A novel naturally occurring indole with anti-aging properties
from @ging by Shaday Michan
http://aging-academi...ndole-with.html
Indole-3-propionic acid (IPA), related to melatonin but which largely surpasses its antioxidant effects, was discovered in 1999 in the plasma and cerebrospinal fluid of humans and has been attributed a potent neuroprotective effect against deposition of amyeloid beta-protein, hallmark of Alzheimer’s disease. In order to improve the bioavailability of this compound, the group led by Pappolla, recently reported a new amphiphilic indol substance, IPAM, able to cross biological membranes and which in contrast to melatonin has long half-life and no pro-oxidant activity. Surprisingly, it was found that this molecule is also present in rat brain and confers the following anti-aging effects in mammalian mitochondrial:
1) Reverts age-dependent decline of rat mitochondrial proton motive force and energetic capacity.
2) Antagonizes toxin-induced mitochondrial damage in young and old mice brains triggered by the electron transport inhibitors such as doxorubicin and antimycin A, and the proton potential dissipater carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP).
3) Increases the activity of mitochondrial Complex I —generator of half the amount of free radicals produced by the mitochondria— and Complex IV, activities that tend to diminish through the course of aging.
4) Poses a potent antioxidant effect with no pro-oxidant intermediaries detected in vitro.
Furthermore, Poeggeler et al. used microscopic rotifers as an aging model system to explore the effect of IPAM on longevity and found that animals treated with this compound have increased size, fertility and 300% longer lifespan than their untreated peers. Additional insights into the biochemical mechanisms underling the effects of this indole will determine whether oxidative stress reduction is indeed the main cause of these anti-aging effects, or if rather deregulation of other molecular pathways leads to this phenotype.
