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. 2000 Dec 5;97(25):13726-31.
doi: 10.1073/pnas.260496697.

Genome-wide study of aging and oxidative stress response in Drosophila melanogaster

S Zou  1 , S Meadows, L Sharp, L Y Jan, Y N Jan
Affiliations

Genome-wide study of aging and oxidative stress response in Drosophila melanogaster

S Zou et al. Proc Natl Acad Sci U S A. .

Abstract

Aging is a universal but poorly understood biological process. Free radicals accumulate with age and have been proposed to be a major cause of aging. We measured genome-wide changes in transcript levels as a function of age in Drosophila melanogaster and compared these changes with those caused by paraquat, a free-radical generator. A number of genes exhibited changes in transcript levels with both age and paraquat treatment. We also found genes whose transcript levels changed with age but not with paraquat treatment. This study suggests that free radicals play an important role in regulating transcript levels in aging but that they are not the only factors. This genome-wide survey also identifies candidates for molecular markers of aging.

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Figures

Figure 1
Figure 1
Survival curve of w1118. Two independent experiments, indicated by open or closed squares, were performed by using 172 and 156 males, respectively. The curve was generated by fitting data from both experiments. The median lifespan in these experiments was approximately 35 days.
Figure 2
Figure 2
CLUSTER image of 132 age-regulated ESTs. Each column represents one of seven time points: 3, 10, 15, 25, 30, 40, and 50 days. Except for 3 days (the control), each time point has two sets of data, which are shown side by side in columns. Each row represents the expression pattern of a single EST. Red indicates up-regulation in the experimental sample, and green represents down-regulation. Gray indicates missing data. Identities of some age-regulated ESTs are provided on the right side of the CLUSTER image, placed in the same order as their relative position in the cluster image. Each EST is labeled with its clone identification code followed by the gene name or the name of its homolog. ESTs with sequence error in this study are indicated by the symbol !. ESTs encoding an uncharacterized protein with homology to a known protein are marked by ˜. The ESTs marked by three asterisks (***) represent those coregulated with age and oxidative stress.
Figure 3
Figure 3
Transcript profiles of four classes of genes whose transcript levels changed with age or oxidative stress. These genes were selected from the 329 ESTs whose transcript levels are significantly altered with aging, oxidative stress, or both. Each column represents 1 of 11 time points: 3, 10, 15, 25, 30, 40, and 50 days for the aging experiments and 3, 12, 25, and 34 h for paraquat experiments. Except for 3 days (the control), each time point has two sets of data, which are shown side by side in columns. The ESTs with clone identification codes and gene names are listed in the same order as their relative positions in the CLUSTER image. The symbols and color coding used in this figure are the same as those used in Fig. 2. The ESTs with the same names marked by a single asterisk (*) have the same sequences.
Figure 4
Figure 4
CLUSTER image. (A) CLUSTER image of 295 age-regulated and/or paraquat-regulated ESTs. The cluster is subdivided further into 20 clusters, indicated by the number. The symbols and color coding used in this figure are the same as those used in Fig. 3. Correl. represents Pearson's correlation coefficient. (B) Gene list. The ESTs with clone identification codes and sequence information are shown with Cy5/Cy3 ratios at six time points: 30, 40, and 50 days for the aging experiments and 12, 25, and 34 h for the paraquat experiments. Two independent values for each time point are listed side by side. The order of the ESTs in the table is the same as their relative positions in the cluster image shown in A. Cluster identification is indicated by “c” followed by the number, and coded with two colors—green indicates down-regulation, and red indicates up-regulation.
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