George M. Martin, M.D.
Department of Pathology
University of Washington
Recent Publications
(Selected from approximately 350 peer-reviewed publications.)
1. Schellenberg GD, Bird TD, Wijsman EM, Orr HT, Anderson L, Nemens E, White JA,
Bonnycastle L, Weber JL, Alonso ME, Potter H, Heston LL, Martin GM. Genetic linkage
evidence for a familial Alzheimer's disease locus on chromosome 14. Science 258:668-671,
1992.
2. Fukuchi K, Sopher B, Martin GM. Neurotoxicity of -Amyloid. Nature 361:122-123, 1993.
3. Fukuchi K, Ohman T, Dang N, Smith AC, Furlong CE, Martin GM. Overexpression of
cDNAs for -amyloid precursor proteins 695, 751, and 770 enhance the secretion of amyloid precursor protein derivatives and the survival of P19-derived neurons. J
Neurochem 66:2201-2204, 1996.
4. Bressler SL, Gray MD, Sopher BL, Hu Q, Hearn MG, Pham DG, Dinulos MB, Fukuchi K-I,
Sisodia SS, Miller MA, Disteche CM, Martin GM. cDNA cloning and chromosome mapping
of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human
beta-amyloid precursor protein and its homologues with the mouse Fe65 protein. Hum Mol
Genet 5(10): 1589-1598, 1996.
5. Fukuchi K, Ho L, Younkin SG, Kunkel DD, Ogburn CE, LeBoeuf RC, Furlong CE, Deeb SS,
Nochlin D, Sumi SM, Wegiel J, Wisniewski HW, Martin GM. High levels of circulating betaamyloid peptide do not cause cerebral -amyloidosis in transgenic mice. Am J Path 149:219227, 1996.
6. Guo Q, Sopher BL, Furukawa K, Pham DG, Robinson N, Martin GM and Mattson MP.
Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor
withdrawal and amyloid -peptide: involvement of calcium and oxyradicals. J Neurosci
17:4212-4222, 1997.
7. Kukull WA, Martin GM. APOE Polymorphisms and Late-Onset Alzheimer Disease: The
Importance of Ethnicity. JAMA 279:788-789, 1998
8. Hu Q, Kukull WA, Bressler SL, Gray MD, Cam JA, Larson E, Martin GM, Deeb SS. The
human FE65: genomic structure and an intronic bi-allelic polymorphism associated with
sporadic dementia of the Alzheimer type. Hum Genet 103:295-303, 1998.
9. Jin LW, Hearn MG, Ogburn CE, Dang N, Nochlin D, Ladiges WC, Martin GM. Transgenic
mice over-expressing the C-99 fragment of betaPP with an alpha-secretase site mutation
develop a myopathy similar to inclusion body myositis. Am J Pathol 153(6):1679-1686,
1998.
10. Guo Q, Fu W, Sopher B, Miller MW, Ware CB, Martin GM, Mattson MP. Increased
vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in
mice. Nat Med 5:101-106, 1999.
11. Guo, Q., Sebastian, L., Sopher, B.L., Miller, M.W., Ware, C.B., Martin, G.M., Mattson, M.P.
Increased vulnerability of hippocampal neurons from presenilin-1 mutuant knockin mice
to amyloid beta-peptide toxicity: central roles of superoxide production and caspase
activation. J Neurochem 72:1019-1029, 1999.
12. Hu, Q., Hearn, M.G., Jin, L-W., Bressler, S.B., Martin, G.M. Alternatively spliced isoforms of
FE65 serve as neuron-specific and non-neuronal markers. J Neurosci Res 58:632-640,
1999.
13. Hu QB, Jin LW, Starbuck MY, et al. Broadly altered expression of the mRNA isoforms of
FE65, a facilitator of beta amyloidogenesis, in Alzheimer cerebellum and other brain regions
J Neurosci Res 60:73-86, 2000
14. Schriner, S.E., Ogburn, C.E., Smith A.C., et al. Levels of DNA damage are unaltered in mice
overexpressing human catalase in nuclei. Free Radical Bio Med. 29: 664-673, 2000.
