AGING AND ANTI-OXIDANT EXPRESSION IN MICE SELECTIVELY BRED FOR INCREASED VOLUNTARY EXERCISE





*A.M. Bronikowski, T. Morgan, T. Garland, Jr., P.A. Carter

Department of Zoology, U. Wisconsin, Madison WI
& School of Biological Sciences, Washington State U., Pullman WA




We studied how 16 generations of selection for increased voluntary wheel-running and access to running wheels affects aging and liver anti-oxidant expression in four replicate selectively-bred lines (“Selected”) and four replicate randomly-bred lines (“Control”). Age-specific mortality rates were estimated over the lifespan of mice in these lines divided among four treatment groups: “Selected Active” individuals were from selection lines and were housed with access to running wheels from weaning through death, “Selected Sedentary” individuals were from selection lines and were not housed with running wheels. The groups “Control Active” and “Control Sedentary” were mice from control lines housed as above. (Total N = 320, n per treatment group = 80). For both males and females, the post-maturation age-specific mortalities were highest in Control Active and Control Sedentary groups. Mortality was lower in Selected Active individuals and lowest in Selected Sedentary individuals (Gompertz parameters were significantly different in each treatment group based on maximum-likelihood estimation of parameter confidence intervals.) In all treatment groups, the pattern of mortality was low until 20 months of age, and steadily increased thereafter through 33 months of age.
Running can cause an increase in reactive oxygen metabolites (ROMs) in the mitochondria, and the accumulation of oxidative damage has been implicated in aging. Therefore, we measured the mRNA expression of mitochondrial superoxide dismutase (SOD2) and catalase (CAS) with the RNase-protection assay in sacrificed 20-month olds from these four groups (n = 40 mice per treatment group). The main effects of interest were activity and selection history, and were tested in a mixed model analysis-of-covariance. Also, because mice housed with running wheels exhibit a large amount of variation in running behavior, we performed a second statistical analysis substituting revolutions run in the week prior to death for activity group in the analysis. We found that running per se, rather than wheel-access affected CAS expression for both males and females; increased running revolutions corresponded to increased CAS expression. In females, this was especially true in mice from selectively bred lines. Additionally, three of four control lines had higher CAS expression than did the four selection lines. Neither selection history nor activity affected SOD2 expression; rather, lines varied such that the same three of four control lines had higher SOD2 expression than did the four selection lines.
We conclude from these studies that (i) genetic selection for increased voluntary exercise correlates with slower aging in these lines, (ii) exercise affects aging in these selection lines, but not in control lines, (iii) increased CAS and SOD2 expression at middle-age in three of four control lines correlates with faster aging in control mice. If indeed aging is caused in part the accumulation of oxidative damage, we may have predicted faster aging in mice from selection lines due to decreased anti-oxidant expression. The combined results of slower aging and lower anti-oxidant expression suggest that mice from selection lines may not produce as many ROMs as mice from control lines, despite the fact that they run significantly more.






Key words: mouse, exercise, superoxide-dismutase, catalase, age-specific mortality







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