Failing to adapt – the ageing immune system's role in cancer pathogenesis

Abstract

Cancer incidence rates rise exponentially with age, previously considered to be due to increased exposure to mutagenic agents. Refined statistical analysis has, however, highlighted a plateau in cancer incidence rates amongst the general population post eighty-five years of age. This, coupled with the peak of numerous malignant pathologies during early or middle life, indicates a crucial role for other factors in controlling the timing and nature of cancer development. Immune function is known to decrease with age, indicating that increased chronic infection amongst the elderly may, in part, give rise to increased cancer incidence. Further, the chronic low grade inflammatory environment created as one ages may also initiate malignant neoplastic progression. Pro-inflammatory cytokines, such as TNF-alpha, Il-6 and prostaglandins (increased through TNF-alpha induced COX increases) increase during ageing and cause malignant transformation through inducing cellular proliferation, angiogenesis and the inhibition of apoptosis. This article will discuss these changes in detail and show that centenarians possess key polymorphisms, responsible for decreased TNF-α and IL-6 production amongst other changes, that act as survival advantages; protecting them from age-induced malignant neoplastic transformation. The need to transition to reviewing cancer as a disorder at the tissue, rather than cellular, level will thus be highlighted.