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Training Grant-
Biology of Aging

Craig Atwood

Craig S. Atwood

Ph.D., University of Western Australia, Perth
Associate Professor, Department of Medicine- Geriatrics & Gerontology
Research Director, Laboratory for Endocrinology, Aging and Disease

Hormonal Regulation of Aging and Neurodegenerative Diseases

My research interests relate to the endocrinology of aging as elaborated upon in 'The Reproductive-Cell Cycle Theory of Aging'. The basic premise to the theory is that hormones that regulate reproduction in mammals act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence (Bowen and Atwood, 2004, Gerontology). To this end, we have demonstrated that the age-related increase in luteinizing hormone and decline in sex steroids is directly responsible, via mechanisms related to the aberrant re-entry of post-mitotic neurons into the cell cycle, for the age-related increase in the incidence of Alzheimer's disease. Recent data suggests similar mechanisms are responsible for stroke. I have broad research interests related to the endocrinology of embryogenesis, adulthood and senescence. More recently my laboratory has utilized human embryonic stem cells in vitro as a model system for delineating the hormonal and molecular basis of early human embryogenesis and neurogenesis, as well as for understanding neurodegeneration associated with age-related neurological diseases such as Alzheimer's disease. Our research aims to identify and implement therapeutics to delay the onset or slow the progression of senescence and aging-related diseases like Alzheimer's disease through the manipulation of HPG axis hormones.

Representative Publications
Atwood, C.S., Hayashi, K., Vadakkadath Meethal, S., Gonzales, T., & Bowen, R.L. (2017). Does the degree of endocrine dyscrasia post-reproduction dictate post-reproductive lifespan? Lessons from semelparous and iteroparous species. Geroscience, 39(1), 103-116. Advanced online publication.
View publication via DOI: DOI:10.1007/s11357-016-9955-5

Geddes, R. I., Hayashi, K., Bongers, Q., Wehber, M., Anderson, I. M., Jansen, A. D., ... Atwood, C. S. (2017). Conjugated linoleic acid administration induces amnesia in male sprague dawley rats and exacerbates recovery from functional deficits induced by a controlled cortical impact injury. PLoS One, 12(1), e0169494.
View publication via DOI: DOI:10.1371/journal.pone.0169494

Gonzales, T. K., Yonker, J. A., Chang, V., Roan, C. L., Herd, P., & Atwood, C. S. (2017). Myocardial infarction in the Wisconsin longitudinal study: The interaction among environmental, health, social, behavioural and genetic factors. BMJ Open, 7(1), e011529.
View publication via DOI: DOI:10.1136/bmjopen-2016-011529

Hoscheidt, S. M., Starks, E. J., Oh, J. M., Zetterberg, H., Blennow, K., Krause, R. A., ... Puglielli, L., Atwood, C. S., ... Asthana, S., Johnson, S. C., & Bendlin, B. B. (2016). Insulin resistance is associated with increased levels of cerebrospinal fluid biomarkers of Alzheimer's disease and reduced memory function in at-risk healthy middle-aged adults. Journal of Alzheimer's Disease, 52(4), 1373-1383.
View publication via DOI: DOI:10.3233/jad-160110

Atwood, C. S., & Vadakkadath Meethal, S. (2016). The spatiotemporal hormonal orchestration of human folliculogenesis, early embryogenesis and blastocyst implantation. Molecular and Cellular Endocrinology, 430, 33-48.
View publication via DOI: DOI:10.1016/j.mce.2016.03.039

Bowen, R. L., Butler, T., & Atwood, C. S. (2016). Not all androgen deprivation therapies are created equal: Leuprolide and the decreased risk of developing Alzheimer's disease. Journal of Clinical Oncology, 34(23), 2800.
View publication via DOI: DOI:10.1200/jco.2015.66.3997

Bowen, R.L., Perry, G., Xiong, C., Smith, M.A., & Atwood, C.S. (2015). A clinical study of Lupron Depot in the treatment of women with Alzheimer's Disease: Preservation of cognitive function in patients taking an acetylcholinesterase inhibitor and treated with high dose Lupron over 48 weeks. Journal of Alzheimer's Disease, 44(2), 549-560.
View publication via DOI: DOI:10.3233/JAD-141626

