Background: Centenarians are exceptionally long living individuals who escaped the most common age-related diseases. In particular they appear to be eVectively 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 scientiWc 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-inXammatory cytokines such as IL-10 and TGF-, a condition that results in protection from cancer. Both inXammation 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.
Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53.
LANNI, CRISTINA;RACCHI, MARCO;GOVONI, STEFANO;
2009-01-01
Abstract
Background: Centenarians are exceptionally long living individuals who escaped the most common age-related diseases. In particular they appear to be eVectively 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 scientiWc 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-inXammatory cytokines such as IL-10 and TGF-, a condition that results in protection from cancer. Both inXammation 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
