Abstract
Oxidative damage has been proposed as an important factor in the progression of pathological and non-pathological age-related functional declines. Here, we examine functional deterioration in short-lived flies mutant for the mitochondrial antioxidant Manganese Superoxide Dismutase (Sod2). We find that the decline of several functional measures of aging occurs, in an accelerated fashion, in Sod2 mutants. Olfactory behavior, locomotor ability and cardiac performance were all seen to decline rapidly in Sod2 mutants. On average, functional declines in Sod2 mutants occur in a pattern similar to that seen in late-life Drosophila with a normal complement of Sod2. In longitudinal experiments, however, we find that functional failures occur in every possible sequence in Sod2 mutants. Significantly, failure of these functional measures is not irreversible, as spontaneous functional recovery was sometimes observed. These findings support a model where ROS-related damage strikes at multiple organ systems in parallel, rather than a “chain of dominos” model, in which primary organ failure contributes to the deterioration of further organ systems.
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Acknowledgments
This work was supported by grants from the American Heart Association and the Glenn Foundation For Biological Mechanisms of Aging to R.J.W. and by the American Federation of Aging Research and the National Institutes of Health to M.G.
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10522_2008_9210_MOESM1_ESM.doc
Supplementary Table 1 Longitudinal measurements including spontaneous ambulation, response to stimuli, and heart beating for Sod2 −/−, Sod2 −/+, and Sod2 revertants at 3 h intervals. For each genotype, 12 males and 12 females were used. Scoring is done in a binary fashion with a ‘+’ or ‘−’ indicating presence or absence of function. (DOC 804 kb)
10522_2008_9210_MOESM2_ESM.doc
Supplementary Table 2 Heart rate (Hz) data for Sod2 −/−, Sod2 −/+, and Sod2 revertants at 3 h intervals. For each genotype, 12 males and 12 females were used. (DOC 153 kb)
10522_2008_9210_MOESM3_ESM.doc
Supplementary Table 3 Longitudinal measurements for y 1 w 1 including spontaneous ambulation, response to stimuli and heart beating on a daily interval. For this experiment, ten males and eight females were used. Scoring is done in a binary fashion with a ‘+’ or ‘−’ indicating presence or absence of function. Day one on the graph represents day one of observation, at which flies were 64 days of age. (DOC 512 kb)
10522_2008_9210_MOESM4_ESM.mpg
Supplementary Movie 1 This video illustrates the heartbeat of a representative Sod2 revertant fly at 24 h of age. The beat is consistent throughout the 10 s with no pauses or rapid fluxes in beating. (MPG 121 kb)
10522_2008_9210_MOESM5_ESM.mpg
Supplementary Movie 2 This video illustrates the heartbeat of a representative Sod2 −/− fly at 24 h of age. The beat is inconsistent, showing a long pause and then rapid beating directly after. (MPG 121 kb)
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Piazza, N., Hayes, M., Martin, I. et al. Multiple measures of functionality exhibit progressive decline in a parallel, stochastic fashion in Drosophila Sod2 null mutants. Biogerontology 10, 637–648 (2009). https://doi.org/10.1007/s10522-008-9210-2
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DOI: https://doi.org/10.1007/s10522-008-9210-2