Natural aging affects the clonal diversity within the primitive compartment as well as the clones that contribute to differentiation. Young Confetti-labeled HSCs and multipotent progenitors within the most primitive compartment (LSK) give rise to myeloid and lymphoid cells in a balanced output, with significant clonal diversity contributing to the differentiated cells. By mid-age, the number of LSK cells increases, but the overall clonal diversity begins to wane and there are changes in the clones contributing to differentiation. By 26 months, there is a large expansion of the LSK compartment with even greater loss of clonal diversity. Clonal contribution to the myeloid and lymphoid lineages is decreased but does not reflect the clonal distribution shifts in the LSK compartment, suggesting that many LSK cells may be unable to significantly contribute to downstream hematopoiesis. This loss of potential is also correlated with accumulation of clones that have acquired somatic mutations (represented by different colored cell borders).