Gleason, C. E., Fischer, B. L., Dowling, N. M., Setchell, K. D., Atwood, C. S., Carlsson, C. M., & Asthana, S. (2015). Cognitive effects of soy isoflavones in patients with Alzheimer's disease. Journal of Alzheimer's Disease, 47(4), 1009-1019.
View publication via DOI: DOI:10.3233/jad-142958

Gleason, C. E., Dowling, N. M., Wharton, W., Manson, J. E., Miller, V. M., Atwood, C. S., ... Asthana, S. (2015). Effects of hormone therapy on cognition and mood in recently postmenopausal women: Findings from the randomized, controlled keeps-cognitive and affective study. PLoS Med, 12(6), e1001833.
View publication via DOI: DOI:10.1371/journal.pmed.1001833

Atwood, C. S., & Bowen, R. L. (2015). A unified hypothesis of early- and late-onset Alzheimer's disease pathogenesis. Journal of Alzheimer's Disease, 47(1), 33-47.
View publication via DOI: DOI:10.3233/jad-143210

Atwood, C. S., & Bowen, R. L. (2015). The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease. Hormones and Behavior, 76, 63-80.
View publication via DOI: DOI:10.1016/j.yhbeh.2015.06.021

Yonker, J.A., Chang, V., Roetker, N.S., Hauser, T.S., Hauser, R.M., & Atwood, C.S. (2013). Hypothalamic-pituitary-gonadal axis homeostasis predicts longevity. Age, 31(1), 129-138.
View publication via DOI: DOI:10.1007/s11357-011-9342-1

Roetker, N. S., Page, C. D., Yonker, J. A., Chang, V., Roan, C. L., Herd, P., . . . Atwood, C. S. (2013). Assessment of genetic and nongenetic interactions for the prediction of depressive symptomatology: An analysis of the Wisconsin Longitudinal Study using machine learning algorithms. American Journal of Public Health, 103 Suppl 1, S136-144.
View publication via DOI: DOI:10.2105/ajph.2012.301141

Vadakkadath Meethal, S., & Atwood, C.S. (2012). Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis. Neurobiology of Aging, 33(3), 569-581.
View publication via DOI: DOI:10.1016/j.neurobiolaging.2010.04.012

Chabris, C.F., Hebert, B.M., Benjamin, D.J., Beauchamp, J., Cesarini, D., van der Loos, M., ... Atwood, C.S., .. Laibson, D. (2012). Most reported genetic associations with general intelligence are probably false positives. Psychological Science, 23(11), 1314-1323.
View publication via DOI: DOI:10.1177/0956797611435528

Roetker, N.S., Yonker, J.A., Lee, C., Chang, V., Basson, J., Roan, C.L., ... Atwood, C.S. (2012). Multi-gene interactions and the prediction of depression in the Wisconsin Longitudinal Study. BMJ Open, 2, e000944.
View publication via DOI: DOI:10.1136/bmjopen-2012-000944.

Clark, I.A., & Atwood, C.S. (2011). Is TNF a link between aging-related reproductive endocrine dyscrasia and Alzheimer's disease? Journal of Alzheimer's Disease, 27(4), 691-699.
View publication via DOI: DOI:10.3233/JAD-2011-110887

Gallego, M.J., Porayette, P., Kaltcheva, M.M., Bowen, R.L., Vadakkadath Meethal, S., & Atwood, C. S. (2010). The pregnancy hormones human chorionic gonadotropin and progesterone induce human embryonic stem cell proliferation and differentiation into neuroectodermal rosettes. Stem Cell Research & Therapy, 1(28).
View publication via DOI: DOI:10.1186/scrt28

Xu, G., McLaren, D.G., Ries, M.L., Fitzgerald, M.E., Bendlin, B.B., Rowley, H.A., Sager, M.A., Atwood, C.S., Asthana, S., & Johnson, S.C. (2009). The influence of parental history of Alzheimer's disease and apolipoprotein E 4 on the BOLD signal during recognition memory. Brain, 132, 383-391.
View publication via DOI: DOI:10.1093/brain/awn254

