Dynamics of the male germline stem cell population during aging of Drosophila melanogaster

Abstract

SummaryDrosophila melanogaster has emerged as an important model system for the study of both stem cell biology and aging. Much is known about how molecular signals from the somatic niche regulate adult stem cells in the germline, and a variety of environmental factors as well as single point mutations have been shown to affect lifespan. Relatively little is known, however, about how aging affects specific populations of cells, particularly adult stem cells that may be susceptible to aging-related damage. Here we show that male germline stem cells (GSCs) are lost from the stem cell niche during aging, but are efficiently replaced to maintain overall stem cell number. We also find that the division rate of GSCs slows significantly during aging, and that this slowing correlates with a reduction in the number of somatic hub cells that contribute to the stem cell niche. Interestingly, slowing of stem cell division rate was not observed in long-lived methuselah mutant flies. We finally investigated whether two mechanisms that are thought to be used in other adult stem cell types to minimize the effects of aging were operative in this system. First, in many adult tissues stem cells exhibit markedly fewer cell cycles relative to transit-amplifying cells, presumably protecting the stem cell pool from replication-associated damage. Second, at any given time not all stem cells actively cycle, leading to 'clonal succession' from the reserve pool of initially quiescent stem cells. We find that neither of these mechanisms is used in Drosophila male GSCs.

Age‐related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila

“…By analysis of BrdU labeling and of clone marking, there is about a threefold reduction of GSC division from day 3 to day 40. Significant changes of stem cell division rate have also been reported in male GSCs (Wallenfang et al, 2006). At least in females, the decline of GSC division rate is associated with impaired dpp niche signaling activity as revealed by two pathway activation markers, pMad and Dad-lacZ.…”

“…Because the half-life of GSC is 4.6 weeks (Xie & Spradling, 1998), maintenance of relative constant GSC number in the aged individuals is likely to result from stem cell replacement when the neighboring GSC undergoes symmetric division (Xie & Spradling, 2000;Zhu & Xie, 2003). Stem cell replacement also occurs in male GSC niche in Drosophila (Wallenfang et al, 2006), but it is not known whether the lost GSC is replaced by the expansion of the neighboring GSCs or by the dedifferentiation of progenitors (Brawley & Matunis, 2004;Kai & Spradling, 2004). Clonal expansion of the stem cell pool has been suggested to occur in mammals (Chenn & McConnell, 1995;Shinohara et al, 2002;Cao et al, 2004), suggesting that stem cell replacement could be a general mechanism to keep relative constant number of stem cells with age.…”

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

“…However, with advancing age, the numerous replications of the male germ-line also may exert a powerful selection pressure that yields stem cells, which survive the impact of aging. This has been shown in aging male Drosophila melanogaster in which the population of germ-line stem cells is only a subset of the original population at a younger age [41].…”

Tumors of the testis and midgut in aging flies

“…9 While most adult fly tissues lack mitotic activity the testes and gut are both capable of ongoing stem cell proliferation into adult life. [10][11][12] Such ongoing mitotic activity might make these early progenitor cells particularly susceptible to neoplastic transformation secondary to declines in the effectiveness of DNA repair. The morphologic similarity of the testis tumor cells to germ line stem cells is consistent with this possibility.…”