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

Cancer Immunology, Immunotherapy volume 58, pages 1909–1917 (2009)Cite this article

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.

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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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Authors and Affiliations

  1. Department of Experimental Pathology, University of Bologna, via S. Giacomo 12, 40126, Bologna, Italy

    Stefano Salvioli, Miriam Capri, Laura Bucci & Claudio Franceschi

  2. Interdepartmental Centre “L. Galvani” (C.I.G.), via S. Giacomo 12, 40126, Bologna, Italy

    Stefano Salvioli, Miriam Capri & Claudio Franceschi

  3. ER-GenTech Laboratory, via Saragat 1, 44100, Ferrara, Italy

    Stefano Salvioli & Claudio Franceschi

  4. Department of Experimental and Applied Pharmacology, Centre of Excellence in Applied Biology, University of Pavia, v.le Taramelli 14, 27100, Pavia, Italy

    Cristina Lanni, Marco Racchi & Stefano Govoni

  5. Department of Biomedical Sciences and Biotechnologies, University of Brescia, v.le Europa 11, 25123, Brescia, Italy

    Daniela Uberti & Maurizio Memo

  6. Department of Medical Sciences, Geriatrics Unit, University of Milan and IRCCS Istituto Auxologico Italiano, via Mosè Bianchi 90, 20149, Milan, Italy

    Daniela Mari

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  1. Stefano Salvioli
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Correspondence to Stefano Salvioli.

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This article is part of the Symposium in Writing on “Impact of Ageing on Cancer Immunity and Immunotherapy”.

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Salvioli, S., Capri, M., Bucci, L. et al. Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53. Cancer Immunol Immunother 58, 1909–1917 (2009). https://doi.org/10.1007/s00262-008-0639-6

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