Gallego, M.J., Porayette, P. Kaltcheva, M.M., Meethal, S.V., & Atwood, C.S. (2009). Opioid and progesterone signaling is obligatory for early human embryogenesis. Stem Cells and Development. 18(5), 737-740.
Click here to download this publication.
View publication via DOI: DOI:10.1089/scd.2008.0190

Gleason, C.E., Carlsson, C.M., Barnet, J.H., Meade, S.A., Setchell, K.D., Atwood, C.S., Johnson, S.C., Ries, M.L., & Asthana, S. (2009). A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women. Age and Ageing, 38(1), 86-93.
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View publication via DOI: DOI:10.1093/ageing/afn227

Meethal, S.V., Liu, T., Chan, H., Ginsburg, E., Wilson, Gray, D.N., Bowen, R.L., Vonderhaar, B.K., & Atwood, C.S. (2009). Identification of a regulatory loop for the synthesis of neurosteroids: A StAR-dependent mechanism involving HPG axis receptors. Journal of Neurochemistry, 110, 1014-1027.
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View publication via DOI: DOI:10.1111/j.1471-4159.2009.06192.x

Porayette, P., Gallego, M.J., Kaltcheva, M.M., Bowen, R.L., Meethal, S.V., & Atwood, C.S. (2009). Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells. Journal of Biological Chemistry, 284(35), 23806-23817.
View publication via DOI: DOI:10.1074/jbc.M109.026328

Siedlak, S., Casadesus, G., Webber, K.M., Pappolla, M.A., Atwood, C.S., Smith, M.A., & Perry, G. (2009). Chronic antioxidant therapy reduces oxidative stress in a mouse model of alzheimer disease. Free Radical Research, 43(2), 156-164.
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View publication via DOI: DOI:10.1080/10715760802644694

Simon, D., Meethal, S.V., Wilson, A.C., Gallego, M.J., Weinecke, S.L., Bruce, E., Lyons, P.F., Haasl, R.J., Bowen, R.L., & Atwood, C.S. (2009). Activin receptor signaling regulates prostatic epithelial cell adhesion and viability. Neoplasia, 11(4), 365-376.
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View publication via DOI: DOI:10.1593/neo.81544

Atwood, C.S., & Bowen, R.L. (2008). A multi-hit endocrine model of intrinsic adult-onset asthma. Ageing Research Reviews, 7(2), 114-125.
View publication via DOI: DOI:10.1016/j.arr.2007.12.002

Chan, H.W., Liu, T., Verdile, G., Bishop, G.M., Haasl, R.J., Smith, M.A., Perry, G., Martins, R.N., & Atwood, C.S. (2008). Copper induces apoptosis of neuroblastoma cells via post-translational regulation of the expression of Bcl-2-family proteins and the txJ mouse is a better model of hepatic than brain Cu toxicity. International Journal of Clinical and Experimental Medicine, 1, 76-86.

Gonzalez-Cuyar, L.F., Perry, G., Miyajima, H., Atwood, C.S., Riveros-Angel, M., Lyons, P.F., Siedlak, S.L., Smith, M.A., & Castellani, R.J. (2008). Redox active iron accumulation in aceruloplasminemia. Neuropathology, 8(5),466-471.
View publication via DOI: DOI:10.1111/j.1440-1789.2008.00901.x

Haasl, R.J., Reza Ahmadi, M., Vadakkadath Meethal, S., Gleason, C.E., Johnson, S.C., Asthana, S., Bowen, R.L., & Atwood, C.S. (2008). A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer's disease in males carrying an apolipoprotein E e4 Allele. BMC Medical Genetics, 9(1), 37.
View publication via DOI: DOI:10.1186/1471-2350-9-37

Rodrigues, M.A., Verdile, G., Foster, J.K., Hogervorst, E., Joesbury, K., Dhaliwal, S., Corder, E.H., Laws, S.M., Hone, E., Prince, R., Devine, A., Mehta, P., Beilby, J., Atwood, C.S., & Martins, R.N. (2008). Gonadotropins and cognition in older women. Journal of Alzheimer's Disease, 13(3), 267-274.