15. Feng, R., Rampon, C., Tang, Y., Shrom, D., Jin, J., Kyin, M., Sopher, B., Martin, G.M., Kim,
S., Langdon, R.B., Sisodia, S.S., and Tsien, J.Z., Deficient Neurogenesis in ForebrainSpecific Presenilin-1 Knockout Mice is Associated with Reduced Clearance of Hippocampal
Memory Traces. Neuron. 32: 911-926, 2001.
16. 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.
Journals of Gerontology Series A – Biological Sciences and Medical Sciences. 56:B468B474, 2001.
17. Martin, G.M. Gene Action in the Aging Brain: An Evolutionary Biological Perspective.
Neurobiol Aging 23:647-654, 2002.
18. Hu, Q., Cool, B.H., Wang, B., Hearn, M.G., and Martin, G.M. A Candidate Molecular
Mechanism for the Association of an Intronic Polymorphism of FE65 with Resistance to
Very-Late Onset Dementia of the Alzheimer Type. Human Molecular Genetics 11: 465-475,
2002.
19. Jin LW, Hua DH, Shie FS, Maezawa I, Sopher B, Martin GM. Novel tricyclic pyrone
compounds prevent intracellular APP C99-induced cell death. J Mol Neurosci 19:57-61,
2002.
20. Martin, G.M. The Evolutionary Substrate of Aging. Archives of Neurology 59: 1702-1705,
2003.
21. Wang B, Hu Q, Hearn MG, Shimizu K, Ware CB, Liggitt DH, Jin LW, Cool BH, Storm DR,
Martin GM. Isoform-specific knockout of FE65 leads to impaired learning and memory. J
Neurosci Res. 75:12-24, 2004.
22. Martin GM. Genetic modulation of senescent phenotypes in Homo sapiens. Cell 120 (4):
523-532, Feb 25 2005.
23. Hu Q., Wang L., Yang Z., Cool B.H., Zitnik G., Martin G.M. “Endoproteolytic cleavage of
FE65 converts the adaptor protein to a potent suppressor of the sAPPalpha pathway in
primates.” J Biol Chem 280: 12548-12558, 2005.
24. Martin G.M. “Genetic modulation of senescent phenotypes in Homo sapiens.” Cell 120: 523532, Feb 25 2005.
25. Schriner S.E., Linford N.J., Martin G.M., Treuting P., Ogburn C.E., Emond M., Coskun P.E.,
Ladiges W., et al. “Extension of murine lifespan by overexpression of catalase targeted to
mitochondria.” Science 308: 1909-1911, 2005.
26. Martin G.M. “Epigenetic drift in aging identical twins.” PNAS 102: 10413-10414, 2005.
27. Wolf N., Penn P., Pendergrass W., Van Remmen H., Bartke A., Rabinovitch P., Martin G.M.
“Age-related cataract progression in five mouse models for anti-oxidant protection or
hormonal influence.” Experimental Eye Research 81: 276-285, 2005.
28. Huang S., Chen L., Libina N., Janes J., Martin G.M., Campisi J., Oshima J. “Correction of
cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference.” Hum Genet
118:444-50, 2005.
29. Loeb L.A., Wallace D.C., Martin G.M. “The mitochondrial theory of aging and its relationship
to reactive oxygen species damage and somatic mtDNA mutations.” PNAS 102:18769-70,
2005.
30. Martin G.M. “Genetic engineering of mice to test the oxidative damage theory of aging.” Ann
NY Acad Sci 1055:1-9, Dec 2005.
31. Cutler R., Guarante L.P., Kensler T.W., Naftolin F., Jones D.P., Cantor C.R., Martin G.M.
“Longevity determinant genes: what is the evidence? What's the importance? Panel
discussion.” Ann N Y Acad Sci 2005 Dec;1055:58-63.
32. Yang Z., Cool B.H., Martin G.M., Hu Q. “A dominant role for FE65 (APBB1) in nuclear
signaling.” J Biol Chem 281(7):4207-14, 17 Feb 2006.
33. Martin G.M. “Keynote lecture: an update on the what, why and how questions of ageing.”
Exp Gerontol 2006 May;41(5):460-3.
