George M. Martin Symposium: Frontiers of Aging Research, September 17-18, 2002
In honor of Dr. George M. Martin’s 75th birthday and his innumerable contributions to aging research, the George M. Martin Symposium: Frontiers of Aging Research was held September 17-18, 2002 at the University of Washington, Seattle, Washington.
Dr. Martin’s research has for many years been concerned with the development of genetic approaches to the study of aging and age-related diseases in mammals. One
theme has been the plasticity of the genome of somatic cells. During this period a parallel series of biochemical, cytogenetic and somatic cell genetic studies on cells from aging mammals addressed various somatic mutational theories of aging; these have demonstrated
the importance of relatively large scale chromosomal types of mutation (summarized, in part, in Molecular Biology of Aging: Gene Stability and Gene _Expression, 1985). A more recent offshoot of this work has provided the first data on mutation frequencies in human epithelial cells in aging human subjects (Human Mol Genet 5:215, 1996).
These studies were reinforced by a long series of investigations of a remarkable human progeroid syndrome, the Werner syndrome, a recessive mutation that Dr. Martin and his colleagues mapped to chromosome 8, leading to the positional cloning of the Werner syndrome gene and its identification as a member of the RecQ helicase family (Science 272:258, 1996). Dr. Martin and colleagues have provided molecular evidence for the importance of intragenic deletions in the somatic cells of Werner syndrome subjects (Proc Natl Acad Sci USA 86:5893, 1989.) Cells from these patients were also shown to undergo accelerated “aging in vitro” (Lab Invest 23:86, 1970). At a more clinical level, Dr. Martin has systematized our knowledge of human genetic disorders from the point of view of their rich potential to elucidate specific aspects of the senescent phenotype (Birth Defects 14:5, 1978) and used this analysis to make inferences concerning the polygenic basis of aging.
In recent years, Dr. Martin has turned his attention to mechanisms of the aging of postreplicative cells, again using genetic approaches. He assembled a team of investigators to carry out a linkage analysis of familial Alzheimer disease, an effort that led to the assignment of the commonest form to chromosome 14 (Science 258:668, 1992) and to the mapping and positional cloning of a related locus on chromosome 1 (Science 269:917, 1995). New candidate genes were sought using the yeast protein interaction trap methodology. The latest contribution has been the synthesis of the first “knock-in” and “conditional knock-out” transgenic mouse models of human presenilin 1 dysfunction (Nature Med 5:101, 1999; Neuron 32: 2001).
The symposium in honor of Dr. Martin is sponsored by the Nathan Shock Center of Excellence in the Basic Biology of Aging; Office of the Dean, School of Medicine, University of Washington; the Ellison Medical Foundation; and Nippon Boehringer Ingelheim Company.
Charles J. Epstein
University of California - San Francisco
University of California - Irvine
University of California - San Diego
University of Wurzburg
University of Texas Health Science Center at San Antonio
Kelsey C. Martin
University of California - Los Angeles
University College, London
Mickey Fry, Technion
Israel Institute of Technology
University of Texas Health Sciences Center at San Antonio
University of Michigan
University of Idaho
University of Colorado
University of Newcastle
Texas Southwestern Medical Center
Gene Care, Kamakura, Japan