Lymphopoiesis in the young (left) is characterized by robust B and T cell production in the bone marrow and thymus. The pool of HSCs includes a relatively high number of lymphoid-biased stem cells that efficiently generate lymphoid progenitors with high proliferative potential. However, with increasing age (right), the number of lymphoid-biased HSCs declines and myeloid-biased stem cells predominate, contributing to the reduced numbers of lymphoid progenitors. In addition, B cell progenitors in the bone marrow and T cell progenitors in the thymus exhibit reduced rates of proliferation and higher levels of apoptosis compared with their young counterparts. The increased expression of Ink4a and Arf in pro-B cells and Ink4a in ETPs contribute to this decreased proliferation/increased apoptosis. The decline in primary lymphopoiesis in turn results in a reduced number of naive cells that migrate to secondary lymphoid tissues such as the spleen.