Aging in the lympho-hematopoietic stem cell compartment

Cells of the immune system are progeny of a single primitive cell type, the hematopoietic stem cell (HSC). Aging in most strains of mice is associated with a reduction in HSC frequency and a reduction in HSC function. Aged HSCs demonstrate reduced differentiation toward the lymphoid lineage, and this might be a relevant factor influencing immunosenescence. The molecular mechanisms of HSC aging need to be determined in more detail, but current studies have identified, among others, a role for telomere dysfunction in inducing cell intrinsic checkpoints and environmental alterations, which both skews and reduces stem cell differentiation and function. Reverting or ameliorating aging of HSCs might be a crucial step to restoring immuno-competence in the elderly.