Wilson, A.C., Clemente, L., Liu, T., Bowen, R.L., Vadakkadath Meethal, S., & Atwood, C.S. (2008). Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1782(6), 401-7.
View publication via DOI: DOI:10.1016/j.bbadis.2008.02.011

Friedland, R.P., Tedesco, J., Wilson, A.C., Atwood, C.S., Smith, M.A., Perry, G., Zagorski, M.G. (2008). Antibodies to potato virus Y bind the A-beta protein: Immunohistochemical and NMR studies. Journal of Biological Chemistry, 283(33), 22550-22556.
View publication via DOI: DOI:10.1074/jbc.M802088200

Gallego, M.J., Porayette, P., Kaltcheva, M.M., Vadakkadath Meethal, S., & Atwood, C.S. (2008). Opioid and progesterone signaling is obligatory for early human embryogenesis. Stem Cells and Development, 18(5), 737-740.
View publication via DOI: DOI:10.1089/scd.2008.0190

Carlsson, C.M., Gleason, C.E., Hess, T.M., Moreland, K.A., Blazel, H.M., Koscik, R.L., Schreiber, N.T.N., Johnson, S.C., Atwood, C.S., Puglielli, L., Hermann, B.P., McBride, P.E., Stein, J.H., Sager, M.A., & Asthana, S. (2008). Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimers disease. Journal of Alzheimers Disease, 13(2), 187-97.

Trivedi, M.A., Schmitz, T.W., Ries, M.L., Hess, T.M., Fitzgerald, M.E., Atwood, C.S., Rowley, H.A., Asthana, S., Sager, M.A., & Johnson, S.C. (2008). fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: Risk factors for Alzheimer's disease. Neuropsychologia, 46(6), 1667-1678.
View publication via DOI: DOI:10.1016/j.neuropsychologia.2007.11.035

Bishop, G.M., Smith, M.A., LaManna, J.C., Wilson, A.C., Perry, G., & Atwood, C.S. (2007). Iron homeostasis is maintained in the brain, but not the liver, following mild hypoxia. Redox Report, 12(6), 257-266.
View publication via DOI: DOI:10.1179/135100007X239270

Liu, T., Wimalasena, J., Bowen, R.L., & Atwood, C.S. (2007). Luteinizing hormone receptor mediates neuronal pregnenolone production via upregulation of steroidogenic acute regulatory protein expression. Journal of Neurochemistry, 100(5), 1329-1339.
View publication via DOI: DOI:10.1111/j.1471-4159.2006.04307.x

Porayette, P., Gallego, M.J., Kaltcheva, M.M., Vadakkadath Meethal, S., & Atwood, C.S. (2007). Amyloid-b precursor protein expression and modulation in human embryonic stem cells: A novel role for human chorionic gonadotropin. Biochemical and Biophysical Research Communications, 364(3), 522-527.
View publication via DOI: DOI:10.1016/j.bbrc.2007.10.021

Wung, J.K., Perry, G., Kowalski, A.., Harris, P.L.R., Bishop, G.M., Trivedi, M.A., Johnson, S.C., Smith, M.A., Denhardt, D.T., & Atwood, C.S. (2007). Increased expression of the remodeling- and tumorigenic-associated factor osteopontin in pyramidal neurons of the alzheimer's disease brain. Current Alzheimer Research, 4(1), 67-72.
View publication via DOI: DOI:10.2174/156720507779939869

Gleason, C.E., Carlsson, C.M., Johnson, S.C., Atwood, C., & Asthana, S. (2005). Clinical pharmacology and differential cognitive efficacy of estrogen preparations. Annals of the New York Academy of Science, 1052, 93-115.
View publication via DOI: DOI:10.1196/annals.1347.007

Atwood, C.S., Perry, G., Zeng, H., Kato, Y., Jones, W.D., Huang, X., Chen, S., Sayre, L.M., Ling, K.-Q., Smith M.A., & Bush, A.I. (2004). Copper mediates dityrosine cross-linking of Alzheimer's amyloid-β. Biochemistry, 43(2), 560-568.
View publication via DOI: DOI:10.1021/bi0358824

