Keywords:

aging, life span, longevity, growth hormone, prolactin, dwarf mouse, oxidative stress, catalase, superoxide dismutase, glutathione peroxidase, mitochondria, oxidative damage, neuroendocrinimmunology

Education/Training:

• Research Associate, Physiology, Southern Illinois University
• Research Associate, Endocrinology, USDA ARS MARC
• Ph.D., Physiology, North Carolina State University
• M.S., Animal Science, University of Nebraska-Lincoln

Research Description:

A popular theory to explain the physiological decline that occurs during aging involves oxidative stress and subsequent damage to DNA, proteins and lipids. Delaying this decline is associated with extended life span. Mice with hereditary dwarfism (Ames dwarf, df/df) and growth hormone (GH) deficiency exhibit delayed aging, living more than a year longer than normal siblings (P<0.0001), differences in antioxidant defense capacity and lower DNA damage. In contrast, mice with high plasma GH concentrations live half as long as normal, wild type siblings and exhibit a depressed antioxidative defense capacity. The overall hypothesis is that the Ames dwarf mouse has a biologic advantage over normal wild type mice with better enzymatic scavenging of toxic metabolic byproducts and less mitochondrial membrane leakage underlying their enhanced longevity. Our current studies are designed to further understand the relationship between cellular oxidation, hormones, mitochondrial activities and aging in a mammalian model of extended life span. Determining the pathways and mechanisms that GH utilizes may suggest potential therapeutic interventions that could lead to strategies to delay aging, treat aging-related disorders and extend life span in humans

Selected Publications:

