A novel endogenous indole protects rodent mitochondria and extends rotifer lifespan

Aging is a multi-factorial process, however, it is generally accepted that reactive oxygen species (ROS) are significant contributors. Mitochondria are important players in the aging process because they produce most of the cellular ROS. Despite the strength of the free-radical hypothesis, the use o...

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Bibliographic Details
Published in:PloS one 2010-04, Vol.5 (4), p.e10206-e10206
Main Authors: Poeggeler, Burkhard, Sambamurti, Kumar, Siedlak, Sandra L, Perry, George, Smith, Mark A, Pappolla, Miguel A
Format: Article
Language:English
Subjects:
Acids
Aging
Animal models
Animals
Antioxidants
Antioxidants (Nutrients)
Binding sites
Bioavailability
Biochemistry/Drug Discovery
Cell growth
Chemical Biology/Chemical Biology of the Cell
Dopamine
Electron Transport
Electron transport chain
Energy Metabolism
Enzymes
Ethanol
Fibroblasts
Geriatrics/Dementia
Homeostasis
Indole
Indoles
Indoles - pharmacology
Life span
Longevity - drug effects
Melatonin
Metabolism
Metabolites
Mitochondria
Mitochondria - drug effects
Neurosciences
Neurotoxicity
Oxidative Phosphorylation
Oxidative stress
Oxidizing agents
Oxygen
Pathology
Phosphorylation
Physiological aspects
Protective Agents
Reactive Oxygen Species
Rodentia
Rodents
Schizophrenia
Senescence
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Summary:Aging is a multi-factorial process, however, it is generally accepted that reactive oxygen species (ROS) are significant contributors. Mitochondria are important players in the aging process because they produce most of the cellular ROS. Despite the strength of the free-radical hypothesis, the use of free radical scavengers to delay aging has generated mixed results in vertebrate models, and clinical evidence of efficacy is lacking. This is in part due to the production of pro-oxidant metabolites by many antioxidants while scavenging ROS, which counteract their potentially beneficial effects. As such, a more effective approach is to enhance mitochondrial metabolism by reducing electron leakage with attendant reduction of ROS generation. Here, we report on the actions of a novel endogenous indole derivative, indolepropionamide (IPAM), which is similar in structure to melatonin. Our results suggest that IPAM binds to the rate-limiting component of oxidative phosphorylation in complex I of the respiratory chain and acts as a stabilizer of energy metabolism, thereby reducing ROS production. IPAM reversed the age-dependent decline of mitochondrial energetic capacity and increased rotifer lifespan, and it may, in fact, constitute a novel endogenous anti-aging substance of physiological importance.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0010206