title: Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs.
abstract: Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase-depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span.
authors.affiliation: Department of Animal Biology-II (Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López-Torres
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Campo
authors.forename: A
authors.initials: A
authors.lastname: Fernandez
authors.forename: C
authors.initials: C
authors.lastname: Barba
authors.forename: G
authors.initials: G
authors.lastname: Barja de Quiroga
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002374:Catalase / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D005980:Glutathione Reductase / Q000096:biosynthesis*; D015227:Lipid Peroxidation / Q000187:drug effects; D008062:Lipofuscin / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects*; D008854:Microscopy, Electron; D010101:Oxygen Consumption / Q000187:drug effects; D011898:Ranidae; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005609:Free Radicals; D008062:Lipofuscin; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase