Aging & Metabolism Research Program

Metabolism produces the building blocks and energy necessary for life through an elegant series of dynamically regulated biochemical transformations. Defects in metabolism arise as we age. Scientists in the Aging and Metabolism Research Program have a common interest in the metabolic basis of age-related disease and in extending the health of our aging population.

Our investigators study a variety of age-related diseases integrated across multiple organ systems, including heart failure, diabetic cardiomyopathy, macular degeneration, osteoarthritis, sarcopenia, and neurodegenerative disorders. Common among these afflictions are alterations in cellular metabolism and energy production. Mitochondria are intracellular organelles that play an essential role in metabolism and in the response of cells to physiologic and pathophysiologic stress. The laboratories that comprise our Program investigate distinct aspects of mitochondrial and cellular metabolism, identifying alterations that occur with age that are exacerbated by obesity and diabetes. Associated defects in energy homeostasis, cellular and mitochondrial quality control, production and removal of toxic free radical species, and the inflammatory response are explored to define underlying causes of diseases that primarily afflict the elderly. Together, these multidisciplinary approaches create a synergistic, collaborative, and creative environment that fosters discovery and training.

2020

Qaisar R, Pharaoh G, Bhaskaran S, Xu H, Ranjit R, Bian J, Ahn B, Georgescu C, Wren JD, Van Remmen H. Restoration of Sarcoplasmic Reticulum Ca2 ATPase (SERCA) Activity Prevents Age-Related Muscle Atrophy and Weakness in Mice. Int J Mol Sci 22, 2020 December, PMID: 33375170, PMCID: PMC7792969

Figueiredo VC, D'Souza RF, Van Pelt DW, Lawrence MM, Zeng N, Markworth JF, Poppitt SD, Miller BF, Mitchell CJ, McCarthy JJ, Dupont-Versteegden EE, Cameron-Smith D. Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading. J Cachexia Sarcopenia Muscle, 2020 November, PMID: 33231914

Chucair-Elliott AJ, Ocañas SR, Stanford DR, Ansere VA, Buettner KB, Porter H, Eliason NL, Reid JJ, Sharpe AL, Stout MB, Beckstead MJ, Miller BF, Richardson A, Freeman WM. Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia. Commun Biol 3:693, 2020 November, PMID: 33214681, PMCID: PMC7678837

Elayapillai S, Ramraj S, Benbrook DM, Bieniasz M, Wang L, Pathuri G, Isingizwe ZR, Kennedy AL, Zhao YD, Lightfoot S, Hunsucker LA, Gunderson CC. Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer. Gynecol Oncol, 2020 October, PMID: 33131904

Bergstrom K, Shan X, Casero D, Batushansky A, Lagishetty V, Jacobs JP, Hoover C, Kondo Y, Shao B, Gao L, Zandberg W, Noyovitz B, McDaniel JM, Gibson DL, Pakpour S, Kazemian N, McGee S, Houchen CW, Rao CV, Griffin TM, Sonnenburg JL, McEver RP, Braun J, Xia L. Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota. Science 370:467-472, 2020 October, PMID: 33093110

Brown JL, Lawrence MM, Ahn B, Kneis P, Piekarz KM, Qaisar R, Ranjit R, Bian J, Pharaoh G, Brown C, Peelor FF 3rd, Kinter MT, Miller BF, Richardson A, Van Remmen H. Cancer cachexia in a mouse model of oxidative stress. J Cachexia Sarcopenia Muscle, 2020 September, PMID: 32918528, PMCID: PMC7749559

Bhaskaran S, Pollock N, C Macpherson P, Ahn B, Piekarz KM, Staunton CA, Brown JL, Qaisar R, Vasilaki A, Richardson A, McArdle A, Jackson MJ, Brooks SV, Van Remmen H. Neuron-specific deletion of CuZnSOD leads to an advanced sarcopenic phenotype in older mice. Aging Cell:e13225, 2020 September, PMID: 32886862, PMCID: PMC7576239

Miller BF, Thyfault JP. Exercise-Pharmacology Interactions: Metformin, Statins, and Healthspan. Physiology (Bethesda) 35:338-347, 2020 September, PMID: 32783612, PMCID: PMC7642846

Eyster CA, Matsuzaki S, Newhardt MF, Giorgione JR, Humphries KM. Diabetes induced decreases in PKA signaling in cardiomyocytes: The role of insulin. PLoS One 15:e0231806, 2020 August, PMID: 32817622, PMCID: PMC7444578

