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

Abstract

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.

Medical and Dietary Uses of N-Acetylcysteine

“…Due to its capacity to break down biofilms and improve antibiotic permeability, it is promising as an adjuvant antimicrobial drug [75]. Several pre-clinical studies have also demonstrated that NAC supplementation leads to life extension and diminished effects of aging, in invertebrates [76,77,78,79] as well as mammals [80] and in human breast epithelial stem cells [81]. Such findings have yet to be replicated in humans.…”

Interactions between gut microbiota and skeletal muscle

“…As a potentially interesting supplement in relation with the GM, N-acetyl-L-cysteine, a precursor of the biologic antioxidant glutathione, was shown to inhibit muscle fatigue in humans 101 and to display male-specific effects on Drosophila lifespan, stress-resistance and locomotor activity. 102 Interestingly, the benefits of N-acetyl-L-cysteine against dysbiosis and glucose metabolic disorders were recently shown in high-fat diet-fed mice. 103 In addition, apelin was identified as a diagnostic tool of early sarcopenia and a potential target to prevent muscle weakness in a study using mouse models and participants of Multidomain Alzheimer Prevention Trial (MAPT study) and Life-P. 104 Production of the peptide is induced by muscle contraction in an age-dependent manner and increases muscle strength.…”

“…As a potentially interesting supplement in relation with the GM, N-acetyl-L-cysteine, a precursor of the biologic antioxidant glutathione, was shown to inhibit muscle fatigue in humans 101 and to display male-specific effects on Drosophila lifespan, stress-resistance and locomotor activity. 102 Interestingly, the benefits of N-acetyl-L-cysteine against dysbiosis and glucose metabolic disorders were recently shown in high-fat diet-fed mice. 103 …”

Effects of unpaired 1 gene overexpression on the lifespan of Drosophila melanogaster

“…As the JAK/STAT pathway is evolutionarily conserved it may be possible to discover compounds that fit the criteria of geroprotector [48]. In our prior work we explored the effects of a variety of interventions on the Drosophila lifespan [49–53]. The new pathway analysis algorithms enable us to identify the pharmacological interventions for modulation of the levels of expression of individual genes and networks.…”