Compositions and methods for assessing, treating, or reducing aging-related functional decline

A method of improving physical health and aging-related hematopoietic cell functional decline of a selected subject, the method comprising:

• selecting the subject by detecting hematopoietic stem cells (HSC) expressing high levels of CD150 polypeptide (CD150high HSCs) in a sample obtained from the subject;
• and
• administering to the subject an effective amount of hematopoietic stem cells (HSCs) expressing low levels of CD150 polypeptide (CD150low HSCs) or a composition thereof comprising a physiologically acceptable carrier, excipient or diluent;
• wherein the CD150low HSCs differentiate into hematopoietic cell types which improve physical health and aging-related hematopoietic cell functional decline in the subject.

Use of a composition comprising an effective amount of hematopoietic stem cells expressing a low abundance of the CD150 glycoprotein (CD150low HSCs), wherein said CD150low HSCs have a mean fluorescence intensity of less than about 4×103 cell surface expressed CD150 proteins per cell or wherein CD150low HSCs comprise the lowest 25% subpopulation of a Long-Term-HSC population which expresses a Lin−Sca-1+c-Kit+CD48-CD34−CD150+ cell surface biomarker signature based on flow cytometry or fluorescence activated cell sorting (FACS) analysis and/or express marker genes Rnase6 and Arhgap30, in the manufacture of a medicament for treating an aging or aged subject having hematopoietic stem cells expressing a high abundance of the CD150 glycoprotein (CD150high HSCs);

• wherein the CD150high HSCs have a mean fluorescence intensity of greater than about 4×103 cell surface expressed CD150 proteins per cell or wherein CD150high HSCs comprise the highest 25% subpopulation of a Long-Term-HSC population which expresses a Lin−Sca-1+c-Kit+CD48−CD34−CD150+ cell surface biomarker signature based on flow cytometry or fluorescence activated cell sorting (FACS) analysis;
• and/or
• wherein the CD150high HSCs express a CD150 mRNA level of between about 0.3 to about 2 RNA Units per cell;
• and/or
• wherein the CD150high HSCs express one or more age-related marker genes selected from the group consisting of Sbspon, Ehd3, Clu, Dpy19l2, Kcnb2, Selp, B3gnt8, Jam2, Enpp5, Gpr183, and Ramp2.

A method of reducing or eliminating dysfunctional or defective CD150-expressing hematopoietic stem cells (HSCs) in a subject, the method comprising:

• contacting a sample containing CD150-expressing hematopoietic stem cells (HSCs) obtained from a subject in need thereof with an anti-CD150 antibody conjugated to a cellular toxin in an amount effective to bind to high CD150-expressing HSCs (CD150high HSCs);
• wherein the CD150high HSCs express one or more age-related marker genes selected from the group consisting of Sbspon, Ehd3, Clu, Dpy19l2, Kcnb2, Selp, B3gnt8, Jam2, Enpp5, Gpr183, and Ramp2 which correlate with high expression of CD150 on the cell surface;
• culturing the sample for a time sufficient for the anti-CD150 antibody-toxin conjugate to cause cytolysis of the high CD150-expressing HSCs;
• and
• obtaining a sample in which dysfunctional or defective CD150-expressing hematopoietic stem cells (HSCs) are reduced or eliminated.