Cancer Immunology, Immunotherapy

, Volume 58, Issue 12, pp 1909–1917 | Cite as

Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53

  • Stefano Salvioli
  • Miriam Capri
  • Laura Bucci
  • Cristina Lanni
  • Marco Racchi
  • Daniela Uberti
  • Maurizio Memo
  • Daniela Mari
  • Stefano Govoni
  • Claudio Franceschi
Symposium in Writing

Abstract

Background

Centenarians are exceptionally long living individuals who escaped the most common age-related diseases. In particular they appear to be effectively protected from cancers. The mechanisms that underlie this protection are quite complex and still largely unclear.

Aim

To critically analyse the literature in order to propose a unifying hypothesis that can account for this cancer protection in centenarians.

Methods

Review of the scientific literature regarding three main players in tumourigenesis such as IGF-1, inflammation and p53, and centenarians.

Results

Centenarians appear to be characterised by low IGF-1-mediated responses and high levels of anti-inflammatory cytokines such as IL-10 and TGF-β, a condition that results in protection from cancer. Both inflammation and IGF-1 pathway converge on the tumour suppressor p53. Accordingly, some studies indicate that genetic variants of p53 are associated with human longevity by providing protection from cancer mortality.

Conclusions

The available data let us to hypothesise that among other possible mechanisms, well-preserved p53-mediated responses are likely a key factor contributing to protection from cancer in centenarians.

Keywords

Centenarians Cancer p53 IGF-1 Inflammation 

Notes

Acknowledgments

This work was supported by: EU (European Union) Grant “PROTEOMAGE” Contract n. FP6-518230; the PRRIITT program of the Emilia-Romagna Region (and Fondi Strutturali Obiettivo 2); Italian Ministry of Health Grant “Progetto Finalizzato «Studio delle differenze uomo-donna nei meccanismi patogenetici delle malattie cardiovascolari»” to C. Franceschi; Italian Ministry of University and Research (MiUR) PRIN 2006 Project to C. Franceschi (no. 2006061707), and S. Salvioli (no. 2006063387); University of Bologna Grant “Ricerca Fondamentale Orientata (RFO ex 60%) 2005”; Roberto and Cornelia Pallotti Legacy for Cancer Research Grants to C. Franceschi and S. Salvioli. University of Bologna “Progetti Strategici” 2006 grant (“p53 e patologie non neoplastiche nell’anziano: uno studio multidisciplinare sul ruolo del polimorfismo al codone 72 del gene TP53”) to S. Salvioli.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Stefano Salvioli
    • 1
    • 2
    • 3
  • Miriam Capri
    • 1
    • 2
  • Laura Bucci
    • 1
  • Cristina Lanni
    • 4
  • Marco Racchi
    • 4
  • Daniela Uberti
    • 5
  • Maurizio Memo
    • 5
  • Daniela Mari
    • 6
  • Stefano Govoni
    • 4
  • Claudio Franceschi
    • 1
    • 2
    • 3
  1. 1.Department of Experimental PathologyUniversity of BolognaBolognaItaly
  2. 2.Interdepartmental Centre “L. Galvani” (C.I.G.)BolognaItaly
  3. 3.ER-GenTech LaboratoryFerraraItaly
  4. 4.Department of Experimental and Applied Pharmacology, Centre of Excellence in Applied BiologyUniversity of PaviaPaviaItaly
  5. 5.Department of Biomedical Sciences and BiotechnologiesUniversity of BresciaBresciaItaly
  6. 6.Department of Medical Sciences, Geriatrics UnitUniversity of Milan and IRCCS Istituto Auxologico ItalianoMilanItaly

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