Basic Biology of Aging at the University of Washington

George M. Martin, Ph.D.


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Dr. Martin's full body of research concentrates on the process of biology, pathology, and chemistry of aging. His program mainstay, Gene Action in the Pathobiology of Aging, is in its 21st year. His group evaluates transgenic mice overexpressing genes that have the potential to protect the DNA of aging mammalian cells from oxidative damage, to enhance life span, and to retard age-related disorders (based at Duke University). As part of the National Long-term Care Survey, the laboratory isolates DNA from 1,500 persons plus DNA and mononuclear cells from an additional 2,000 persons. They then genotype APOE and three WRN polymorphisms, bank blood cells, pilot haplotype determinations from a subset of these individuals, and link the data back to Duke University where correlation of genotype to health and cognition status is made.

Other projects related to Alzheimer's disease include Genetic Instability and Knockout Mice, in which his laboratory creates and evaluates transgenic mouse models of Werner Syndrome; the kinetics of replication of T. Brucei in the blood stream of experimentally infected transgenic mice engineered to express either the human APOE 2, 3, or 4 alleles at the sites of their endogenous APOE loci; and a study of the modulation of expression of FE65, a facilitator of beta amyloidogenesis, in which they correlate expression of FE65 with levels of AD pathology and cognitive function.

Dr. Martin has been Attending Pathologist since 1959, Professor of Pathology since 1968, and Adjunct Professor of Genetics since 1975. He directed the Alzheimer Disease Research Center 1985-1999, and he founded and directed the Medical Scientist Training Program at the University of Washington 1970-1973. In 1992 he was elected Member, Institute of Medicine, National Academy of Sciences, and since 1993 he has been a Member, Scientific Advisory Board, Intramural Research Program, National Institute on Aging.

Selected Relevant Publications

  • Wang L, Hunt KE, Martin GM, Oshima J. Structure and function of the human Werner syndrome gene promoter: evidence for transcriptional modulation. Nucleic Acids Res 26:3480-3485, 1998.
  • Ogburn CE, Austad SN, Holmes DJ, Kiklevich JV, Gollahon K, Rabinovitch PS, Martin GM. Cultured renal epithelial cells from birds and mice: enhanced resistance of avian cells to oxidative stress and DNA damage. J Gerontology 53A:B287-B292, 1998.
  • Martin GM. Genetic approaches to aging research: opportunities for progress utilizing avian, murine and human species. In: Molecular Biology of Aging, Alfred Benzon Symposium 44. V Bohr, B Clark, T Stevnsner, eds. pp 17-24. Copenhagen, 1999.
  • Martin GM. Genes that modulate longevity and senescence. In: Paradoxes of Longevity. Foundation Ipsen, World Health Organization, 1999.
  • Martin GM, Oshima J, Gray MD, Poot MP. What geriatricians should know about the Werner syndrome. J Am Geriatr Soc 4:1136-1144, 1999.
  • Castro E, Ogburn C, Hunt K, Rilvis R, Louhija J, Penttinen R, Erkkola R, Panduro A, Riestra R, Piussan C, Deeb S, Wang L, Edland S, Martin GM, Oshima J. Polymorphisms at the Werner locus:I. newly identified polymorphisms, ethnic variability of 1367Cy/Arg, and its stability in a population of Finnish centenarians. Am J Med Genet 82:399-403, 1999.
  • Martin GM. APOE alleles and lipophylic pathogens. Neurobiol Aging 20:441-443, 2000.
  • Martin GM. Molecular mechanisms of late-life dementias. Exp Gerontol 35:439-443, 2000.
  • Castro E, Edland SD, Lee L, Ogburn CE, Deeb SS, Brown G, Panduro A, Riestra R, Tilvis R, Louhija J, Penttinen R, Erkkola R, Wang L, Martin GM, Oshima J. Polymorphisms at the Werner locus: II. 1074Leu/Phe, 1367Cys/Arg, longevity, and atherosclerosis. Am J Med Genet 95:374-380, 2000.
  • Ogburn CE, Carlberg K, Ottinger MA, Holmes DJ, Martin GM, Austad SN. Exceptional cellular resistance to oxidative damage in long-lived birds requires active gene expression. J Gerontol A Biol Sci Med Sci 56:B468-474, 2001.