Liu, T., Perry, G., Chan, H.W., Verdile, G., Martins, R.N., Smith, M.A., & Atwood, C.S. (2004). Amyloid-β-induced toxicity of primary neurons is dependent upon differentiation associated increases in tau and cyclin-dependent kinase 5. Journal of Neurochemistry, 88(3), 554-563.
View publication via DOI: DOI:10.1046/j.1471-4159.2003.02196.x

Bowen, R.L., Verdile, G., Liu, T., Parlow, A.F., Perry, G., Smith, M.A., Martins, R.N., & Atwood, C.S. (2004). Luteinizing Hormone, a Reproductive Regulator that Modulates the Processing of Amyloid-beta Precursor Protein and Amyloid-beta Deposition. J. Biol. Chem, 279, 20539 - 20545.
View publication via DOI: DOI:10.1016/j.bbadis.2006.01.008

Bowen, R.L. and Atwood, C.S. (2004). Living and Dying for Sex: A theory of aging based on the modulation of cell cycle signaling by reproductive hormones. Gerontology, 50(5), 265-290.
View publication via DOI: DOI:10.1159/000079125

Veurink, G., Liu, D., Taddei, K., Perry, G., Smith, M.A., Robertson, T.A., Hone, E., Groth, D.M., Atwood, C.S., & Martins, R.N. (2003). Reduction of inclusion body pathology in Apo-E-deficient mice fed a combination of antioxidants. Free Radicals in Biology and Medicine, 34(8), 1070-1077.
View publication via DOI: DOI:10.1016/S0891-5849(03)00042-X

Dong, J., Atwood, C.S., Anderson, V.E., Siedlak, S.L., Smith, M.A., Perry, G., & Carey, P.R. (2003). Metal binding and oxidation of amyloid-β within isolated senile plaque cores: Raman microscopic evidence. Biochemistry, 42(10), 2768-2773.
View publication via DOI: DOI:10.1021/bi0272151

Atwood, C.S., Barzilai, N., Bowen, R.L., Brown-Borg, H.M., Jarrard, D.F., Fu, V.X., Heilbronn, L.K., Ingram, D.K., Ravussin, E., Schwartz, R.S., & Weindruch, R. (2003). Pennington scientific symposium on mechanisms and retardation of aging. Experimental Gerontology, 38(10), 1217-1226.
View publication via DOI: DOI:10.1016/j.exger.2003.08.005

Bowen, R.L., Smith, M.A., Harris, P.L.R., Kubat, Z., Martins R.N., Castellani, R.J., Perry, G., & Atwood, C.S. (2002). Elevated luteinizing hormone expression colocalizes with neurofibrillary tangles in Alzheimer disease. Journal of Neuroscience Research, 70(3), 514-518.
View publication via DOI: DOI:10.1002/jnr.10452

Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A. Barnham, K.J., Volitakis, I., Fraser, F.W., Kim, Y.-S., Huang, X., Goldstein, L.E., Moir, R.D., Lim, J.T., Beyreuther, K.T., Zheng, H., Tanzi, R.E., Masters, C.L., & Bush, A. (2001). Treatment of a copper-zinc chelator markedly and rapidly inhibits β-Amyloid accumulation in Alzheimer disease transgenic mice. Neuron, 30, 665-676.
View publication via DOI: DOI:10.1016/S0896-6273(01)00317-8

Atwood, C.S., Hovey, R., Glover, J.P., Chepko, G., Ginsburg, E., Robison, Jr., W.G., & Vonderhaar, B.K. (2000). Progesterone induces ductal side-branching of the ductal epithelium in the mammary glands of peripubertal mice. Journal of Endocrinology, 167, 39-52.
View publication via DOI: DOI:10.1677/joe.0.1670039

Atwood, C.S., Scarpa, R.C., Huang, X., Moir, R.D., Jones, W.D., Fairlie, D.P., Tanzi, R.E., & Bush, A.I. (2000). Characterization of copper interactions with Alzheimer amyloid beta peptides: Identification of an attomolar-affinity copper binding site on amyloid beta1-42. Journal of Neurochemistry, 75, 1219-1233.
View publication via DOI: DOI:10.1046/j.1471-4159.2000.0751219.x

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