and cell senescence. In the attempt to demonstrate an in vivo role of p53 in the relationship between PAI-1 and age, we studied PAI-1 on 570 healthy subjects (aged from 18 to 92 yrs.). PAI-1 showed significant relationship with age (r = 0.12, p = 0.02). Stratifying by genotype, it became evident that the association between PAI-1 and age was mainly due to Pro/Pro subjects (partial r = 0.75, p <0.01). These results have been confirmed by a validation study on an independent sample population of 496 subjects (aged from 18 to 94 yrs.). This is the first demonstration of an in vivo role of TP53 polymorphism in PAI-1 regulation, supporting the hypothesis that the effects of this polymorphism are age-dependent. In particular, our results indicate that Pro/Pro genotype plays a pivotal role in determining PAI-1 levels in aged subjects, while in Arg carriers PAI-1 levels are associated to the known insulin related determinants.

Original languageEnglish
Pages (from-to)497-500
Number of pages4
JournalMechanisms of Ageing and Development
Volume130
Issue number8
DOIs
Publication statusPublished - Aug 2009

Fingerprint

Plasminogen Activator Inhibitor 1
Codon
Genotype
Cell Aging
p53 Genes
Validation Studies
Healthy Volunteers
Insulin
Apoptosis

Keywords

  • Ageing
  • Plasminogen activator inhibitor 1
  • TP53 codon 72 polymorphism

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology

Cite this

The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI-1 plasma levels in ageing. / Testa, Roberto; Bonfigli, Anna Rita; Salvioli, Stefano; Invidia, Laura; Pierini, Michela; Sirolla, Cristina; Marra, Maurizio; Testa, Ivano; Fazioli, Francesca; Recchioni, Rina; Marcheselli, Fiorella; Olivieri, Fabiola; Lanari, Luigi; Franceschi, Claudio.

In: Mechanisms of Ageing and Development, Vol. 130, No. 8, 08.2009, p. 497-500.

Research output: Contribution to journalArticle

Testa, Roberto ; Bonfigli, Anna Rita ; Salvioli, Stefano ; Invidia, Laura ; Pierini, Michela ; Sirolla, Cristina ; Marra, Maurizio ; Testa, Ivano ; Fazioli, Francesca ; Recchioni, Rina ; Marcheselli, Fiorella ; Olivieri, Fabiola ; Lanari, Luigi ; Franceschi, Claudio. / The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI-1 plasma levels in ageing. In: Mechanisms of Ageing and Development. 2009 ; Vol. 130, No. 8. pp. 497-500.
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