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

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

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

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

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

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

2018

Ahn B, Pharaoh G, Premkumar P, Huseman K, Ranjit R, Kinter M, Szweda L, Kiss T, Fulop G, Tarantini S, Csiszar A, Ungvari Z, Van Remmen H. Nrf2 deficiency exacerbates age-related contractile dysfunction and loss of skeletal muscle mass. Redox Biol 17:47-58, 2018 July, PMID: 29673700, PMCID: PMC6006677

Bhaskaran S, Pharaoh G, Ranjit R, Murphy A, Matsuzaki S, Nair BC, Forbes B, Gispert S, Auburger G, Humphries KM, Kinter M, Griffin TM, Deepa SS. Loss of mitochondrial protease ClpP protects mice from diet-induced obesity and insulin resistance. EMBO Rep 19, 2018 March, PMID: 29420235, PMCID: PMC5836096

Brown JL, Lee DE, Rosa-Caldwell ME, Brown LA, Perry RA, Haynie WS, Huseman K, Sataranatarajan K, Van Remmen H, Washington TA, Wiggs MP, Greene NP. Protein imbalance in the development of skeletal muscle wasting in tumour-bearing mice. J Cachexia Sarcopenia Muscle 9:987-1002, 2018 October, PMID: 30328290, PMCID: PMC6204589

Chen C1, Zhong Y, Wang JJ, Yu Q, Plafker K, Plafker S, Zhang SX. Regulation of Nrf2 by X Box-Binding Protein 1 in Retinal Pigment Epithelium. Front Genet 9:658, 2018 December, PMID: 30619478, PMCID: PMC6306429

Deepa SS, Pharaoh G, Kinter M, Diaz V, Fok WC, Riddle K, Pulliam D, Hill S, Fischer KE, Soto V, Georgescu C, Wren JD, Viscomi C, Richardson A, Van Remmen H. Lifelong reduction in complex IV induces tissue-specific metabolic effects but does not reduce lifespan or healthspan in mice. Aging Cell:e12769, 2018 April, PMID: 29696791, PMCID: PMC6052393

Dominguez-Lopez S, Piccart E, Lynch WB, Wollet MB, Sharpe AL, Beckstead MJ. Antagonism of Neurotensin Receptors in the Ventral Tegmental Area Decreases Methamphetamine Self-Administration and Methamphetamine Seeking in Mice. Int J Neuropsychopharmacol 21:361-370, 2018 April, PMID: 29272412, PMCID: PMC5888879

Donovan EL, Lopes EBP, Batushansky A, Kinter M, Griffin TM. Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice. Dis Model Mech 11, 2018 August, PMID: 30018076, PMCID: PMC6176996

Flores LC, Roman MG, Cunningham GM, Cheng C, Dube S, Allen C, Van Remmen H, Hubbard GB, Saunders TL, Ikeno Y. Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice. Pathobiol Aging Age Relat Dis 8:1533754, 2018 October, PMID: 30370017, PMCID: PMC6201794

Fu Z, Löfqvist CA, Liegl R, Wang Z, Sun Y, Gong Y, Liu CH, Meng SS, Burnim SB, Arellano I, Chouinard MT, Duran R, Poblete A, Cho SS, Akula JD, Kinter M, Ley D, Pupp IH, Talukdar S, Hellström A, Smith LE. Photoreceptor glucose metabolism determines normal retinal vascular growth. EMBO Mol Med 10:76-90, 2018 January, PMID: 29180355, PMCID: PMC5760850

Groennebaek T, Jespersen NR, Jakobsgaard JE, Sieljacks P, Wang J, Rindom E, Musci RV, Bøtker HE, Hamilton KL, Miller BF, de Paoli FV, Vissing K. Skeletal Muscle Mitochondrial Protein Synthesis and Respiration Increase With Low-Load Blood Flow Restricted as Well as High-Load Resistance Training. Front Physiol 9:1796, 2018 December, PMID: 30618808, PMCID: PMC6304675

Hill S, Sataranatarajan K, Van Remmen H. Role of Signaling Molecules in Mitochondrial Stress Response. Front Genet 9:225, 2018 July, PMID: 30042784, PMCID: PMC6048194

