title: Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria.
abstract: We describe the effects of mitochondrially targeted catalase (MCAT) expression on end-of-life pathology in mice using detailed semiquantitative histopathological evaluation. We previously reported that the median and maximum life spans of MCAT mice were extended relative to those of wild-type littermates. We now report that MCAT expression is associated with reduced malignant nonhematopoietic tumor burden, reduced cardiac lesions, and a trend toward reduced systemic inflammation, with no effect on hematopoietic neoplasia or glomerulonephropathy. Combined disease burden and comorbidity are also reduced, and MCAT expression is not associated with any detrimental clinical effects. The results suggest that oxidative damage is involved in aging of C57BL/6J mice via modulation of a subset of age-associated lesions. Antioxidant interventions targeting mitochondria may therefore be a viable strategy for prevention or postponement of some age-associated diseases. The variability of the MCAT effect across tissues, however, illustrates the importance of developing semiquantitative histopathology for assessment of comorbidity in life-span studies.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA 98195-7190, USA. treuting@u.washington.edu
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Linford
authors.forename: Sue E
authors.initials: SE
authors.lastname: Knoblaugh
authors.forename: M J
authors.initials: MJ
authors.lastname: Emond
authors.forename: John F
authors.initials: JF
authors.lastname: Morton
authors.forename: George M
authors.initials: GM
authors.lastname: Martin
authors.forename: Peter S
authors.initials: PS
authors.lastname: Rabinovitch
authors.forename: Warren C
authors.initials: WC
authors.lastname: Ladiges
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D002374:Catalase / Q000378:metabolism*; D015897:Comorbidity; D004195:Disease Models, Animal; D008136:Longevity; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase