Minocycline effect on life and health span of Drosophila melanogaster.
Клучни зборови
Апстракт
Up-regulation of kynurenine (KYN) pathway of tryptophan (TRP) was suggested as one of the mechanisms of aging and aging-associated disorders. Genetic and pharmacological impairment of TRP - KYN metabolism resulted in prolongation of life span in Drosophila models. Minocycline, an antibiotic with anti-inflammatory, antioxidant and neuroprotective properties independent of its antibacterial activity, inhibited KYN formation from TRP. Since minocycline is the only FDA approved for human use medication with inhibitory effect on TRP - KYN metabolism, we were interested to study minocycline effect on life- and health-spans in Drosophila model. Minocycline (0.87mM) prolonged mean, median and maximum life span of wild-type Oregon Drosophila melanogaster of both genders. Minocycline (0.87 mM) stimulated vertical climbing in male flies. Minocycline dose-dependently decreased quantity and survivorship of pupae of filial generation. Minocycline might be a promising candidate drug for anti-aging intervention and treatment of aging-associated medical and psychiatric disorders. The role of TRP - KYN metabolism in the mechanisms of minocycline-effect on life- and health-span might be elucidated by the future assessment of minocycline effects in Drosophila mutants naturally or artificially knockout for genes impacting the key enzymes of KYN pathway of TRP metabolism.