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Training Grant-
Biology of Aging

Joseph Kemnitz

Joseph W. Kemnitz

Ph.D., University of Wisconsin-Madison
Professor, Dept. of Cell & Regenerative Biology
Interdepartmental Graduate Program in Nutritional Sciences; Conservation Biology & Sustainable Development Program, Gaylord Nelson Institute for Environmental Studies

Regulation of Energy Balance and the Processes of Aging

My laboratory studies the mechanisms that regulate food intake and energy expenditure and the consequences of caloric imbalances for health and risk of disease. Most of our projects utilize nonhuman primates, especially rhesus monkeys, because these animals share so many important characteristics with our own species.

Recent efforts have focused on changes that occur in middle and late life. Rhesus monkeys achieve adult body size by approximately eight years of age and can live as long as 40 years. Males are, on average, 25% heavier than females during adulthood. During middle age, monkeys of both sexes tend to add body fat and lose lean body mass, and some middle-aged monkeys develop marked obesity. Obese monkeys provide a good model for studying certain complications of human obesity. For example, there are similar abnormalities in glucose and lipid metabolism, blood pressure and hormone levels in the obese animals. Obese monkeys have elevated insulin levels and often impaired glucose tolerance. Their ability to maintain normal blood glucose levels declines as they get older, and some obese monkeys become diabetic in later life.

The effect of restricted food intake on aging is being assessed prospectively in a multidisciplinary study of rhesus monkeys. Half of the animals are being fed a moderately reduced amount of a nutritious diet, while the control monkeys are allowed to eat ad libitum. It is hypothesized that the food-restricted group will exhibit slower rates of change in certain characteristics of aging, including blood glucose regulation. Indeed, after ten years of study the restricted monkeys have greater insulin sensitivity, lower glucose concentrations and improved glucose tolerance. Their metabolism of energy is also affected. Beneficial effects of calorie restriction on brain structure and function are emerging. Such effects of reduced food intake in these restricted primates are consistent with the retardation of disease and extension of lifespan that has been demonstrated for food restricted non-primate species. If the phenomenon can be confirmed in primates, there would be a clearer potential for manipulating the course of aging by nutritional intervention in humans.

This work is conducted at the Wisconsin Primate Research Center, one of only eight such centers in the nation. The center is home to approximately 1500 monkeys. Research on the biology of aging is one of the major themes of our overall program, which involves nearly 250 investigators.

Representative Publications
Yamada, Y., Kemnitz, J.W., Weindruch, R., Anderson, R.M., Schoeller, D.A., & Colman, R.J. (2018). Caloric restriction and healthy life span: Frail phenotype of nonhuman primates in the Wisconsin national primate research center caloric restriction study. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 73(3), 273-278.
View publication via DOI: DOI:10.1093/gerona/glx059

Mattison, J. A., Colman, R. J., Beasley, T. M., Allison, D. B., Kemnitz, J. W., Roth, G. S., Ingram, D. K., Weindruch, R., de Cabo, R., & Anderson, R. M. (2017). Caloric restriction improves health and survival of rhesus monkeys. Nature Communications, 8, 14063.
View publication via DOI: DOI:10.1038/ncomms14063

Ziegler, T.E., Kapor, A., Hedman, C.J., Binkley, N., & Kemnitz, J.W. (2015). Measurement of 25-hydroxyvitamin D2&3 by tandem mass spectrometry: A primate multispecies comparison. American Journal of Primatology, 77(7), 801-810.
View publication via DOI: DOI:10.1002/ajp.22403

Fowler, C. G., Chiasson, K. B., Colman, R. J., Kemnitz, J. W., Beasley, T. M., & Weindruch, R. H. (2015). Hyperinsulinemia/diabetes, hearing, and aging in the University of Wisconsin calorie restriction monkeys. Hearing Research, 328, 78-86.
View publication via DOI: DOI:10.1016/j.heares.2015.07.001

Kolker, E., Ozdemir, V., Martens, L., . . . Kemnitz, J.W., . . . Yandl, G. (2014). Towards more transparent and reproducible omics studies through a common metadata checklist and data publications. OMICS, 18(1), 10-4.
View publication via DOI: DOI:10.1089/omi.2013.0149

