Ial free radical theory of aging (MFRTA) was provided by Denham
Ial free radical theory of aging (MFRTA) was provided by Denham Harman [1,2], who recognized the possibility of a connection between mitochondrial oxidative phosphorylation, oxygen free radical formation, cellular damage and the general degenerative phenotype of aging. This theory continued to grow and gain acceptance and by the beginning of the next decade was suggested to be perhaps the major underlying cause of aging [3]. Originally envisioned as a collection of free radical processes that had their sources and primary targets within mitochondria, the theory had by 1981 grown to encompass non-mitochondrial targets and phenomena, including amyloid plaques in the brain and cancer. By the 21st century, the basic ideas espoused in the MFRTA had grown to include a vast array of connections between mitochondrial free radical production* Correspondence: [email protected] 1 Department of Biological Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada Full list of author information is available at the end of the articleand age-related phenomena in most cell types, tissues and physiological processes (for example, [4-7]). Now into its fifth decade, the MFRTA has provided the basic framework for thousands of studies in the field of aging that have linked mitochondrial free radical production to cellular deficits associated with aging. As the number of publications that address the MFRTA at some level has grown, the theory has inevitably shown signs of fallibility, if not evidence of an outright midlife crisis. This situation arises in part as a result of the wealth of new information and our continually developing understanding of mitochondrial oxygen free radical metabolism, mitochondrial repair and turnover, and macromolecular repair processes elsewhere in the cells that were unavailable when the theory was first postulated. In this review, we present several key predictions arising from the MFRTA that have now been comprehensively tested and L-660711 sodium salt cost summarize these experimental results. We then briefly present a more refined view of mitochondrial ROS as participants in intracellular redox regulated processes?2014 Stuart et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Stuart et al. Longevity Healthspan 2014, 3:4 http://www.longevityandhealthspan.com/content/3/1/Page 2 ofand pathways, rather than as indiscriminately damaging toxins.ReviewPredictions based on the MFRTAthat demands considering the signaling-based effects of mitochondrial ROS on specific cellular processes. We conclude the review by highlighting the emerging roles of ROS as conveyors of information within animal cells.The role of oxygen in the MFRTAThe modern version of the MFRTA proposes that the progenitor reactive oxygen species (ROS) superoxide (O2?) originating from several mitochondrial enzymes, including respiratory complexes I, II and III [8] enters into a number of secondary reactions leading to other ROS that ultimately PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/25432023 react with and indiscriminately damage cellular macromolecular structures. The affected cells accumulate such.
Posted inUncategorized