Effects of Hemocytes and Hemocyte Signaling on Longevity in Drosophila

In flies, hemocytes are universal immune cells that circulate in the hemolymph and participate in cellular and humoral immune responses. In this work, we used hemocyte-specific Hml driver to affect properties of hemocytes in adult flies. Expression of proapoptotic gene rpr resulted in a ten-fold reduction of hemocyte counts without causing apparent adverse effects on flies. Unexpectedly, the experimental flies with depleted hemocytes lived substantially longer then their control counterparts. An alternative approach to reduce hemocyte amounts by knocking down expression of anti-apoptotic gene Rbf1 also resulted in lifespan extension. Although in this case the lifespan extension was less profound, it was in a good agreement with the lesser extent of hemocyte count reduction. Conversely, expression of constitutively activated oncogene mutant RasV12 (but not dominant-negative mutant RasN17) moderately increased hemocyte counts and shortened lifespan of the experimental flies. Collectively, our data strongly suggest that the amount of hemocytes in adult flies inversely correlates with their longevity. In order to probe for the molecular mechanism that enables hemocytes to affect longevity, we addressed the central molecule in hemocyte humoral immune signaling - Rel (Drosophila homolog of NF-kB). Experimental flies with hemocyte-specific knockdown of the Rel gene demonstrated an extension in their lifespan. Consecutively, when hemocytes expressed the activated truncated form of Rel (Rel68), it shortened the lifespan of flies. We conclude that Rel plays a role in hemocyte-dependent longevity, potentially via stimulating expression of secretory peptides. Our study adds up to the growing evidence that the immune system plays a significant role in longevity