Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells.

Mammary gland aging is due to aberrant activation of p66Shc, which induces p53/p44 signaling, leading to failure of symmetric divisions, decreased proliferation and reduced regenerative potential of MaSCs. Age-related changes in mammary epithelial cells derived from C57BL/6J WT and p66Shc knockedout mice cultured as stem cell-enriched mammospheres. Overall design: Bulk RNA-sequencing analysis on total RNA extracted from passage 2 mammosferes derived from 3 young (2 month-old) and 3 aged (12 month-old) C57BL/6J WT and p66Shc knock-out (p66-/- C57BL/6J) mice.