A novel endogenous indole protects rodent mitochondria and extends rotifer lifespan
| Autor: | Kumar Sambamurti, Miguel A. Pappolla, Mark A. Smith, Sandra L. Siedlak, Burkhard Poeggeler, George Perry |
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| Rok vydání: | 2009 |
| Předmět: |
Aging
Indoles Longevity Geriatrics/Dementia Respiratory chain lcsh:Medicine Endogeny Rodentia Oxidative phosphorylation Mitochondrion Biology Protective Agents Oxidative Phosphorylation Melatonin Electron Transport 03 medical and health sciences 0302 clinical medicine medicine Animals lcsh:Science Inner mitochondrial membrane 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Multidisciplinary lcsh:R Metabolism Chemical Biology/Chemical Biology of the Cell Mitochondria chemistry Biochemistry lcsh:Q Biochemistry/Drug Discovery Energy Metabolism Reactive Oxygen Species 030217 neurology & neurosurgery medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 4, p e10206 (2010) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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