Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing.

ABSTRACT: Mammalian ageing is associated with reduced regenerative capacity in tissues that contain stem cells. It has been proposed that this is at least partially caused by the senescence of progenitors with age; however, it has not yet been tested whether genes associated with senescence functionally contribute to physiological declines in progenitor activity. Here we show that progenitor proliferation in the subventricular zone and neurogenesis in the olfactory bulb, as well as multipotent progenitor frequency and self-renewal potential, all decline with age in the mouse forebrain. These declines in progenitor frequency and function correlate with increased expression of p16INK4a, which encodes a cyclin-dependent kinase inhibitor linked to senescence. Ageing p16INK4a-deficient mice showed a sign

SUBMITTER: Molofsky AV 

PROVIDER: S-EPMC2586960 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature