Aging of Intestinal Stem Cells in Drosophila Melanogaster

Drosophila m. has a long history of major contributions to basic biology and biomedical research. Not surprisingly, the recent identification of several multipotent stem cell populations in the Drosophila fly digestive tract has generated an immense enthu

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Aging of Intestinal Stem Cells in Drosophila Melanogaster Benoît Biteau

Abstract

Drosophila m. has a long history of major contributions to basic biology and biomedical research. Not surprisingly, the recent identification of several multipotent stem cell populations in the Drosophila fly digestive tract has generated an immense enthusiasm in the research community. This experimental model provides a unique opportunity to study adult somatic stem cells, using the power of fly genetics. Over the past few years, research in this field has focused on the characterization of the signaling pathways and mechanisms that control stem cell function and tissue repair in the intestine. Importantly, the rapid aging and short lifespan of Drosophila make this model ideal to investigate the impact of aging on stem cell populations and test the contribution of somatic stem cells to normal healthspan and lifespan. This chapter presents recent findings that elucidate the mechanisms causing age-related loss of tissue homeostasis in the fly intestine, as well as strategies of stem cell-specific genetic manipulation that significantly impact physiology in aging animals and can extend lifespan.

5.1

Introduction

With the identification of stem cell populations in the developing larval brain and the gonads, studies in Drosophila have been pivotal to the discovery of fundamental processes that regulate stem cell biology in many other stem/progenitor compartments. For example, many conserved mechanisms that control asymmetric cell division and cell specification were first identified in larval neuroblasts (Knoblich 2010), while studies of the germline stem cells in the fly testis and ovary B. Biteau Department of Biomedical Genetics, University of Rochester Medical Center, 633 Elmwood Avenue, Rochester, NY, USA e-mail: [email protected] © Springer-Verlag Wien 2015 H. Geiger et al. (eds.), Stem Cell Aging: Mechanisms, Consequences, Rejuvenation, DOI 10.1007/978-3-7091-1232-8_5

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lead to the first demonstration of the concept of stem cell niches (Decotto and Spradling 2005; Fuller and Spradling 2007). Although these models have significantly contributed to our understanding of stem cell biology, they provided only limited insight into the impact of aging on somatic multipotent stem cell populations and the influence of these progenitors on the maintenance of healthy tissues and normal longevity. The recent identification of multipotent stem cell populations in the fly gastrointestinal tract has revolutionized aging research in Drosophila. While previous studies had vastly focused on the mechanisms allowing the protection of somatic cells, the possibility that adult somatic cells are maintained by tissue-specific progenitors opened up new research avenues. Importantly, combined with the short lifespan and the power of fly genetics, this new experimental system provides a unique opportunity to directly address in vivo questions that were previously inaccessible. For example, what is the impact of aging on