p16INK4a: A central player in cellular senescence and a promising aging biomarker in elderly cancer patients

The p16INK4a tumor suppressor protein functions as a cyclin-dependent kinase inhibitor, preventing phosphorylation of the retinoblastoma protein and consequently arresting the cell cycle in the G1-phase. Together with p53 and p21CIP1 it has an important function in inducing permanent cell cycle arrest, called senescence, in response to all sorts of cellular damage. Bypass of these senescence pathways has been shown to be associated with increased occurrence of multiple malignancies. In this review we focus on the role of p16INK4a in cellular senescence, its tumor suppression potential and its effect on aging. Also, the consequences of senescence in cancer therapy and its possible side-effects are considered. p16INK4a expression in peripheral blood T-lymphocytes is discussed as a promising candidate biomarker which could reflect biological age and could be used to guide individual optimal treatment in the elderly cancer population.