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.

2019

Ahn B, Ranjit R, Premkumar P, Pharaoh G, Piekarz KM, Matsuzaki S, Claflin DR, Riddle K, Judge J, Bhaskaran S, Satara Natarajan K, Barboza E, Wronowski B, Kinter M, Humphries KM, Griffin TM, Freeman WM, Richardson A, Brooks SV, Van Remmen H. Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fibre branching. J Cachexia Sarcopenia Muscle 10:411-428, 2019 April, PMID: 30706998, PMCID: PMC6463475

Ahn B, Smith N, Saunders D, Ranjit R, Kneis P, Towner RA, Van Remmen H. Using MRI to measure in vivo free radical production and perfusion dynamics in a mouse model of elevated oxidative stress and neurogenic atrophy. Redox Biol 26:101308, 2019 August, PMID: 31470261, PMCID: PMC6831885

Batushansky A, Lopes EBP, Zhu S, Humphries KM, Griffin TM. GC-MS Method for Metabolic Profiling of Mouse Femoral Head Articular Cartilage Reveals Distinct Effects of Tissue Culture and Development. Osteoarthritis Cartilage, 2019 May, PMID: 31136803, PMCID: PMC6702098

Batushansky A, Matsuzaki S, Newhardt MF, West MS, Griffin TM, Humphries KM. GC-MS metabolic profiling reveals fructose-2,6-bisphosphate regulates branched chain amino acid metabolism in the heart during fasting. Metabolomics 15:18, 2019 January, PMID: 30830475, PMCID: PMC6478396

Borcherding DC, Siefert ME, Lin S, Brewington J, Sadek H, Clancy JP, Plafker SM, Ziady AG.. Clinically-approved CFTR modulators rescue Nrf2 dysfunction in cystic fibrosis airway epithelia. J Clin Invest 130, 2019 May, PMID: 31145101, PMCID: PMC6668689

Coen PM, Musci RV, Hinkley JM, Miller BF. Mitochondria as a Target for Mitigating Sarcopenia. Front Physiol 9:1883, 2019 January, PMID: 30687111, PMCID: PMC6335344

Deepa SS, Van Remmen H, Brooks SV, Faulkner JA, Larkin L, McArdle A, Jackson MJ, Vasilaki A, Richardson A. Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice. Free Radic Biol Med 132:19-23, 2019 February, PMID: 30670156, PMCID: PMC6405207

Delacruz RGC, Sandoval IT, Chang K, Miller BN, Reyes-Uribe L, Borras E, Lynch PM, Taggart MW, Hawk ET, Vilar E, Jones DA. Functional characterization of CNOT3 variants identified in familial adenomatous polyposis adenomas. Oncotarget 10:3939-3951, 2019 June, PMID: 31231471, PMCID: PMC6570471

Dominguez-Lopez S, Sharma R, Beckstead MJ. Neurotensin receptor 1 deletion decreases methamphetamine self-administration and the associated reduction in dopamine cell firing. Addict Biol:e12854, 2019 November, PMID: 31742874

Griffin TM, Scanzello CR. Innate inflammation and synovial macrophages in osteoarthritis pathophysiology. Clin Exp Rheumatol 37 Suppl 120:57-63, 2019 September, PMID: 31621560, PMCID: PMC6842324

Groennebaek T, Sieljacks P, Nielsen R, Pryds K, Jespersen NR, Wang J, Carlsen CR, Schmidt MR, de Paoli FV, Miller BF, Vissing K, Bøtker HE. Effect of Blood Flow Restricted Resistance Exercise and Remote Ischemic Conditioning on Functional Capacity and Myocellular Adaptations in Patients With Heart Failure. Circ Heart Fail 12:e006427, 2019 December, PMID: 31830830

Konopka AR, Laurin JL, Schoenberg HM, Reid JJ, Castor WM, Wolff CA, Musci RV, Safairad OD, Linden MA, Biela LM, Bailey SM, Hamilton KL, Miller BF. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell 18:e12880, 2019 February, PMID: 30548390, PMCID: PMC6351883

Konopka AR, Miller BF. Taming expectations of metformin as a treatment to extend healthspan. Geroscience, 2019 February, PMID: 30746605, PMCID: PMC6544683

Miller BF, Baehr LM, Musci RV, Reid JJ, Peelor FF 3rd, Hamilton KL, Bodine SC. Muscle-specific changes in protein synthesis with aging and reloading after disuse atrophy. J Cachexia Sarcopenia Muscle, 2019 July, PMID: 31313502, PMCID: PMC6903438

Miller BF, Pharaoh GA, Hamilton KL, Peelor FF, Kirkland JL, Freeman WM, Mann SN, Kinter M, Price JC, Stout MB. Short-term calorie restriction and 17α-estradiol administration elicit divergent effects on proteostatic processes and protein content in metabolically active tissues. J Gerontol A Biol Sci Med Sci, 2019 May, PMID: 31074767

Newhardt MF, Batushansky A, Matsuzaki S, Young ZT, West M, Chin NC, Szweda LI, Kinter M, Humphries KM. Enhancing cardiac glycolysis causes an increase in PDK4 content in response to short term high fat diet. J Biol Chem, 2019 September, PMID: 31562244, PMCID: PMC6851294

