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Geroscientists are united in the belief that basic research on the fundamental mechanisms of biological aging are the major risk factors of virtually all of the major geriatric disorders and that such knowledge has great potential to lead to major delays, ameliorations and, perhaps, preventions of many such disorders.
— George M. Martin, M.D.

George M. Martin, M.D.

Professor of Pathology Emeritus, University of Washington

Dr. Martin received his BS and MD degrees from the University of Washington and has been a member of its faculty since 1957. After an internship at the Montreal General Hospital and a residency in anatomic pathology at the University of Chicago, he pursued postdoctoral research in somatic cell genetics under Professor Guido Pontecorvo at Glasgow University, where he worked with Aspergillus nidulans and human cell cultures. Other postdoctoral experiences have included research in molecular biology with Francois Gros in Paris and in experimental embryology with Henry Harris and Richard Gardner at Oxford University. He has also done medical genetics fieldwork in India. Honors for his research have included the Brookdale, Kleemeier and Paul Glenn Foundation awards of the Gerontological Society of America, the Irving Wright Award of the American Federation for Aging Research, the American Aging Association Research Medal and Distinguished Scientist Award, the Pruzanski Award of the American College of Medical Genetics, a World Alzheimer Congress Lifetime Achievement Award and election to the National Academy of Medicine.  He has also had the honor of having served as Past Presidents of the Tissue Culture Association, the Gerontological Association of America and the American Federation for Aging Research. Dr. Martin’s research has focused upon genetic approaches to the study of aging and age-related diseases, with a focus upon what he has characterized as segmental progeroid syndromes, virtually all of which were shown to support a major role for genomic instability as a fundamental mechanism of aging. A more recent research interest also seeks evidence for age-related patterns of variegated gene expression as an antagonistic pleiotropic mechanism of aging.

FOCUS AREAS

Alzheimer’s Disease Research. Dr. Martin 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 and to the mapping and positional cloning of a related locus on chromosome 1. New candidate genes were sought using the yeast protein interaction trap methodology. This work has led to a series of papers on an adaptor protein (FE65) that is of importance in the modulation of the function of the beta amyloid precursor protein; polymorphisms at that locus were shown to play a role in the susceptibility to Alzheimer disease in very old individuals.

Genetic Approaches to Aging 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. His lab has contributed to our understanding of a number of mechanisms for the heritable alteration of genetic information 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. An offshoot of this work provided the first data on mutation frequencies in human epithelial cells in aging human subjects. 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’s group and Japanese investigators mapped to chromosome 8. This led to the positional cloning of the Werner syndrome gene and its identification as a member of the RecQ helicase family. Dr. Martin and colleagues have provided molecular evidence for the importance of intragenic deletions in the somatic cells of Werner syndrome subjects. Cells from these patients were also shown to undergo accelerated "aging in vitro" . This latter line of research provided the first evidence for the limited replicative potential of cells of the vascular wall. Together with Drs. Tom Norwood and William Pendergrass, the Martin lab also carried out the first cell fusion experiments for the investigation of dominance/recessivity relationships between old cells, young cells and "immortal" cells and demonstrated that the decline of growth potential involved gradual and variable attenuations of clonal growth.

aging critical publications

  • DOI:Grella SL, Neil JM, Edison HT, Strong VD, Odintsova IV, Walling SG, et al. Locus coeruleus phasic, but not tonic, activation initiates global remapping in a familiar environment. J Neurosci 2018 Nov 26; :. doi:10.1523/JNEUROSCI.1956-18.2018. Pubmed PMID: 30478033

  • Sargolzaeiaval F, Zhang J, Schleit J, Lessel D, Kubisch C, Precioso DR, et al. CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures. Mol Genet Genomic Med 2018 Nov 4; :. doi:10.1002/mgg3.495. Pubmed PMID: 30393977

  • Misra MK, Augusto DG, Martin GM, Nemat-Gorgani N, Sauter J, Hofmann JA, et al. Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop. Hum Immunol 2018 Oct 12; :.doi:10.1016/j.humimm.2018.10.003. Pubmed PMID: 30321631

  • Del Rosso J, Swanson N, Berman B, Martin GM, Lin T, Rosen T. Imiquimod 2.5% and 3.75% Cream for the Treatment of Photodamage: A Meta-analysis of Efficacy and Tolerability in 969 Randomized Patients. J Clin Aesthet Dermatol 2018 Sep 1; 11(9):28-31. Pubmed PMID: 30319728

  • Horvath S, Oshima J, Martin GM, Lu AT, Quach A, Cohen H, et al. Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and <i>ex vivo</i> studies. Aging (Albany NY) 2018 Jul 26; 10(7):1758-1775.doi:10.18632/aging.101508. Pubmed PMID: 30048243