Abstract: Described herein are compositions and methods for reducing, improving, abrogating, or alleviating age- or aging-related functional decline in an older or aging subject by reducing the ratio or number of hematopoietic stem cells (HSCs) expressing high levels of the glycoprotein CD150 (CD150high HSCs), which may be dysfunctional or defective, in the subject. The methods involve reducing or removing dysfunctional or defective high CD150high HSCs from a sample obtained from a subject. Methods for administering to an old, aged, or aging subject having CD150high HSCs a composition comprising hematopoietic stem cells expressing low levels of the glycoprotein CD150 (CD150lowHSCs) or reducing or removing CD150high HSCs with an antibody-drug conjugate provide therapeutics that rejuvenate the differentiated hematopoietic cell types in the blood as well as improve the physical health of the aging subject to counter functional decline that occurs in aging HSCs.