Genome instability is a hallmark of the aging process and has been implicated as a causal factor in aging since the 1950s. Thus far, it has been difficult to test if genome instability, i.e., genetic alterations that can vary from small base substitution mutations to large chromosomal changes, impacts cell function and contributes to the well-documented increase in disease risk at older age. The challenge in this respect is to quantitatively analyze mutations occurring randomly across cell populations, which cannot be done by sequencing DNA or RNA from bulk cell populations. We are developing single-cell approaches to quantitively assess multiple genetic end points, i.e., base substitutions, small INDELS, genome structural variation, copy number variation, chromosomal aneuploidy and retrotranspositions, in single cells isolated from humans at different time points during normal aging. Data will be presented on the frequency and spectrum of such mutations in human primary fibroblasts, lymphocytes, liver hepatocytes and mammary epithelial cells as a function of age.
Jan Vijg, Ph.D., is Professor and Chairman of the Department of Genetics at the Albert Einstein College of Medicine in New York since July, 2008. He received his Ph.D. at the University of Leiden, The Netherlands, in 1987. From 1990 to 1993 he was founder and Scientific Director of Ingeny B.V., a Dutch Biotechnology company. In 1993 he moved to Boston, to take up a position as Associate Professor of Medicine at Harvard Medical School. In 1998 he accepted an offer from the University of Texas Health Science Center in San Antonio, Texas, to become a Professor in the Department of Physiology. From 2006 to 2008 he was a Professor at the Buck Institute for Age Research in Novato, California. With his research team he was the first to develop transgenic mouse models for studying mutagenesis in vivo (in 1989) and has used these models ever since in studying the relationship between damage to the genome and aging. He has published over 300 scientific articles and three books, and is inventor or co-inventor on 8 patents.
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