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


OBJECTIVE
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-beta, 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.
Salvioli
Stefano
S
Department of Experimental Pathology, University of Bologna, Bologna, Italy. stefano.salvioli@unibo.it
Capri
Miriam
M
Bucci
Laura
L
Lanni
Cristina
C
Racchi
Marco
M
Uberti
Daniela
D
Memo
Maurizio
M
Mari
Daniela
D
Govoni
Stefano
S
Franceschi
Claudio
C
D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I