Hedman, C.J., Wiebe, D.A., Dey, S., Plath, J., Kemnitz, J.W., & Ziegler, T.E. (2014). Development of a sensitive LC/MS/MS method for vitamin D metabolites: 1,25 dihydroxyvitamin D2&5 measurement using a novel derivatization agent. Journal of Chromatography B, 953, 62-67.
View publication via DOI: DOI:10.1016/j.jchromb.2014.01.045

Colman, R.J., Beasley, T.M., Kemnitz, J.W., Johnson, S.C., Weindruch, R., & Anderson, R.M. (2014). Caloric restriction increases age-related and all cause survival in rhesus monkeys. Nature Communications 5, 3557.
View publication via DOI: DOI:10.1038/ncomms4557

Sridharan, A., Bendlin, B. B., Gallagher, C. L., Oh, J. M., Willette, A. A., Alexander, A. L., Kemnitz, J. W., Colman, R. J., Weindruch, R. H., & Johnson, S. C. (2014). Effect of age and calorie restriction on corpus callosal integrity in rhesus macaques: A fiber tractography study. Neuroscience Letters, 569, 38-42.
View publication via DOI: DOI:10.1016/j.neulet.2014.03.047

Sridharan, A., Pehar, M., Salamat, M. S., Pugh, T. D., Bendlin, B. B., Willette, A. A., Anderson, R. M., Kemnitz, J. W., . . . Weindruch, R., Puglielli, L., & Johnson, S. C. (2013). Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: A preliminary quantitative imaging study. Brain Research, 1508, 1-8.
View publication via DOI: DOI:10.1016/j.brainres.2013.02.046

Yamada, Y., Colman, R. J., Kemnitz, J. W., Baum, S. T., Anderson, R. M., Weindruch, R., & Schoeller, D. A. (2013). Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in rhesus monkeys. Experimental Gerontology, 48(11), 1226-1235.
View publication via DOI: DOI:10.1016/j.exger.2013.08.002

Hall, K.D., Heymsfield, S.B., Kemnitz, J.W., Klein, S., Schoeller, D.A., & Speakman, J.R. (2012). Energy balance and its components: Implications for body weight regulation. American Journal of Clinical Nutrition, 95(4), 989-994.
View publication via DOI: DOI:10.3945/AJCN.112.036350

Willette, A.A., Bendlin, B.B., Colman, R.J., Kastman, E.K., Field, A.S., Alexander, A.L., ... Kemnitz, J.W., Weindruch, R.H., & Johnson, S. (2012). Calorie restriction reduces the influence of glucoregulator dysfunction on regional brain volume in aged rhesus monkeys. Diabetes, 61(5), 1036-1042.
View publication via DOI: DOI:10.2337/db11-1187

Sridharan, A., Willette, A. A., Bendlin, B. B., Alexander, A. L., Coe, C. L., Voytko, M. L., Coleman, R. J., Kemnitz, J. W., Weindruch, R. H., & Johnson, S. C. (2012). Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys. Front Aging Neurosci, 4, 31.
View publication via DOI: DOI:10.3389/fnagi.2012.00031

Hofer-Inteeworn, N., Panciera, D. L., Monroe, W. E., Saker, K. E., Davies, R. H., Refsal, K. R., & Kemnitz, J. W. (2012). Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs. American Journal of Veterinary Research, 73(4), 529-538.
View publication via DOI: DOI:10.2460/ajvr.73.4.529

Kemnitz, J.W. (2011). Calorie restriction and aging in nonhuman primates. Institute of Laboratory Animal Resources Journal, 52(1), 66-77.