• Brown-Borg, H.M. 2008. Hormonal control of aging in rodents: The somatotropic axis. Molecular and Cellular Endocrinology (in press).
• Brown-Borg, H.M., S. G. Rakoczy, S. Sharma and A. Bartke. 2008. Long-living growth hormone receptor knock out
  mice: potential mechanisms of altered stress resistance. Experimental Gerontology (in press).
• Dhanasekaran, M., S.S. Karuppagounder, S. Uthayathas, L. Wold, K. Parameshwaran, J. Babu, V. Suppiramaniam and H.Brown-Borg. 2008. Effect of dopaminergic neurotoxin MPTP/MPP+ on coenzyme Q content. Life Sciences (in press).
• Chen, C.-n., H.M. Brown-Borg, S.G. Rakoczy, L.V. Thompson. 2008. Muscle disuse: adaptation of antioxidant
  systems is age-dependent. J Gerontology: Biological Sciences 63A(5):461-466.
• Shavali, S., H.M. Brown-Borg, M. Ebadi and J. Porter. 2008. Mitochondrial localization of alpha- synuclein protein in
  alpha-synuclein-overexpressing cells. Neuroscience Letters 439(2):125-128.
• Dhanasekaran, M., C.B. Albano, L. Pellet, S.S. Karuppagounder, S. Uthayathas, V. Suppiramaniam, H.M. Brown-Borg, M. Ebadi. 2008. Role of lipoamide dehydrogenase and metallothionein on 1- methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced toxicity. Neurochemical Research 33(6):980-984.
• Schrag, M., S. Sharma, H.M. Brown-Borg and O. Ghribi. 2008. Hippocampus of Ames dwarf mice is resistant to beta-amyloid-induced tau hyperphosphorylation and changes in apoptosis-regulatory protein levels. Hippocampus 18(3):239-244.
• Brown-Borg, H.M. 2007. Hormonal regulation of longevity in mammals. Ageing Research Reviews 6(1):28-45.
• Brown-Borg, H.M. 2006. Longevity in mice: Is stress resistance a common factor? AGE 28:145-162.
• Dhanasekaran, M., S. Uthayathas, S.S. Karuppagounder, K. Parameshwaran, V. Suppiramaniam, M. Ebadi and H.M. Brown-Borg. 2006. Ebselen effects on MPTP-induced neurotoxicity. Brain Research 1118:251-254.
• Ebadi, M., H.M. Brown-Borg, S. Sharma, S. Shavali and M. Ioudina. 2006. Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases. Current Drug Targets 7:1513-1529.
• Uthus, E.O., and H.M. Brown-Borg. 2006. Methionine flux to transulfuration is enhanced in the long living Ames dwarf mouse. Mechanisms of Ageing & Development 127:444-450.
• Corton, J.C., and H.M. Brown-Borg. 2006. Peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1) in caloric restriction and other models of longevity. J. Gerontology: Biological Sciences 60A (12):1494-1509.
• Johnson, W.T., and H.M. Brown-Borg. 2006. Cytochrome c oxidase deficiency occurs in cardiac mitochondria during late postnatal heart development in progeny of copper-deficient dams.Experimental Biology and Medicine 231:172-180.
• Tharakan, B., D. Muralikrishnan, H.M. Brown-Borg and B.V. Manyam. 2005. Trichopus zeylanicus combats fatigue without amphetamine-mimetic activity. Phytotherapy Research 20:165-168.
• Ebadi, M., S. Sharma, P. Ghafourifar, H. Brown-Borg and H. El ReFaey. 2005. Peroxynitrite in the pathogenesis of Parkinson’s disease and the neuroprotective role of metallothioneins. Methods in Enzymology 396:276-298
• Brown-Borg, H.M., and S.G. Rakoczy. 2005. Glutathione metabolism in long-living Ames dwarf mice. Experimental Gerontology 40(1-2):115-120.
• Brown-Borg, H.M., S.G. Rakoczy and E.O. Uthus, 2005. Growth hormone alters methionine and glutathione metabolism in Ames dwarf mice. Mechanisms of Ageing & Development 126(3):389-398.
• Stauber, A.J., H.M. Brown-Borg, J. Liu, M.P. Waalkes, A. Laughter, R.A. Staben, J.C. Coley, C. Swanson, K.A. Voss, J.J. Kopchick and J.C. Corton. 2005. Constitutive expression of peroxisome proliferator-activated receptor a-regulated genes in dwarf mice. Molecular Pharmacology 67(3):681-694.
• Ebadi, M., H.M. Brown-Borg, H.El Refaey, B. Singh, S. Garrett, S. Shavali, and S.K. Sharma. 2005. Metallothionein-mediated neuroprotection in genetically engineered mouse models of Parkinson’s disease. Molecular Brain Research 134:67-75.
• Brown-Borg, H.M. 2005. Aging and Life Span. In: The Growth Hormone/Insulin-like Growth Factor Axis During Development. Advances in Experimental Medicine and Biology Eds. I.Varelo-Nieto, J.A. Chowen . Chapter 11. Springer, New York, NY. Volume 567 pp. 259-283
• Bartke, A. and H.M. Brown-Borg. 2004. Life extension in the dwarf mouse, In: Current Topics inDevelopmental Biology, Ed. G.P. Schatten. Chapter 6. Elsevier, Inc. 63:189-225.
• Brown-Borg, H.M. 2004. Antiaging supplement holds promise to halt age-related cognitive deterioration. Exp. Biol. Med. 229(5):367-368.
• Fan, L.-Q., H. Brown-Borg, S. Brown, R.J. Edwards, and J.C. Corton. 2004. Regulation of phase I and phase II steroid metabolism enzymes by PPARa activators. Toxicology 204(2-3):109-121.
• Fan, L.-Q., H. Brown-Borg, S. Brown, S. Westin, A. Mode, and J.C. Corton. 2004. PPARalpha activators down-regulate CYP2C7, a retinoic acid and testosterone hydroxylase. Toxicology 203(1-3):41-48.
• Brown-Borg, H.M., S.G. Rakoczy and E.O. Uthus. 2004. Growth hormone alters components of the glutathione metabolic pathway in Ames dwarf mice. Annals of the New York Academy of Sciences 1019:317-320.
• Romanick, M.A., S.G. Rakoczy and H.M. Brown-Borg. 2004. Long-lived Ames dwarf mouse exhibits increased antioxidant defense in skeletal muscle. Mech Ageing Dev. 125(4):269-281.
• Muralikrishnan, D., M. Ebadi and H.M. Brown-Borg. 2004. Effect of dopamine agonist 3-PPP hydrochloride against MPTP-induced neurotoxicity. Neurochemical Research. 29(2):379-384.
• Esquifino, A.I., A. Arce, M.P. Alvarez, V. Jimenez, H. Brown-Borg and A. Bartke. 2004. Light/dark h-prolactin effects on the ubmaxillary lymph nodes and spleen activity of Ames dwarf mice. Experimental Biology and Medicine (in press).
• Esquifino, A.I., A. Arce, M.P. Alvarez, F. Chacon, H. Brown-Borg and A. Bartke. 2004. Differential effects of light/dark recombinant h-prolactin administration on the submaxillary lymph nodes and spleen activity of adult male mice. Neuroimmunomodulation 11(2):119-126.
• Atwood, C.S., N. Barzilai, H.M. Brown-Borg, D.F. Jarrard, V.X. Fu, L.K. Heilbronn, D.K. Ingram, E. Ravussin, R.S.Schwartz and R. Weindruch. 2003. Pennington Scientific Symposium on Mechanisms and Retardation of Aging. Experimental Gerontology 38:1217-1226.
• Kennedy, M.A., S. G. Rakoczy and H.M. Brown-Borg. 2003. Long living Ames dwarf mouse hepatocytes readily undergo apoptosis. Experimental Gerontology 38:997-1008.
• Brown-Borg, H.M., and S. G. Rakoczy. 2003. Growth hormone administration to long-living dwarf mice alters multiple components of the antioxidative defense system. Mechanisms of Ageing and Development. 124:1013-1024.
• Brown-Borg, H.M. 2003. Hormonal regulation of aging and life span. Trends Endocrinol. Metab. 14(4):151-153.
• Uthus, E.O. and H.M. Brown-Borg. 2003. Altered methionine metabolism in long-living Ames dwarf mice. Experimental Gerontology 38:491-498.
• Ren, J., Z.K. Roughead, F.L. Norby, S. Rakoczy, L.E. Wold, R.L. Mabey, and H.M. Brown-Borg. 2003. Increases in insulin-like growth factor-1 level and peroxidative damage after gestational ethanol exposure in rats. Pharmacological Research 47(4):341-347.
• Brown-Borg, H.M. and S.M. Harman. 2003. Hormones and Oxidative Stress, In: Oxidative stress and aging: advances in basic science, diagnostics, and intervention, Eds. R.G. Cutler and H. Rodriguez. Chapter 61, World Scientific Publishing , River Edge, NJ, pp. 1070-1119.
• Esquifino, A.I., A. Arce, M.P. Alvarez, A. Szary, H. Brown-Borg and A. Bartke. 2002. Effects of overexpression of growth hormone on T cell activity in transgenic mice. J. Physiol. Biochem. 58(3):161-168.
• Ren, J. and H. M. Brown-Borg. 2002. Impaired cardiac excitation-contraction coupling in ventricular myocytes from Ames dwarf mice with IGF-I deficiency. Growth Hormone and IGF Research 12:99-105.
• Colligan, P.B., H.M. Brown-Borg, J. Duan, B.H. Ren, and J. Ren. 2002. Cardiac contractile function is enhanced in isolated ventricular myocytes from growth hormone transgenic mice. J. Endocrinology 173:257-264.
• Muralikrishnan, D., M. Ebadi, and H.M. Brown-Borg. 2002. Effect of MPTP on dopamine metabolism in Ames dwarf mice. Neurochemistry 27(6):457-464.
• Brown-Borg, H.M., S.G. Rakoczy, M.A. Romanick and M.A. Kennedy. 2002. Effects of growth hormone and insulin like growth factor-1 on hepatocyte antioxidative enzymes. Exp. Biol. Med. 227(2):94-104
• Brown-Borg, H.M., W.T. Johnson, S.G. Rakoczy, and M.A. Romanick. 2001. Mitochondrial oxidant production and oxidative damage in Ames dwarf mice. J. Am. Aging Assoc. 24(3):85-96.
• Bartke, A., H. Brown-Borg, J. Mattison, B. Kinney, S. Hauck, and C. Wright. 2001. Mini-Review: Prolonged longevity of hypopituitary dwarf mice. Experimental Gerontology 36(1): 21-28.
• Brown-Borg, H.M., and S.G. Rakoczy. 2000. Catalase expression in delayed and premature aging mouse models. Experimental Gerontology 35(2):199-212.
• Bartke, A., H.M. Brown-Borg, B. Kinney, J. Mattison, C. Wright, S. Hauck, K. Coschigano, and J. Kopchick. 2000. Growth hormone and aging. J. Am. Aging. Assoc. 23:219-225.
• Brown-Borg, H.M., A. M. Bode, and A. Bartke. 1999. Antioxidative mechanisms and plasma growth hormone levels: potential relationship in the aging process. Endocrine 11(1):41-48.
• Dialynas, E., H.M. Brown-Borg, and A. Bartke. 1999. Immune function in transgenic mice overexpressing growth hormone (GH) releasing hormone, GH or GH antagonist. Proc. Soc. Exp. Biol. Med. 221(3):178-183.
• Bartke, A., H.M. Brown-Borg, A.M. Bode, J. Carlson, W.S. Hunter and R.T. Bronson. 1998. Does growth hormone prevent or accelerate aging? Experimental Gerontology. 33:675-687.
• Brown-Borg, H.M., F. Blecha, and H.G. Klemcke. 1997. Influence of plasma prolactin concentrations and age on neonatal immune function. Comp. Biochem. Phys.118A(3):821- 829.
• Brown-Borg, H.M., K.E. Borg, C.J. Meliska and A. Bartke. 1996. Dwarf mice and the aging process. Nature 384:33.
• Brown-Borg, H.M., F.-P. Zhang, I. Huhtaniemi, and A. Bartke. 1996. Developmental onset of prolactin receptor gene expression in fetal and neonatal mice. Eur. J. Endo. 134(6):751-757.