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N-acetyl-L-cysteine (NAC) is a derivative of the sulphur-containing amino acid L-cysteine with potential anti-aging properties. We studied 3 Drosophila species with contrast longevity differences ( D. virilis is longest-lived, D. kikkawai is shortest-lived and D. melanogaster has moderate lifespan) to test the effects of NAC at 8 different concentrations (from 10 nM to 100 mM) on the lifespan, stress-resistance and locomotor activity. Except the adverse effects of highest (10 mM and 100 mM) concentrations NAC demonstrated sexually opposite and male-biased effects on Drosophila lifespan, stress-resistance and locomotor activity and not satisfied the criteria of a geroprotector in terms of the reproducibility of lifespan extending effects in different model organisms. The concentration- and sex-dependent changes in the relative expression levels of the antioxidant genes ( Cat/CG6871 and Sod1/CG11793 ) and genes involved in hydrogen sulfide biosynthesis ( Cbs/CG1753 , Eip55E/CG5345 and Nfs1/CG12264 ) suggest the involvement of hormetic mechanisms in the geroprotective effects of NAC.

Effects of N-acetyl-L-cysteine on lifespan, locomotor activity and stress-resistance of 3 Drosophila species with different lifespans