Issa R, Boeving M, Kinter M, Griffin TM. Effect of biomechanical stress on endogenous antioxidant networks in bovine articular cartilage. J Orthop Res 36:760-769, 2018 February, PMID: 28892196, PMCID: PMC5839935

Kalaitzoglou E, Lopes EBP, Fu Y, Herron JC, Flaming JM, Donovan EL, Hu Y, Filiberti A, Griffin TM, Humphrey MB. TLR4 Promotes and DAP12 Limits Obesity-Induced Osteoarthritis in Aged Female Mice. JBMR Plus 3:e10079, 2018 October, PMID: 31044181, PMCID: PMC6478583

Lewis TL Jr, Kwon SK, Lee A, Shaw R, Polleux F. MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. Nat Commun 9:5008, 2018 November, PMID: 30479337, PMCID: PMC6258764

Logan S, Pharaoh GA, Marlin MC, Masser DR, Matsuzaki S, Wronowski B, Yeganeh A, Parks EE, Premkumar P, Farley JA, Owen DB, Humphries KM, Kinter M, Freeman WM, Szweda LI, Van Remmen H, Sonntag WE. Insulin-like growth factor receptor signaling regulates working memory, mitochondrial metabolism, and amyloid-β uptake in astrocytes. Mol Metab 9:141-155, 2018 March, PMID: 29398615, PMCID: PMC5870102

Lynch WB, Tschumi CW, Sharpe AL, Branch SY, Chen C, Ge G, Li S, Beckstead MJ. Progressively disrupted somatodendritic morphology in dopamine neurons in a mouse Parkinson's model. Mov Disord 33:1928-1937, 2018 December, PMID: 30440089, PMCID: PMC6492291

Plafker KS, Zyla K, Berry W, Plafker SM. Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence. Redox Biol 17:411-422, 2018 July, PMID: 29879550, PMCID: PMC6007080

Qaisar R, Bhaskaran S, Premkumar P, Ranjit R, Natarajan KS, Ahn B, Riddle K, Claflin DR, Richardson A, Brooks SV, Van Remmen H. Oxidative stress-induced dysregulation of excitation-contraction coupling contributes to muscle weakness. J Cachexia Sarcopenia Muscle 9:1003-1017, 2018 October, PMID: 30073804, PMCID: PMC6204588

Sakellariou GK, McDonagh B, Porter H, Giakoumaki II, Earl KE, Nye GA, Vasilaki A, Brooks SV, Richardson A, Van Remmen H, McArdle A, Jackson MJ. Comparison of Whole Body SOD1 Knockout with Muscle-Specific SOD1 Knockout Mice Reveals a Role for Nerve Redox Signaling in Regulation of Degenerative Pathways in Skeletal Muscle. Antioxid Redox Signal 28:275-295, 2018 February, PMID: 29065712, PMCID: PMC5743036

Schafer C, Young ZT, Makarewich CA, Elnwasany A, Kinter C, Kinter M, Szweda LI. Coenzyme A-mediated degradation of pyruvate dehydrogenase kinase 4 promotes cardiac metabolic flexibility after high-fat feeding in mice. J Biol Chem 293:6915-6924, 2018 May, PMID: 29540486, PMCID: PMC5936801

Tarantini S, Valcarcel-Ares MN, Yabluchanskiy A, Tucsek Z, Hertelendy P, Kiss T, Gautam T, Zhang XA, Sonntag WE, de Cabo R, Farkas E, Elliott MH, Kinter MT, Deak F, Ungvari Z, Csiszar A. Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype. J Gerontol A Biol Sci Med Sci 73:853-863, 2018 June, PMID: 29905772, PMCID: PMC6001893

Tschumi CW, Beckstead MJ. Neurotensin speeds inhibition of dopamine neurons through temporal modulation of GABA_A and GABA_B receptor-mediated synaptic input. Neuropharmacology 131:414-423, 2018 March, PMID: 29307543, PMCID: PMC6233987

Wang H, Sun X, Lin MS, Ferrario CM, Van Remmen H, Groban L. G protein-coupled estrogen receptor (GPER) deficiency induces cardiac remodeling through oxidative stress. Transl Res 199:39-51, 2018 September, PMID: 29758174, PMCID: PMC6151279

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