Newman AH, Cao J, Keighron JD, Jordan CJ, Bi GH, Liang Y, Abramyan AM, Avelar AJ, Tschumi CW, Beckstead MJ, Shi L, Tanda G, Xi ZX. Translating the atypical dopamine uptake inhibitor hypothesis toward therapeutics for treatment of psychostimulant use disorders. Neuropsychopharmacology, 2019 March, PMID: 30858517, PMCID: PMC6785152

Pearsall EA, Cheng R, Matsuzaki S, Zhou K, Ding L, Ahn B, Kinter M, Humphries KM, Quiambao AB, Farjo RA, Ma JX. Neuroprotective effects of PPARα in retinopathy of type 1 diabetes. PLoS One 14:e0208399, 2019 February, PMID: 30716067, PMCID: PMC6361421

Pharaoh G, Owen D, Yeganeh A, Premkumar P, Farley J, Bhaskaran S, Ashpole N, Kinter M, Van Remmen H, Logan S. Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function. Mol Neurobiol, 2019 November, PMID: 31732912

Pharaoh G, Sataranatarajan K, Street K, Hill S, Gregston J, Ahn B, Kinter C, Kinter M, Van Remmen H. Metabolic and Stress Response Changes Precede Disease Onset in the Spinal Cord of Mutant SOD1 ALS Mice. Front Neurosci 13:487, 2019 May, PMID: 31213966, PMCID: PMC6554287

Piccart E, Tschumi CW, Beckstead MJ. Acute and subchronic PCP attenuate D2 autoreceptor signaling in substantia nigra dopamine neurons. Eur Neuropsychopharmacol 29:444-449, 2019 March, PMID: 30686631, PMCID: PMC6421099

Qaisar R, Bhaskaran S, Ranjit R, Sataranatarajan K, Premkumar P, Huseman K, Van Remmen H. Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and weakness. Redox Biol 20:68-74, 2019 January, PMID: 30296699, PMCID: PMC6174848

Rangaraju V, Lewis TL Jr, Hirabayashi Y, Bergami M, Motori E, Cartoni R, Kwon SK, Courchet J. Pleiotropic Mitochondria: The Influence of Mitochondria on Neuronal Development and Disease. J Neurosci 39:8200-8208, 2019 October, PMID: 31619488, PMCID: PMC6794931

Reid JJ, Linden MA, Peelor FF, Miller RA, Hamilton KL, Miller BF. Brain Protein Synthesis Rates in the UM-HET3 Mouse Following Treatment with Rapamycin or Rapamycin with Metformin. J Gerontol A Biol Sci Med Sci, 2019 March, PMID: 30864661

Sieljacks P, Wang J, Groennebaek T, Rindom E, Jakobsgaard JE, Herskind J, Gravholt A, Møller AB, Musci RV, de Paoli FV, Hamilton KL, Miller BF, Vissing K. Six Weeks of Low-Load Blood Flow Restricted and High-Load Resistance Exercise Training Produce Similar Increases in Cumulative Myofibrillar Protein Synthesis and Ribosomal Biogenesis in Healthy Males. Front Physiol 10:649, 2019 May, PMID: 31191347, PMCID: PMC6548815

Sivasami P, Poudel N, Munteanu MC, Hudson J, Lovern P, Liu L, Griffin T, Hinsdale ME. Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice. Int J Obes (Lond), 2019 February, PMID: 30778123

Tarantini S, Valcarcel-Ares MN, Toth P, Yabluchanskiy A, Tucsek Z, Kiss T, Hertelendy P, Kinter M, Ballabh P, Süle Z, Farkas E, Baur JA, Sinclair DA, Csiszar A, Ungvari Z. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol 24:101192, 2019 April, PMID: 31015147, PMCID: PMC6477631

Tschumi CW, Beckstead MJ. Diverse actions of the modulatory peptide neurotensin on central synaptic transmission. Eur J Neurosci 49:784-793, 2019 March, PMID: 29405480, PMCID: PMC6078827

Tschumi CW, Daszkowski AW, Sharpe AL, Trzeciak M, Beckstead MJ. A history of ethanol drinking increases locomotor stimulation and blunts enhancement of dendritic dopamine transmission by methamphetamine. Addict Biol:e12763, 2019 May, PMID: 31062485, PMCID: PMC6832768

Wolff CA, Reid JJ, Musci RV, Linden MA, Konopka AR, Peelor FF, Miller BF, Hamilton KL. 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, 2019 March, PMID: 30820523, PMCID: PMC6909916

Yang X, Brobst D, Chan WS, Tse MCL, Herlea-Pana O, Ahuja P, Bi X, Zaw AM, Kwong ZSW, Jia WH, Zhang ZG, Zhang N, Chow SKH, Cheung WH, Louie JCY, Griffin TM, Nong W, Hui JHL, Du GH, Noh HL, Saengnipanthkul S, Chow BKC, Kim JK, Lee CW, Chan CB. Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility. Sci Signal 12, 2019 August, PMID: 31409756

Zhu S, Makosa D, Miller B, Griffin TM. Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis. Connect Tissue Res:1-14, 2019 September, PMID: 31522568, PMCID: PMC6884680

Zyla K, Larabee CM, Georgescu C, Berkley C, Reyna T, Plafker SM. Dimethyl fumarate mitigates optic neuritis. Mol Vis 25:446-461, 2019 August, PMID: 31523122, PMCID: PMC6707756

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