Pharaoh G, Brown JL, Sataranatarajan K, Kneis P, Bian J, Ranjit R, Hadad N, Georgescu C, Rabinovitch P, Ran Q, Wren JD, Freeman W, Kinter M, Richardson A, Van Remmen H. Targeting cPLA2 derived lipid hydroperoxides as a potential intervention for sarcopenia. Sci Rep 10:13968, 2020 August, PMID: 32811851, PMCID: PMC7435184

Wolff CA, Lawrence MM, Porter H, Zhang Q, Reid JJ, Laurin JL, Musci RV, Linden MA, Peelor FF 3rd, Wren JD, Creery JS, Cutler KJ, Carson RH, Price JC, Hamilton KL, Miller BF. Sex differences in changes of protein synthesis with rapamycin treatment are minimized when metformin is added to rapamycin. Geroscience, 2020 August, PMID: 32761290

Howell RD, Dominguez-Lopez S, Ocañas SR, Freeman WM, Beckstead MJ. Female mice are resilient to age-related decline of substantia nigra dopamine neuron firing parameters. Neurobiol Aging 95:195-204, 2020 August, PMID: 32846275, PMCID: PMC7606778

Hossen MN, Wang L, Chinthalapally HR, Robertson JD, Fung KM, Wilhelm S, Bieniasz M, Bhattacharya R, Mukherjee P. Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome. Sci Adv 6:eaba5379, 2020 July, PMID: 32743073, PMCID: PMC7375829

Chiao YA, Zhang H, Sweetwyne M, Whitson J, Ting YS, Basisty N, Pino LK, Quarles E, Nguyen NH, Campbell MD, Zhang T, Gaffrey MJ, Merrihew G, Wang L, Yue Y, Duan D, Granzier HL, Szeto HH, Qian WJ, Marcinek D, MacCoss MJ, Rabinovitch P. Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. Elife 9, 2020 July, PMID: 32648542, PMCID: PMC7377906

Van Pelt DW, Vechetti IJ Jr, Lawrence MM, Van Pelt KL, Patel P, Miller BF, Butterfield TA, Dupont-Versteegden EE. Serum extracellular vesicle miR-203a-3p content is associated with skeletal muscle mass and protein turnover during disuse atrophy and regrowth. Am J Physiol Cell Physiol, 2020 July, PMID: 32639875, PMCID: PMC7500218

Lawrence MM, Van Pelt DW, Confides AL, Hettinger ZR, Hunt ER, Reid JJ, Laurin JL, Peelor FF 3rd, Butterfield TA, Miller BF, Dupont-Versteegden EE. Muscle from aged rats is resistant to mechanotherapy during atrophy and reloading. Geroscience, 2020 June, PMID: 32588343

Olson AL, Humphries K. Recent advances in understanding glucose transport and glucose disposal. F1000Res 9, 2020 June, PMID: 32595948, PMCID: PMC7315251

Zhao M, Kao CS, Arndt C, Tran DD, Cho WI, Maksimovic K, Chen XXL, Khan M, Zhu H, Qiao J, Peng K, Hong J, Xu J, Kim D, Kim JR, Lee J, van Bruggen R, Yoon WH, Park J. Knockdown of genes involved in axonal transport enhances the toxicity of human neuromuscular disease-linked MATR3 mutations in Drosophila. FEBS Lett, 2020 June, PMID: 32515490

Sataranatarajan K, Pharaoh G, Brown JL, Ranjit R, Piekarz KM, Street K, Wren JD, Georgescu C, Kinter C, Kinter M, Freeman WM, Richardson A, Van Remmen H. Molecular changes in transcription and metabolic pathways underlying muscle atrophy in the CuZnSOD null mouse model of sarcopenia. Geroscience, 2020 May, PMID: 32394347, PMCID: PMC7394980

Yap ZY, Strucinska K, Matsuzaki S, Lee S, Si Y, Humphries K, Tarnopolsky MA, Yoon WH. A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease. J Inherit Metab Dis, 2020 May, PMID: 32383294, PMCID: PMC7647956

Wolff CA, Reid JJ, Musci RV, Bruns DR, Linden MA, Konopka AR, Peelor FF, Miller BF, Hamilton KL. Corrigendum to: Differential Effects of Rapamycin and Metformin in Combination With Rapamycin on Mechanisms of Proteostasis in Cultured Skeletal Myotubes. J Gerontol A Biol Sci Med Sci 75:892, 2020 April, PMID: 32302402, PMCID: PMC7164524

Griffin TM, Lories RJ. Cracking the code on the innate immune program in OA. Osteoarthritis Cartilage, 2020 April, PMID: 32278072

