Antimicrobial peptides do not directly contribute to aging in Drosophila, but improve lifespan by preventing dysbiosis

Abstract

Antimicrobial peptides (AMPs) are innate immune effectors first studied for their role in host defense. Recent studies have implicated these peptides in the clearance of aberrant cells and in neurodegenerative syndromes. In Drosophila, many AMPs are produced downstream of Toll and Imd NF-κB pathways upon infection. Upon aging, AMPs are upregulated, drawing attention to these molecules as possible causes of age-associated inflammatory diseases. However, functional studies overexpressing or silencing these genes have been inconclusive. Using an isogenic set of AMP gene deletions, we investigated the net impact of AMPs on aging. Overall, we found no major effect of individual AMPs on lifespan, with the possible exception of Defensin. However, ΔAMP14 flies lacking seven AMP gene families display reduced lifespan. Increased bacterial load in the food of aged ΔAMP14 flies suggests their lifespan reduction is due to microbiome dysbiosis, consistent with a previous study. Moreover, germ-free conditions extends the lifespan of ΔAMP14 flies. Overall, our results do not point to an overt role of individual AMPs in lifespan. Instead, we find that AMPs collectively impact lifespan by preventing dysbiosis during aging.

Resistance to host antimicrobial peptides mediates resilience of gut commensals during infection and aging inDrosophila

“…6d). These results suggest that AMPs are responsible for controlling commensal load during aging, consistent with the findings of Hanson et al, 45 and that resistance to AMPs is essential for commensals persistence in the inflamed gut environment of aging flies.…”

“…The following Drosophila stocks used in this study were kindly provided by Dr. Bruno Lemaitre: DrosDel w 1118 iso; Relish E20 iso; ΔAMP iso; UAS-Relish ; UAS-CecA ; w;Myo1A-Gal4,tub-Gal80TS,UAS-GFP ; w;esg-Gal4,tub-Gal80TS,UAS-GFP 13 ,22, 45 . The following stocks were obtained from the Bloomington Drosophila Stock Center: w*; P{DptA-GFP.JM863}D3-2 P{DptA-GFP.JM863}3-4 (55709); UAS-mCD8::GFP (32185).…”

Naturally occurring viruses of Drosophila reduce offspring number and lifespan

“…Nevertheless, despite relatively small sample sizes, we found substantial reductions in longevity and offspring production in Drosophila naturally infected by several viruses. This is consistent with the scale of the mortality increase seen in larvae orally infected with DCV [63,64], with the lifespan reduction seen in some DmelNV infected Dmel stocks [28], with the fecundity reduction seen in susceptible Dmel orally infected with DAV [4], and in D. suzukii orally infected with Newfield virus [19]. Given the large effective population size of Drosophila species, such reductions in fitness-around several or even tens of per cent-could represent enormous selective pressures if translated to the wild.…”

The antimicrobial peptide database is 20 years old: Recent developments and future directions

“…This discovery won Jules Hoffmann a Nobel prize in 2011. This milestone discovery inspired the continued search of novel functional roles of these innate immune peptides in coat color, sleep and lifespan till today (Candille et al, 2007; Hanson & Lemaitre, 2023; Toda et al, 2019). The third phase was triggered by the applications of the proteomic and genomic technologies to AMP research.…”