Fig. 2.

Aging is associated with stem cell intrinsic alterations in lineage and progenitor potential. (A) Multilineage reconstitution (Left) and lineage potential (Right) from transplant experiments of LT-HSCs from young or old mice. Fifty KLSflk2-CD34- cells purified from young or old CD45.2 donors were transplanted into congenic (CD45.1) young recipients against 3 × 10⁵ competitor cells. Peripheral blood analysis was done at the indicated time points, and donor repopulating ability is presented as the percent of total white blood cells. Donor contribution to lymphoid and myeloid lineages is presented as the percent of B, myeloid, and T cells. (B) Aged BM microenvironment does not affect the lineage distribution of adoptively transferred LT-HSCs long term. Ninety LT-HSCs from young mice were transplanted into congenic young or old recipients along with 3 × 10⁵ competitor BM cells from old donors. Peripheral blood analysis was done at the indicated time points, and donor-derived contribution to B cells and myeloid cells is presented as the percent of T cell receptor (TCR) β-negative cells so as not to bias the B cell and myeloid cell data by negating the contribution of the involuted thymus in the old recipients. The contribution to T cells was looked at separately by gating on total donor-derived contribution to all lineages before assessing T cell contribution (Right). (C) BM frequencies of CMPs, GMPs, and MEPs from young (n = 10) and old mice (n = 9). (D) BM frequencies of CLP in young (n = 8), middle-aged (n = 5), and old mice (n = 7). (E) BM frequencies of donor-derived myeloid progenitors from either young or old donors into young recipient mice 4 months posttransplant (n = 4 young, n = 3 old). (F) BM frequencies of donor-derived CLPs from either young or old donors into young recipient mice 4 months posttransplant (young n = 9, old n = 4). Statistically significant differences are indicated by ^*; ^** indicates statistical significance to both age groups.