Stem Cells

Although the molecular mechanisms of impaired organ maintenance during ageing are largely unknown, it has been recognized that impaired organ maintenance correlates with impaired function of adult stem cells during ageing. An understanding of molecular mechanisms that are responsible for adult stem cell ageing is of utmost importance to develop new therapies aiming to improve organ maintenance and function during ageing. The second part of this book focuses on adult stem cell ageing. Garry Van Zant and coworkers provide a summary of our current knowledge of ageing of hematopoietic stem cells. The authors describe age associated changes in stem cell number and function, and describe molecular pathways involved in stem cell ageing. Their chapter shows that both cell intrinsic checkpoints and environmental alterations represent major determinants limiting stem cell function during ageing. Stefan Zimmermann and Uwe Martens also focus on hematopoietic stem cell ageing.

The authors summarize evidence that both telomere-dependent and telomere-inde-pendent mechanisms can limit hematopoietic stem cell function in ageing mice and humans. Luis Gutierrez and Zhenyu Ju demonstrate that telomere dysfunction induces cell intrinsic checkpoints and environmental alterations that limit stem cell function in ageing telomerase-deficient mice. Norman E. Sharpless discusses the role of the cell cycle inhibitor p16 on stem cell function during ageing. It is still not entirely clear how the p16 and the Rb- checkpoint are linked to telomere dysfunction. Sharpless summarizes evidence indicating that p16 is upregulated during ageing and impairs the function of ageing stem cells in various compartments. He shows that p16 can be regulated by telomere-dependent and -independent mechanisms. Steven Artandi ends the section on stem cell ageing by reviewing the role of telomerase for stem cell function. He summarizes initial evidence that telomere-independent functions of telomerase can regulate adult stem cell function, and it will be interesting to explore these mechanisms in ageing stem cells.

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