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Hormesis in Aging and Neurodegeneration—A Prodigy Awaiting Dissection
Department of Life Science Engineering, HTW Berlin, University of Applied Sciences, Wilhelminenhofstraße 75A, Berlin 12459, Germany
Institute of Medical Genetics and Human Genetics, Charité—Universitätsmedizin Berlin, Augustenbruger Platz 1, Berlin 13353, Germany
* Author to whom correspondence should be addressed.
Received: 11 March 2013; in revised form: 16 May 2013 / Accepted: 17 May 2013 / Published: 25 June 2013
Abstract: Hormesis describes the drug action of low dose stimulation and high dose inhibition. The hormesis phenomenon has been observed in a wide range of biological systems. Although known in its descriptive context, the underlying mode-of-action of hormesis is largely unexplored. Recently, the hormesis concept has been receiving increasing attention in the field of aging research. It has been proposed that within a certain concentration window, reactive oxygen species (ROS) or reactive nitrogen species (RNS) could act as major mediators of anti-aging and neuroprotective processes. Such hormetic phenomena could have potential therapeutic applications, if properly employed. Here, we review the current theories of hormetic phenomena in regard to aging and neurodegeneration, with the focus on its underlying mechanism. Facilitated by a simple mathematical model, we show for the first time that ROS-mediated hormesis can be explained by the addition of different biomolecular reactions including oxidative damage, MAPK signaling and autophagy stimulation. Due to their divergent scales, the optimal hormetic window is sensitive to each kinetic parameter, which may vary between individuals. Therefore, therapeutic utilization of hormesis requires quantitative characterizations in order to access the optimal hormetic window for each individual. This calls for a personalized medicine approach for a longer human healthspan.
Keywords: hormesis; aging; neurodegenerative diseases (ND); reactive oxygen species (ROS); reactive nitrogen species (RNS); mathematical modeling; personalized medicine
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MDPI and ACS Style
Mao, L.; Franke, J. Hormesis in Aging and Neurodegeneration—A Prodigy Awaiting Dissection. Int. J. Mol. Sci. 2013, 14, 13109-13128.
Mao L, Franke J. Hormesis in Aging and Neurodegeneration—A Prodigy Awaiting Dissection. International Journal of Molecular Sciences. 2013; 14(7):13109-13128.
Mao, Lei; Franke, Jacqueline. 2013. "Hormesis in Aging and Neurodegeneration—A Prodigy Awaiting Dissection." Int. J. Mol. Sci. 14, no. 7: 13109-13128.