Aging of hematopoietic stem cells:Intrinsic changes or micro-environmental effects?

During development hematopoietic stem cells (HSCs) expand in number and persist throughout life by undergoing self-renewing divisions. Nevertheless, the hematopoietic system does not escape the negative effects of aging, suggesting that self-renewal is not complete. A fundamental issue in stem cell biology relates to such age-dependent loss of stem cell activity. Both stem cell intrinsic factors and extrinsic factors associated with an aging micro-environment could contribute to aging of the hematopoietic system. Recently, changes in the clonal composition of the HSC compartment during aging have been put forward as a key factor. Here, we discuss these recent developments and speculate how they may be of clinical relevance.