Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Dis Model Mech. 2023 Apr 1;16(4). doi: 10.1242/dmm.049965. Epub 2023 Apr 26.
Antimicrobial peptides (AMPs) are innate immune effectors first studied for their role in host defence. 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 displayed reduced lifespan. Increased bacterial load in the food of aged ΔAMP14 flies suggested that their lifespan reduction was due to microbiome dysbiosis, consistent with a previous study. Moreover, germ-free conditions extended the lifespan of ΔAMP14 flies. Overall, our results did not point to an overt role of individual AMPs in lifespan. Instead, we found that AMPs collectively impact lifespan by preventing dysbiosis during aging.
抗菌肽（AMPs）是先天免疫效应物，最初因其在宿主防御中的作用而被研究。最近的研究表明，这些肽在清除异常细胞和神经退行性综合征中起作用。在果蝇中，许多 AMPs 在感染 Toll 和 Imd NF-κB 途径后被产生。随着年龄的增长，AMPs 被上调，这些分子作为与年龄相关的炎症性疾病的可能原因引起了人们的关注。然而，过表达或沉默这些基因的功能研究尚无定论。我们使用一组同源的 AMP 基因缺失系，研究了 AMPs 对衰老的净影响。总的来说，我们没有发现单个 AMP 对寿命有重大影响，除了防御素。然而，缺乏七个 AMP 基因家族的 ΔAMP14 果蝇显示出寿命缩短。老龄 ΔAMP14 果蝇的食物中细菌负荷增加表明，它们的寿命缩短是由于微生物组失调所致，这与之前的一项研究一致。此外，无菌条件延长了 ΔAMP14 果蝇的寿命。总的来说，我们的结果并没有指出单个 AMPs 在寿命方面的明显作用。相反，我们发现 AMPs 通过在衰老过程中防止微生物组失调来共同影响寿命。
