Kynurenine-Tryptophan Metabolism and Fly Longevity
Metabolism is a very complex set of overlapping mechanisms, feedback loops, and networks of protein interactions. So even if there are only a few core methods of extending life by altering metabolism in a species, we should expect to see scores of different ways to trigger some or all of that alteration - and with widely varying side-effects. This is one of the present challenges facing those researchers who focus on how metabolism and genes determine natural variations in longevity: mapping it all for any one species is a vast task.
Here is one example of ongoing research drawn from among the many ways to make flies live longer:
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 prolonged mean, median and maximum life span of wild-type Oregon Drosophila melanogaster of both genders [and] might be a promising candidate drug for anti-aging intervention. [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.