Minocycline Extends Lifespan through Boosting NAD + levels, Reducing Inflammation, and Regulating Gut Microbiome Dynamics in Drosophila melanogaster

Abstract

<title>Abstract</title> Persistent DNA damage, and inflammageing contribute to the depletion of NAD⁺ which in turn exacerbates age-related diseases. Minocycline may combat ageing and related declines by targeting the FOXO and kynurenine (KYN) pathways. However, its impact on inflammageing, food intake, fecundity, NAD⁺ levels, and the gut milieu, remains unexplored. This study evaluated the lifespan extending property of minocycline in adult <italic>Drosophila melanogaster</italic>. Aged flies of both sexes, were divided into four groups. Group I, received distilled water, while groups II - IV received 0.05 mM, 0.10 mM, and 0.20 mM of minocycline, respectively, throughout life and until days 20 and 40. Life span, food intake and fecundity were determined in the flies. NAD⁺, NF-kB, NO and MTT, flies were assayed using ELISA kits and colorimetry. Smurf assay was done to assess intestinal barrier integrity and gut pH, while gut microbial load was determined by counting colony forming units (CFUs) per fly gut. Minocycline significantly (p &lt; 0.05) increased lifespan, gut pH, NAD⁺ levels and significantly reduced food intake, fecundity, NO, NF-kB, gut microbiota load and percentage barrier dysfunction in comparison to the control. Minocycline may extend lifespan by caloric restriction, preventing declines in NAD⁺, modulating of the gut environment and decreasing inflammageing.