Changes in Gene Expression with Age


Changes in gene expression with age have been documented in mitotic human fibroblasts (Ly DH, Lockhart DJ, Lerner RA, and Schultz PG, "Mitotic Misregulation and Human Aging," Science 2000; Vol. 287, pp. 2486-2492); human vastus lateralis muscle cells (Welle S, Bhatt K, and Thornton CA. "High-Abundance mRNAs in Human Muscle: Comparison Between Young and Old," J. Appl. Physiol. 2000; Vol. 89, pp. 297-304); and in terminally differentiated vastus lateralis muscle cells of rhesus monkeys (T. Kayo, D.B. Allison, R. Weindruch, and T. A. Prolla, "Influences of Aging and Caloric Restriction on the Transcriptional Profile of Skeletal Muscle from Rhesus Monkeys." Proc Natl. Acad. Sci. 2001; Vol. 98, pp. 5093-5098) by means of DNA microarray chips or SAGE. The putative kinetics are illustrated in the above graph in which the number of genes that change expression in human fibroblasts appears to occur in virtually a straight line, while changes in rhesus muscle cells form a "hockey stick" shaped curve. Data for human muscles cells does not seem to be significantly different from that of fibroblasts, but only 2 points are present. Data from only 3 individuals form the basis of each point for rhesus monkeys and human fibroblasts except for the middle aged human sample that came from 2 individuals. Data from 8 individuals were employed for each point of the human muscle cells. Such limited numbers for two of the curves require caution in their interpretation while demonstrating the need for additional data. Whether the distinctly different patterns are due to cell type, species differences, methodology, or simply sampling error await further investigation. One species difference is maximum life span which for rhesus monkeys is about one third that of humans. The SAGE methodology used by Welle et al differed from the other two studies. The number of genes shown to change expression with age in human fibroblasts is based on a manual count of those published plus those listed in supplemental information at . Accurate determination of the kinetics of gene expression with age is essential for utilization of genes as biomarkers of aging. Collaboration of all individuals and organizations that possess relevant data will greatly facilitate development of this methodology.