Groennebaek T, Nielsen J, Jespersen NR, Botker HE, de Paoli FV, Miller BF, Vissing K. Utilization of biomarkers as predictors of skeletal muscle mitochondrial content after physiological intervention and in clinical settings. Am J Physiol Endocrinol Metab, 2020 April, PMID: 32255679

Miller BF, Reid JJ, Price JC, Lin HL, Atherton PJ, Smith K. CORES OF REPRODUCIBILITY IN PHYSIOLOGY: THE USE OF DEUTERATED WATER FOR THE MEASUREMENT OF PROTEIN SYNTHESIS. J Appl Physiol (1985), 2020 March, PMID: 32213116

Sun C, Sakashita H, Kim J, Tang Z, Upchurch GM, Yao L, Berry WL, Griffin TM, Olson LE. Mosaic Mutant Analysis Identifies PDGFRα/PDGFRβ as Negative Regulators of Adipogenesis. Cell Stem Cell, 2020 March, PMID: 32229310, PMCID: PMC7214206

Piekarz KM, Bhaskaran S, Sataranatarajan K, Street K, Premkumar P, Saunders D, Zalles M, Gulej R, Khademi S, Laurin J, Peelor R, Miller BF, Towner R, Van Remmen H. Molecular changes associated with spinal cord aging. Geroscience, 2020 March, PMID: 32144690, PMCID: PMC7205981

Lawrence MM, Van Pelt DW, Confides AL, Hunt ER, Hettinger ZR, Laurin JL, Reid JJ, Peelor FF 3rd, Butterfield TA, Dupont-Versteegden EE, Miller BF. Massage as a mechanotherapy promotes skeletal muscle protein and ribosomal turnover but does not mitigate muscle atrophy during disuse in adult rats. Acta Physiol (Oxf):e13460, 2020 March, PMID: 32125770, PMCID: PMC7293583

Griffin TM, Batushansky A, Hudson J, Lopes EBP. Correlation network analysis shows divergent effects of a long-term, high-fat diet and exercise on early stage osteoarthritis phenotypes in mice. J Sport Health Sci 9:119-131, 2020 March, PMID: 32099720, PMCID: PMC7031811

Ehrlicher SE, Stierwalt HD, Miller BF, Newsom SA, Robinson MM. Mitochondrial adaptations to exercise do not require Bcl2-mediated autophagy but occur with BNIP3/Parkin activation. FASEB J, 2020 February, PMID: 32030805

Quarles E, Basisty N, Chiao YA, Merrihew G, Gu H, Sweetwyne MT, Fredrickson J, Nguyen NH, Razumova M, Kooiker K, Moussavi-Harami F, Regnier M, Quarles C, MacCoss M, Rabinovitch PS. Rapamycin persistently improves cardiac function in aged, male and female mice, even following cessation of treatment. Aging Cell 19:e13086, 2020 February, PMID: 31823466, PMCID: PMC6996961

Cardoso AC, Lam NT, Savla JJ, Nakada Y, Pereira AHM, Elnwasany A, Menendez-Montes I, Ensley EL, Petric UB, Sharma G, Sherry AD, Malloy CR, Khemtong C, Kinter MT, Tan WLW, Anene-Nzelu CG, Foo RS, Nguyen NUN, Li S, Ahmed MS, Elhelaly WM, Abdisalaam S, Asaithamby A, Xing C, Kanchwala M, Vale G, Eckert KM, Mitsche MA, McDonald JG, Hill JA, Huang L, Shaul PW, Szweda LI, Sadek HA. Mitochondrial Substrate Utilization Regulates Cardiomyocyte Cell Cycle Progression. Nat Metab 2:167-178, 2020 February, PMID: 32617517, PMCID: PMC7331943

Gunning AC, Strucinska K, Muñoz Oreja M, Parrish A, Caswell R, Stals KL, Durigon R, Durlacher-Betzer K, Cunningham MH, Grochowski CM, Baptista J, Tysoe C, Baple E, Lahiri N, Homfray T, Scurr I, Armstrong C, Dean J, Fernandez Pelayo U, Jones AWE, Taylor RW, Misra VK, Yoon WH, Wright CF, Lupski JR, Spinazzola A, Harel T, Holt IJ, Ellard S. Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism. Am J Hum Genet, 2020 January, PMID: 32004445, PMCID: PMC7010973

Griffin TM, Friedman JE. How can parental obesity promote OA across generations? Nat Rev Rheumatol, 2020 January, PMID: 31949286

Aging and Metabolism Research Program
Oklahoma Medical Research Foundation
825 NE 13th Street, MS 21
Oklahoma City, OK 73104

Phone: (405) 271-7570
Fax: (405) 271-1437
Email: Jeannie-Evans@omrf.org