Klimentidid, Y.C., Beasley, T.M., Lin, H-Y., Murati, G., Glass, G.E., Guyton, M., ... Kemnitz, J., ... Allison, D.A. (2011). Canaries in the coal mine: A cross-species analysis of the plurality of obesity epidemics. Proceedings of the Royal Society B (Biological Sciences), 278(1712), 1626-1632.
View publication via DOI: DOI:10.1098/rspb.2010.1890

Swanson, C.R, Joers, V., Bondarenko, V., Brunner, K., Simmons, H.A., Ziegler, T. E., Kemnitz, J.W., Johnson, J.A., & Emborg, M.E. (2011). The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys. Journal of Neuroinflammation, 8, 91-105.
View publication via DOI: DOI:10.1186/1742-2094-8-91

Fowler, C.G., Chiasson, K.B., Leslie, T.H., Thomas, D., Beasley, T.M., Kemnitz, J.W., & Weindruch, R. (2010). Auditory function in rhesus monkeys: Effects of aging and caloric restriction in the Wisconsin monkeys five years later. Hearing Research, 261(1-2), 75-81.
Click here to download this publication.
View publication via DOI: DOI:10.1016/j.heares.2010.01.006

Colman, R.J., Anderson, R.M., Johnson, S.C., Kastman, E.K., Kosmatka, K.J., T. Beasley, T.M., Allison, D.B., Cruzen, C., Simmons, H.A., Kemnitz, J.W., & Weindruch, R. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325, 201-204.
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View publication via DOI: DOI:10.1126/science.1173635

Lin, J., Kennedy, S.H., Svarovsky, T., Rogers, J., Kemnitz, J.W., Xu, A., Zondervan, K.T. (2009). High-quality genomic DNA extraction from formalin-fixed and paraffin-embedded samples deparaffinized using mineral oil. Analytical Biochemistry, 395(2), 265-267.
View publication via DOI: DOI:10.1016/j.ab.2009.08.016

Fowler, C.G., Chiasson, K.B., Hart, D.B., Beasley, T.M., Kemnitz, J., & Weindruch, R. (2008). Tympanometry in rhesus monkeys: Effects of aging and caloric restriction. Int. J. Audiol., 47(4), 209-14.
View publication via DOI: DOI:10.1080/14992020701851882

Raman, A., Ramsey, J.J., Kemnitz, J.W., Baum, S.T., Newton, W., Coleman, R.J., Weindruch, R., Beasley, M.T., & Schoeller, D.A. (2007). Influences of calorie restriction and age on energy expenditure in the rhesus monkeys. Am. J. Physiol., 292, E101-6.
View publication via DOI: DOI:10.​1152/​ajpendo.​00127.​2006

Raman, A., Baum, S.T., Colman, R.J., Kemnitz, J.W., Weindruch, R., & Schoeller, D.A. (2007). Metabolizable energy intake during long-term calorie restriction in rhesus monkeys. Exp. Gerontol., 42(10), 988-94.
View publication via DOI: DOI:10.1016/j.exger.2007.05.008

Zhou, R., Bruns, C.M., Bird, I.M., Kemnitz, J.W., Goodfriend, T.L., Dumesic, D.A., & Abbott, D.H. (2007). Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of prenatally androgenized female rhesus monkeys. Reprod. Toxicol., 23(3), 438-48.
View publication via DOI: DOI:10.1016/j.reprotox.2006.12.009

Raman, A., Colman, R.J., Cheng, Y., Kemnitz, J.W., Baum, S.T., Weindruch, R., & Schoeller, D.A. (2005). Reference body composition in adult rhesus monkeys: Glucoregulatory and anthropometric indices. J. Gerontol. A. Biol. Sci. Med. Sci., 60(12), 1518-24.
View publication via DOI: DOI:10.1093/gerona/60.12.1518

Blanc, S., Colman, R., Kemnitz, J., Weindruch, R., Baum, S., Ramsey, J., & Schoeller, D. (2005). Assessment of nutritional status in rhesus monkeys: comparison of dual-energy X-ray absorptiometry and stable isotope dilution. J. Med. Primatol., 34(3), 130-8.
View publication via DOI: DOI:10.1111/j.1600-0684.2005.00106.x

Ramsey, J.J., Kemnitz, J.W., Newton, W., Hagopian, K., Patterson, T.A., & Swick, A.G. (2005). Food intake in rhesus monkeys following central administration of orexins. Regul. Pept., 124(1-3), 209-14.
View publication via DOI: DOI:10.1016/j.regpep.2004.07.018

Bruns, C.M., Baum, S.T., Colman, R.J., Eisner, J.R., Kemnitz, J.W., Weindruch, R., & Abbott, D.H. (2004). Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys. J. Clin. Endocrinol. Metab., 89(12), 6218-23.
View publication via DOI: DOI:10.1210/jc.2004-0918

Bruns, C.M., & Kemnitz, J.W. (2004). Sex hormones, insulin sensitivity, and diabetes mellitus. ILAR J., 45(2), 160-9.

