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

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. To critically analyse the literature in order to propose a unifying hypothesis that can account for this cancer protection in centenarians. Review of the scientific literature regarding three main players in tumourigenesis such as IGF-1, inflammation and p53, and centenarians. 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. 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.