On Wed, Feb 4, 2015 at 2:48 AM, wrote:
If dNP did not have so many unfortunate adverse
effects in humans, even in very low doses, it would be an ideal drug not only
for weight loss and the metabolic syndrome, but also possibly as a primary
lifespan extending drug.
### While DNP is indeed quite dangerous in high doses (>500 mg/day), AFAIK it is benign in lower doses, or at least I am now aware of any studies showing dangerous side effects at low doses. I can tell you it greatly increases cold tolerance and lets you eat whatever you want without weight gain but at the cost of diminished physical performance.
The somewhat counterintuitive effects of uncouplers, mitophagy inducers, and anti-oxidants underscore the importance of various secondary responses to manipulation of mitochondria in determining the overall effects of drugs. Metformin stimulates mitophagy – one might imagine it should be bad for you (destroying mitochondria) yet in humans it prolongs survival. Anti-oxidants reduce ROS damage, one might expect them to be beneficial, yet their effects on human longevity are by no means clear. Uncouplers have not been sufficiently studied to allow conclusions about longevity in humans but I would not be surprised if they slowed aging if given at the right dose.
I would hypothesize that the best method for predicting the long-term impact of a drug on longevity would be to measure its effects on microheteroplasmy levels in treated animals or in humans, independently of short term changes in OXPHOS and ROS damage which are the usual focus in this field of research. Anything that limits microheteroplasmy is likely to be an anti-aging treatment. Luckily, with the advent of deep sequencing it possible to measure microheteroplasmy orders of magnitude cheaper than 10 years ago.