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.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23185716