34. Huang S., Lee L., Hanson N.B., Lenaerts C., Hoehn H., Poot M., Rubin C.D., Chen D.F. et
al. “The spectrum of WRN mutations in Werner syndrome patients.” Hum Mutat 2006
Jun;27(6):558-67.
35. Maezawa I., Hong H.S., Wu H.C., Battina S.K., Rana S., Iwamoto T., Radke G.A.,
Pettersson E., et al. “A novel tricyclic pyrone compound ameliorates cell death associated
with intracellular amyloid-beta oligomeric complexes.” J Neurochem 2006 Jul;98(1):57-67.
36. Martin, G.M., Kennedy, D. “SAGE lessons.” Science. 2006 Jul;313(5783):17.
37. Martin, G.M. “The genetics and epigenetics of altered proliferative homeostasis in ageing
and cancer.” Mech Ageing Dev. 2007 Jan;128(1):9-12.
38. Nguyen, D., Leistritz, D.F., Turner, L., Macgregor, D., Ohson, K., Dancey, P., Martin, G.M.,
Oshima, J. “Collagen expression in fibroblasts with a novel LMNA mutation.” Biochem
Biophys Res Commun. 2007 Jan 19;352(3):603-8.
39. Martin, G.M. "Premature Aging." Encyclopedia of Gerontology (Second Edition): Age, Aging,
and the Aged. Elsevier Inc. 2:379-384, 2007.
40. Shao, J., Chen, L., Marrs, B., Lee, L., Huang, H., Manton, K.G., Martin, G.M., Oshima, J.
“SOD2 polymorphisms: Unmasking the effect of polymorphism on splicing.” BMC Med
Genet. 2007 Mar 1;8(1):7.
41. Zitnik, G., Wang, L., Martin, G.M., Hu, Q. “Localizations of endogenous APP/APP-proteolytic
products are consistent with microtubular transport.” J Mol Neurosci. 2007;31:59-68.
42. Martin, G.M. “Modalities of gene action predicted by the classical evolutionary biological
theory of aging.” Ann NY Acad Sci. 2007 Apr;1100:14-20.
43. Martin, G.M., Bergman, A., Barzilai, N. “Genetic determinants of human health span and life
span: progress and new opportunities.” PloS Genet. 2007 Jul 27;3(7):e125.
44. Martin, G.M. “Clonal attenuation of somatic cells in aging mammals: a review of supportive
evidence and its biomedical significance.” Ann N Y Acad Sci. 2007 Dec;1119:1-8. Epub
2007 Aug 23.
45. Huang, S., Risques, R.A., Martin, G.M., Rabinovitch, P.S., Oshima J. “Accelerated telomere
shortening and replicative senescence in human fibroblasts overexpressing mutant and
wild-type lamin” A. Exp Cell Res. 2008 Jan 1;314(1):82-91. Epub 2007 Aug 16.
46. Martin, G.M., Lederberg J. “The Biology of Aging: Current Research and Expected Future
Gains.” Global Health and Global Aging. 249-256. Eds. Robinson M, Novelli W, Pearson C,
Norris L. Jossey-Bass. 2007.
47. Kulminski, A.M., Ukraintseva, S.V., Arbeev, K.G., Manton, K.G., Oshima, J., Martin, G.M.,
Il'yasova, D., Yashin, A.I. “Health-Protective and Adverse Effects of the Apolipoprotein E
epsilon2 Allele in Older Men.” J Am Geriatr Soc. 2008 Jan 4; [Epub ahead of print]
48. Kulminski, A.M., Ukraintseva, S.V., Arbeev, K.G., Manton, K.G., Oshima, J., Martin, G.M.,
Yashin, A.I. “Association between APOE epsilon 2/epsilon 3/epsilon 4 polymorphism and
disability severity in a national long-term care survey sample.” Age and Ageing. 2008 Feb 4;
[Epub ahead of print]
49. Butler, R.N., Miller, R.A., Perry, D., Carnes, B.A., Williams, T.F., Cassel, C., Brody, J.,
Bernard, M.A., Partridge, L., Kirkwood, T., Martin, G.M., Olshansky, S.J. “New model of
health promotion and disease prevention for the 21st century.” BMJ. 2008 Jul 8;337:a399.
