**Hematopoietic Stem Cells in Aging and Disease**

244 Advances in Hematopoietic Stem Cell Research

Zhang, X. B., Beard, B. C., Trobridge, G. D., Wood, B. L., Sale, G. E., Sud, R., Humphries,

Zhao, C., Blum, J., Chen, A., Kwon, H. Y., Jung, S. H., Cook, J. M., Lagoo, A. & Reya, T.

1510.

Cancer Cell *12*, 528-541.

R. K. & Kiem, H. P. (2008b). *High incidence of leukemia in large animals after stem cell gene therapy with a HOXB4-expressing retroviral vector.* J Clin Invest *118*, 1502-

(2007). *Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo.* 

**11** 

*Spain* 

**Insights Into Stem Cell Aging** 

*Carlos III. (CNIC), Madrid,* 

A. Herrera-Merchan, I. Hidalgo, L. Arranz and S. Gonzalez

*Stem Cell Aging Group, Foundation Spanish National Cardiovascular Research Centre* 

The increase in average life expectancy in many developed countries is generating an aging society and an associated increase in age-related health problems. Mammalian aging occurs in part because of a decline in the restorative capacity of tissue stem cells. The use of stem cells in regenerative medicine promises to revolutionize the treatment of acute and chronic degenerative conditions, and stem cell research holds the key to the development of such therapies. The hallmark of adult stem cells is their ability to both self-renew and differentiate into multiple lineages. This demands a complex and still poorly understood network of molecular interactions between diverse cell-intrinsic regulators of self-renewal, such as certain Polycomb proteins and the tumor suppressor p16INK4a, both of which are absolutely required for the maintenance of certain stem cell population. Recent studies have begun to elucidate the molecular mechanisms underlying how stem cells decide between

Recent advances in medicine research programs, and a better health care planning, have great influences in people living in many Western countries, increasing both quality of life and average lifespan. With the extension of lifetime, there is increasing interest in slowing or reversing the negative effects of aging. The fascinating discovery of tissue-resident adult stem and progenitor cells in recent years has led to an explosion of interest in the development of novel stem cell-based therapies to improve endogenous regenerative

A major function of stem cells and their differentiation hierarchies may be to preserve the DNA integrity of the whole organism. When mutations occur despite certain errorprevention capacities, potent tumor-suppressor mechanisms such as senescence and apoptosis eliminate the damaged stem cell, limiting its replicative expansion. However, when unrepaired genetic lesions in stem cells are passed on to their differentiated daughters, and accumulate with aging, it is required replacement of dead and nonfunctional cells with newly differentiated cells derived from stem- and progenitor-cells. To date, the best-studied adult tissue stem cell type is the hematopoietic stem cell (HSC), which gives rise to all of the mature blood cells, throughout the life of the organism. Hematopoiesis in mammals occurs in distinct temporal waves shifting from the

life and death, and highlight the importance of balance in their aging pathways.

**1. Introduction** 

**2. Aging and stem cells** 

capacity or to repair damaged and diseased tissues.
