In an effort to better understand the biology of aging with an emphasis on mid-life changes that influence healthspan, we have undertaken a DNA microarray analysis of global gene expression profiles over time using Affymetrix gene chip arrays. Our experiment includes time points including the reproductive and post-reproductive periods, with a series of consecutive mid-life time points being covered. Studies in our lab and others have suggested that critical events during the mid-life of the nematode can influence the aging of this organism. For our analyses, we used supervised and unsupervised methods, including a clustering method developed in the Domany lab. Interestingly, we find a sharp change in the transcriptional levels of numerous genes at about 10 days post egg-lay. This abrupt change in gene expression on day 10 is consistent with a window of time identified previously by our lab as a time when mutations in the
age-1 gene are able to delay the deterioration of muscle tissue (Herndon et al., 2002, Nature, 419: 808-14). The abrupt change also correlates with a transition point at which autofluorescent biomarkers accumulate (see abstract by Gerstbrein et al., this volume). Since two similar microarray experiments already have been performed (Lund et al., 2001, Curr Biol. 12(18): 1566-73; Murphy et al., 2003, Nature, 424(6946):277-83), we attempted a detailed cross-comparison between data from all three experiments, using non-parametric techniques. Again, a dramatic change in gene expression was observed for some genes at time points corresponding to our day 10 time point. Approximately 100 genes show significant changes in gene expression over adulthood in all three studies. These expression changes might be relevant to rapid end-stage deterioration in old nematodes.