Why adult stem cell functionality declines with age? Studies from the fruit fly Drosophila melanogaster model organism

Abstract

Highly regenerative adult tissues are supported by rare populations of stem cells that continuously divide to self-renew and generate differentiated progeny. This process is tightly regulated by signals emanating from surrounding cells to fulfill the dynamic demands of the tissue. One of the hallmarks of aging is slow and aberrant tissue regeneration due to deteriorated function of stem and supporting cells. Several Drosophila regenerative tissues are unique in that they provide exact identification of stem and neighboring cells in whole-tissue anatomy. This allows for precise tracking of age-related changes as well as their targeted manipulation within the tissue. In this review we present the stem cell niche of Drosophila testis, ovary and intestine and describe the major changes and phenotypes that occur in the course of aging. Specifically we discuss changes in both intrinsic properties of stem cells and their microenvironment that contribute to the decline in tissue functionality. Understanding these mechanisms in adult Drosophila tissues will likely provide new paradigms in the field of aging.

Keywords: Adult stem cells; Aging; Drosophila.; Niche.

Fig. (1)

Adult regeneration models in Drosophila. A) The male germline stem cell (GSC) niche is located at the apical tip of the testis. Three representative GSCs (of ~eight) intermingle with cyst stem cells (CySCs) to surround and contact the hub. The centrosomes (depicted by white dots) of the right GSC are aligned perpendicularly to the hub. The progenitor gonialblast (Gb) cell, which is encapsulated by two cyst cells, transiently amplifies (TA) four times prior to terminal differentiation. B) The female GSC niche is located at the tip of the germarium. Anteriorly, terminal filament cells (white) and cap cells form the somatic niche. Two GSCs are bound to the cap cells. The progenitor cystoblast (Cb) undergoes four mitotic divisions. Two follicle stem cells (FSCs) are located in the middle of the germarium. C) The intestinal stem cell (ISC) of the posterior midgut differentiates into a progenitor enteroblast (EB) that further differentiates either into a big enterocyte (EC) absorptive cell or to enteroendocrine (EE) secretory cell. Visceral muscle (VM); basal lamina (BL); peritrophic membrane (PM).