Zondervan, K.T., Weeks, D.E., Colman, R.C., Cardon, L.R., Hadfield, R., Scheffler, J., Goudy, T.A, Coe, C.L., Kemnitz, J.W., & Kennedy, S.H. (2004). Familial aggregation of endometriosis in a large pedigree of rhesus macaques. Human Reproduction, 19, 448-455.
View publication via DOI: DOI:10.1093/humrep/deh052

Blanc, S., Schoeller, D., Kemnitz, J., Weindruch, R., Colman, R., Newton, W., Wink, K., Baum, S., & Ramsey, J. (2003). Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction. J. Clin. Endocrinol. Metab., 88, 16-23.
View publication via DOI: DOI:10.1210/jc.2002-020405

Fowler, C.G., Torre, P., & Kemnitz, J.W. (2002). Effects of dietary restriction and aging on the auditory function of rhesus monkeys (Macaca mulatta): The University of Wisconsin Study. Hearing Research, 169, 24-35.

Gresl, T.A., Colman, R.J., Roecker, E.B., Havighurst, T.C., Huang, Z., Allison, D.B., Bergman R.N., & Kemnitz, J.W. (2002). Dietary restriction and glucose regulation in aging rhesus monkeys: A follow-up report at 8.5 years. American Journal of Physiology: Endocrinology and Metabolism, 281, E757-765.

Ramsey, J.J., Laatsch, J.L., & Kemnitz, J.W. (2000). Age and gender differences in body composition, energy expenditure, and glucoregulation of adult rhesus monkeys. Journal of Medical Primatology, 29(1), 11-19.
View publication via DOI: DOI:10.1034/j.1600-0684.2000.290102.x

Kemnitz, J.W., Roecker, E.B., Haffa, A.L., Pinheiro, J., Kurzman I., Ramsey, J.J., & MacEwen, E.G. (2000). Serum dehydroepiandrosterone sulfate concentrations across the life span of laboratory-housed rhesus monkeys. J. Med. Primatol., 29(5), 330-337.
View publication via DOI: DOI:10.1034/j.1600-0684.2000.290504.x

Ramsey, J.J., Colman, R.J., Binkley, N.C., Christensen, J.D., Gresl, T.A., Kemnitz, J.W., & Weindruch, R. (2000). Dietary restriction and aging in rhesus monkeys: The University of Wisconsin Study. Exp. Gerontol., 35, 1131-1149.

Schroederus, K.M, Gresl, T.A, & Kemnitz, J.W. (1999). Reduced water intake but normal response to acute water deprivation in elderly rhesus monkeys. Aging: Clinical and Experimental Research, 11, 101-108.

Colman, R., & Kemnitz, J.W. (1998). Aging experiments using nonhuman primates. In B.P. Yu (Ed.), Methods in aging research. Boca Raton: CRC.

Colman, R.J., Roecker, E.B., Ramsey, J.J.,& Kemnitz, J.W. (1998). The effect of dietary restriction on body composition in adult male and female rhesus macaques. Aging: Clinical and Experimental Research, 10, 83-92.

Kemnitz, J.W., Holston, K.A., & Colman, R.J. (1998). Nutrition, aging and reproduction in rhesus monkeys. In W. Hansel, G.A. Bray, & D.H. Ryan (Eds.), Pennington Center Nutrition Series. Part IV. Evolution of research methods in nutrition and reproduction. Baton Rouge: Louisiana State University Press.

Uno, H., Alsum, P., Zimbric, S.M.L., Houser, W.D., Thomson, J.A., & Kemnitz, J.W. (1998). Colon cancer in aged captive rhesus monkeys (Macaca mulatta). American Journal of Primatology, 44, 19-27.
View publication via DOI: DOI:10.1002/(SICI)1098-2345(1998)44:1<19::AID-AJP2>3.0.CO;2-#

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