Dietary restriction enhances germline stem cell maintenance

Abstract

Dietary restriction (DR) increases lifespan in species ranging from yeast to primates, maintaining tissues in a youthful state and delaying reproductive senescence. However, little is known about the mechanisms by which this occurs. Here we demonstrate that, concurrent with extending lifespan, DR attenuates the age-related decline in male germline stem cell (GSC) number in Drosophila. These data support a model whereby DR enhances maintenance of GSCs to extend the reproductive period of animals subjected to adverse nutritional conditions. This represents the first example of DR maintaining an adult stem cell pool and suggests a potential mechanism by which DR might delay aging in the tissues of higher organisms.

Figure 1. DR extends lifespan in Drosophila males and increases average number of germline stem cells

(A) Schematic of the apical tip of the Drosophila testis (B) Lifespan of wild-type Drosophila males on fully fed (FF) or DR feeding paradigms. DR significantly extends lifespan of male flies (P<0.0001, Log Rank Test). Median Lifespan; Control = 57 days, DR = 66 days, 16% extension. Average number of GSCs per testis is shown (for time points indicated by dashed vertical lines) with standard error and number of testes analysed in parentheses. Significant increases in average number of GSCs per testis were observed in DR males compared to controls (Students T-test, asterisk p<0.05, double asterisk p<0.01). (C, D) Immunofluorescent images of testes from FF males (C) or males on DR feeding paradigm (D) stained with antibodies against Vasa (germ cells; green) and FasIII (hub; red). GSCs were scored as Vasa⁺ cells in contact with the hub (dots). Scale bars, 20 μm.

Figure 2. DR delays the rate of GSC loss with age

Combined average GSC number per testes in fully-fed (FF) and dietary restricted (DR) animals with age in three experiments. Linear regression for FF (blue, R² = 0.95) and DR (red, R² = 0.96) data points. DR significantly reduces the rate of GSC loss with age, analysis of covariance (ANCOVA) P=0.037, F=5.39.