50. Treuting, P.M., Linford, N.J., Knoblaugh, S.E., Emond, M.J., Morton, J.F., Martin, G.M.,
Rabinovitch, P.S., Ladiges, W.C. “Reduction of age-associated pathology in old mice by
overexpression of catalase in mitochondria.” J Geron Biol Sci. 2008 Aug; 63(8): 813-824.
51. Martin, G.M., “Modalities of Gene Action Predicted by the Classical Evolutionary Theory of
Aging.” Handbook of Theories of Aging. 226-250. Eds. Bengston V, Silverstein M, Norella
P, Gans D. 2008.
52. Dai, D, Santana, L.F., Vermulst, M., Tomazela, D.M., Emond, M.J., MacCoss, M.J.,
Gollahon, K., Martin, G.M., Loeb, L.A., Ladiges, W.C., Rabinovitch, P.S. “Overexpression of
catalase targeted to mitochondria attenuates murine cardiac aging.” Circulation Research.
2009 Jun; 119(21): 2789-U79.
53. Martin, G.M., “The 2008 American Federation For Aging Annual Research Conference:
Aging and Cancer: Two Sides of the Same Coin?” Journal of Gerontology Series ABiological Science and Medical Sciences. 2009 Jun; 64A (6): 615-617.
54. Wang, Y., Zhang, M., Moon, C., Hu, Q., Wang, B., Martin, G.M., Sun, Z., Wang, H., “The
APP-interacting protein FE65 is required for hippocampus-dependent learning and longterm potentiation.” Learning Memory. 2009 Aug; 16(9): 537-44.
55. Martin, G.M. “Epigenetic gambling and epigenetic drift as an antagonistic pleiotropic
mechanism of aging.” Aging Cell. 2009 Dec; 8(6):761-4.
56. Cool, B.H., Zitnik, G., Martin, G.M., Hu, Q. “Structural and functional characterization of a
novel FE65 protein product up-regulated in cognitively impaired FE65 knockout mice.” J
Neurochem 2010 Jan; 112(2):410-9.
57. Cool, B.H., Chan, G.C., Lee, L., Oshima, J., Martin, G.M., Hu, Q. “A flanking gene problem
leads to the discovery of a Gprc5b splice variant predominantly expressed in C57B1/6J
mouse brain and in maturing neurons.” PloS One. 2010 Apr 26; 5(4): e10351.
58. Rae, M.J., Butler, R.J., Campisi, J., et al., “The Demographic and Biomedical Case for LateLife Interventions in Aging.” Science Translational Medicine. 2010 Jul 2010; 40cm21
59. Friedrich, K., Lee, L., Leistritz, D.F., Nurnberg, G., Saha, B., Hisama, F.M., Eyman, D.K.,
Lessel, D., et al.“WRN mutations in Werner syndrome patients: genomic rearrangements,
unusual intronic mutations and ethnic-specific alterations.” Human Genetics. 2010
Jul;128(1):103-11.
60. Risques, R.A., Arbeev, K.G., Yashin, A.I., Ukraintseva, S.V., Rabinovitch, P.S., Martin, G.M.,
Oshima, J. “Leukocyte Telomere Length Is Associated with Disability in Older U.S.
Population.” J Amer Geriatr Soc. 2010 Jul;58(7):1289-98.
61. Saha B, Lessel D, Hisama FM, Leistritz DF, Friedrich K, Martin, G.M., Oshima, J. “A novel
LMNA mutation causes altered nuclear morphology and symptoms of familial partial
lipodystrophy (Dunnigan Variety) with progeroid features.” Mol Syndromology (2010) Sep;
1(3):127-132.
62. Cool, B.H., Chan, G.C., Lee, L., Oshima, J., Martin, G.M., and Hu, Q. "A Flanking Gene
Problem Leads to the Discovery of a Gprc5b Splice Variant Predominantly Expressed in
C57Bl/6J Mouse Brain and in Maturing Neurons." PloS One (2010) April 26; 5(4): e10351.
