Ageing as developmental decay: insights from p16(INK4a.)

The p16 INK4a cell cycle regulator is one of the best ageing biomarkers because it is suppressed in early embryogenesis and progressively induced during ageing. p16 INK4a plays a crucial role in key cell fate decisions which contribute to ageing, such as cellular senescence and stem cell dynamics. Detailed examination of the pathways regulating p16 INK4a expression has revealed an overlap with those regulating early development. We present the hypothesis that ageing might be primarily driven by gradual functional decay of developmental pathways. To support this, we summarise the role of p16 INK4a in ageing and our current knowledge on p16 INK4a regulation. The developmental decay hypothesis implies that the much-evidenced damage associated with all aspects of ageing might be secondary to such decay.