title: The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.
abstract: Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept "Redox-stress Response Capacity (RRC)", which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Meng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lv
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Qiao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Li
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049, China.
authors.forename: Yazi
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049, China; Beijing Institute for Brain Disorders, 10 Xitoutiao, Youanmen, Beijing 100069, China. Electronic address: changchen@moon.ibp.ac.cn.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects; D002675:Child, Preschool; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D061251:Primary Cell Culture; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D051267:NF-E2-Related Factor 2; D002374:Catalase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D051549:Glutathione S-Transferase pi; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D010269:Paraquat
keywords: Aging; Oxidative stress; RRC; Redox; Redox-stress Response Capacity