title: An oxidative fluctuation hypothesis of aging generated by imaging H₂O₂ levels in live Caenorhabditis elegans with altered lifespans.
abstract: Reactive oxygen species (ROS) are important factors mediating aging according to the free radical theory of aging. Few studies have systematically measured ROS levels in relationship to aging, partly due to the lack of tools for detection of specific ROS in live animals. By using the H₂O₂-specific fluorescence probe Peroxy Orange 1, we assayed the H₂O₂ levels of live Caenorhabditis elegans with 41 aging-related genes being individually knocked down by RNAi. Knockdown of 14 genes extends the lifespan but increases H₂O₂ level or shortens the lifespan but decreases H₂O₂ level, contradicting the free radical theory of aging. Strikingly, a significant inverse correlation between lifespan and the normalized standard deviation of H₂O₂ levels was observed (p < 0.0001). Such inverse correlation was also observed in worms cultured under heat shock conditions. An oxidative fluctuation hypothesis of aging is thus proposed and suggests that the ability of animals to homeostatically maintain the ROS levels within a narrow range is more important for lifespan extension than just minimizing the ROS levels though the latter still being crucial.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Xinmiao
authors.initials: X
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Dickinson
authors.affiliation: Department of Chemistry and the Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. Electronic address: chrischang@berkeley.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: changzy@pku.edu.cn.
authors.forename: Zengyi
authors.initials: Z
authors.lastname: Chang
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008136:Longevity; D018384:Oxidative Stress; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
keywords: Aging; Caenorhabditis elegans; Hydrogen peroxide; Oxidative fluctuation hypothesis of aging; Oxidative stress