63. Rae MJ, Butler RN, Campisi J, De Grey AD, Finch CE, Gough M., Martin GM, et al. "The
Demographic and Biomedical Case for Late-life Interventions in Aging." Science
Translational Medicine (2010) 2(40): 40.
64. Martin G.M., “The biology of aging: 1985-2010 and beyond.” FASEB J. (2011) Nov;
25(11):3756-62.
65. Martin G.M., “The Science: Then and Now.” American Federation For Aging Research.
(2011)
66. Hisama FM, Lessel D, Leistritz D, Friedrich K, McBride K, Pastore M., Gottesman GS, Saha
B, Martin GM, Kubisch C, Oshima J, “Coronary Artery Disease in a Werner Syndrome-like
Form of Progeria Characterized by Low Levels of Progerin, a Splice Variant of Lamin A.”
American Journal of Medical Genetics (2011) Dec; 155A(12): 3002-6.
67. Martin, G.M., “Commentary: A gerontological perspective on Klaus Gärtner's discovery that
phenotypic variability of mammals is driven by stochastic events.” International Journal of
Epidemiology (2012).
68. Hisama, F., Oshima, J., Kubisch, C., Martin, G.M. “Clinical utility gene card for: Werner
syndrome.” European Journal of Human Genetics (2012).
69. Martin, G.M., “Lecture Presentation: Epigenetic gambling & epigenetic drift as potential
mechanisms underlying the quasi-stochastic distributions of late life neurodegenerative
disorders.” Molecular Neurodegeneration (2012).
70. Martin GM, “Stochastic Modulations of the Pace and Patterns of Ageing: Impacts on QuasiStochastic Distributions of Multiple Geriatric Pathologies.” Mechanisms of Ageing and
Development (2012) April; 133(4): 107-11.
71. Saha B., Lessel D., Nampoothiri S., Rao A.S., Dincy P., Bennett C., Nürnberg G., Nürnberg
P., Hisama F.M., Martin, G.M., Kubisch C., Oshima J. “Ethnic specific WRN mutations in
South Asian Werner syndrome patients: Potential founder effect in patients with Indian or
Pakistani ancestry.” Molecular Genetics & Genomic Medicine (2013) May 1; 1(1):7-14.
72. Alarcón MA, Medina MA, Hu Q, Avila ME, Bustos BI, Perez-Palma E, Peralta A, Salazar P,
Ugarte GD, Reyes AE, Martin GM, Opazo C, Moon RT, De Ferrari GV, “A novel functional
low-density lipoprotein receptor-related protein 6 gene alternative splice variant is
associated with Alzheimer’s disease.” Neurobiology Aging (2013) June; 34(6): 1709.e9-18.
73. Saha B, Zitnik G, Johnson S, Nguyen Q, Risques RA, Martin GM, Oshima J, “ DNA damage
accumulation and TRF2 degradation in atypical Werner syndrome fibroblasts with LMNA
mutations.” Frontiers in Genetics of Aging (2013) July 5; 4: 129.
74. Johnson SC, Martin GM, Rabinovitch PS, Kaeberlein M. “Preserving Youth: Does
Rapamycin Deliver?” Science Translational Medicine (2013) Nov 13; 5(211):211fs40..
75. Saha B, Cypro A, Martin GM, Oshima J. “Rapamycin decreases DNA damage accumulation
and enhances cell growth of WRN deficient human fibroblasts.” Aging Cell (2014) June;
13(3):573-5.
76. Lessel D, Saha B, Hisama F, Kaymakamzade B, Nurlu G, Gursoy-Özdemir Y, Thiele H,
Nümberg P, Martin GM, Kubuisch C, Oshima J. “Atypical Aicardi-Goutieres syndrome: Is the
WRN locus a modifier?” American Journal of Medical Genetics (2014) July; Part A. 9999:1–
4.
77. Oshima J, Martin GM, Hisama, F. “An encouraging progress report on the treatment of
progeria and its implications for atherogenesis.” Circulation (2014). In press.
78. Hisama F, Kubisch C, Martin GM, Oshima J. “CUGC-Werner Syndrome.” European Journal
of Human Genetics (2014). In press.