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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on May 4, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/glp052
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Long-Lived Ames Dwarf Mice Are Resistant to Chemical Stressors

Alex F. Bokov1,2, Merry L. Lindsey1,3, Christina Khodr4, Marian R. Sabia1,5 and Arlan Richardson1,2,5,6

1 Sam and Ann Barshop Institute for Longevity and Aging Studies
2 Department of Physiology
3 Department of Medicine (Cardiology Division), University of Texas Health Science Center at San Antonio
4 Neurobiology Laboratories, Children's Memorial Research Center, Chicago, Illinois
5 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio
6 Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio

Address correspondence to Arlan Richardson, PhD, Professor and Director, Sam and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, Texas Research Park Campus, 15355 Lambda Drive—MSC 7755, San Antonio, TX 78245-3207. Email: richardsona{at}uthscsa.edu


  Abstract

To probe the connection between longevity and stress resistance, we compared the sensitivity of Ames long-lived dwarf mice and control littermates with paraquat, diquat, and dobutamine. In young adult animals, 95% of male and 39% of female controls died after paraquat administration, but no dwarf animals died. When the experiment was repeated at an older age or a higher dosage of paraquat, dwarf mice still showed greater resistance. Dwarf mice also were more resistant to diquat; 80% of male and 60% of female controls died compared with 40% and 20% of dwarf mice, despite greater sensitivity of dwarf liver to diquat. Dwarf mice were also less sensitive to dobutamine-induced cardiac stress and had lower levels of liver and lung F2-isoprostanes. This is the first direct in vivo evidence that long-lived Ames dwarf mice have enhanced resistance to chemical insult, particularly oxidative stressors.

Keywords Reactive oxygen species; Liver; Ames dwarf mice; Paraquat; Diquat

Received: November 5, 2008; Accepted: March 13, 2009

Decision Editor: Huber R. Warner, PhD


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