FIGURE 1. Dual activities of p16^INK4a during ageing.

Ageing causes an increase in p16^INK4a, a potent tumour suppressor that promotes longevity by suppressing the development of cancer. Three papers show that p16^INK4a suppresses the proliferation of stem or progenitor cells in the bone marrow, pancreas and brain^{3, 4, 5}. The mechanisms that induce p16^INK4a during ageing are not known (black box). Once expressed, p16^INK4a causes cellular senescence (grey box), a permanent growth-arrested state, which may be the mechanism by which this protein suppresses the proliferation of stem/progenitor cells. The decline in stem/progenitor-cell proliferation compromises tissue regeneration and repair, which is likely to reduce longevity.