Efficacy of methuselah gene mutation toward tolerance of dichlorvos exposure in Drosophila melanogaster

• Prolonged exposure of Drosophila melanogaster to DDVP reduces life span and health span.
• Flies with a mth mutation (mth1) resisted life-span reduction from DDVP exposure.
• mth1 flies exhibited improved organismal fitness against prolonged DDVP exposure.
• mth1 flies resisted DDVP-induced oxidative damage from prolonged exposure.
• DDVP-exposed mth1 flies retained cellular and organismal tolerance up to middle age.

Adverse reports on the exposure of organisms to dichlorvos (DDVP; an organophosphate insecticide) necessitate studies of organismal resistance/tolerance by way of pharmacological or genetic means. In the context of genetic modulation, a mutation in methuselah (mth; encodes a class II G-protein-coupled receptor (GPCR)) is reported to extend (~35%) the life span of Drosophila melanogaster and enhance their resistance to oxidative stress induced by paraquat exposure (short term, high level). A lack of studies on organismal tolerance of DDVP by genetic modulation prompted us to examine the protective efficacy of mth mutation in exposed Drosophila. Flies were exposed to 1.5 and 15.0 ng/ml DDVP for 12–48 h to examine oxidative stress endpoints and chemical resistance. After prolonged exposure of flies to DDVP, antioxidant enzyme activities, oxidative stress, glutathione content, and locomotor performance were assayed at various days (0, 10, 20, 30, 40, 50) of age. Flies with the mth mutation (mth1) showed improved chemical resistance and rescued redox impairment after acute DDVP exposure. Exposed mth1 flies exhibited improved life span along with enhanced antioxidant enzyme activities and rescued oxidative perturbations and locomotor insufficiency up to middle age (~20 days) over similarly exposed w1118 flies. However, at late (≥30 days) age, these benefits were undermined. Further, similarly exposed mth-knockdown flies showed effects similar to those observed in mth1 flies. This study provides evidence of tolerance in organisms carrying a mth mutation against prolonged DDVP exposure and further warrants examination of similar class II GPCR signaling facets toward better organismal health.