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 & 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.

2023

Czyżowska A, Brown J, Xu H, Sataranatarajan K, Kinter M, Tyrell VJ, O'Donnell VB, Van Remmen H. Elevated phospholipid hydroperoxide glutathione peroxidase (GPX4) expression modulates oxylipin formation and inhibits age-related skeletal muscle atrophy and weakness. Redox Biol 64:102761, 2023 June, PMID: 37279604

Garcia DN, Hense JD, Zanini BM, Isola JVV, Pradiee J, Prosczek JB, Alvarado-Rincón JA, Mondadori RG, Mason JB, Brieño-Enríquez MA, Barros CC, Stout MB, Masternak MM, Schneider A. Dasatinib and quercetin increase testosterone and sperm concentration in mice. Physiol Int, 2023 May, PMID: 37235453

Mohammed S, Thadathil N, Ohene-Marfo P, Tran AL, Van Der Veldt M, Georgescu C, Oh S, Nicklas EH, Wang D, Haritha NH, Luo W, Janknecht R, Miller BF, Wren JD, Freeman WM, Deepa SS. Absence of either Ripk3 or Mlkl reduces incidence of hepatocellular carcinoma independent of liver fibrosis. Mol Cancer Res, 2023 May, PMID: 37204757

Bruns DR, McNair BD, Peelor FF 3rd, Borowik AK, Pranay A, Yusifov A, Miller BF. Skeletal and cardiac muscle have different protein turnover responses in a model of right heart failure. Geroscience, 2023 April, PMID: 37118350

Plafker SM, Titcomb T, Zyla-Jackson K, Kolakowska A, Wahls T. Overview of diet and autoimmune demyelinating optic neuritis: a narrative review. Immunometabolism (Cobham) 5:e00022, 2023 April, PMID: 37128292, PMCID: PMC10144304

Geraghty T, Obeidat AM, Ishihara S, Wood MJ, Li J, Lopes EBP, Scanzello CR, Griffin TM, Malfait AM, Miller RE. Age-associated changes in knee osteoarthritis, pain-related behaviors, and dorsal root ganglia immunophenotyping of male and female mice. Arthritis Rheumatol, 2023 April, PMID: 37096632

Deberneh HM, Abdelrahman DR, Verma SK, Linares JJ, Murton AJ, Russell WK, Kuyumcu-Martinez MN, Miller BF, Sadygov RG. Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling. Commun Chem 6:72, 2023 April, PMID: 37069333, PMCID: PMC10110577

Panda A, Suvakov M, Mariani J, Drucker KL, Park Y, Jang Y, Kollmeyer TM, Sarkar G, Bae T, Kim JJ, Yoon WH, Jenkins RB, Vaccarino FM, Abyzov A. Clonally Selected Lines After CRISPR-Cas Editing Are Not Isogenic. CRISPR J 6:176-182, 2023 April, PMID: 37071670, PMCID: PMC10123805

Jonsson WO, Borowik AK, Pranay A, Kinter MT, Mirek ET, Levy JL, Snyder EM, Miller BF, Anthony TG. Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction. Geroscience, 2023 March, PMID: 36976488

Higgs MH, Jones JA, Wilson CJ, Beckstead MJ. SK and Kv4 channels limit spike timing perturbations in pacemaking dopamine neurons. eNeuro, 2023 March, PMID: 36973012, PMCID: PMC10088984

Stout MB, Vaughan KL, Isola JVV, Mann SN, Wellman B, Hoffman JM, Porter HL, Freeman WM, Mattison JA. Assessing tolerability and physiological responses to 17α-estradiol administration in male rhesus macaques. Geroscience, 2023 March, PMID: 36897526

Zyla-Jackson K, Walton DA, Plafker KS, Kovats S, Georgescu C, Brush RS, Tytanic M, Agbaga MP, Plafker SM. Dietary protection against the visual and motor deficits induced by experimental autoimmune encephalomyelitis. Front Neurol 14:1113954, 2023 March, PMID: 36937529, PMCID: PMC10017782

Campbell MD, Samuelson AT, Chiao YA, Sweetwyne MT, Ladiges WC, Rabinovitch PS, Marcinek DJ. Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice. Geroscience, 2023 February, PMID: 36840897

Wang J, Mogensen AG, Thybo F, Brandbyge M, Jensen JB, van Hall G, Agergaard J, de Paoli FV, Miller BF, Bøtker HE, Farup J, Vissing K. Low-load blood flow-restricted resistance exercise produce fiber type-independent hypertrophy and improves muscle functional capacity in older individuals. J Appl Physiol (1985), 2023 February, PMID: 36825645

Ocañas SR, Isola JVV, Saccon TD, Pham KD, Chucair-Elliott AJ, Schneider A, Freeman WM, Stout MB. Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome. J Vis Exp, 2023 February, PMID: 36912526, PMCID: PMC10165884

Pollock N, Macpherson PC, Staunton CA, Hemmings K, Davis CS, Owen ED, Vasilaki A, Van Remmen H, Richardson A, McArdle A, Brooks SV, Jackson MJ. Deletion of Sod1 in motor neurons exacerbates age-related changes in axons and neuromuscular junctions in mice. eNeuro, 2023 February, PMID: 36810149, PMCID: PMC10026931

Sathiaseelan R, Ahn B, Stout MB, Logan S, Wanagat J, Van M Nguyen H, Hord NG, Vandiver AR, Selvarani R, Ranjit R, Yarbrough H, Masingale A, Miller BF, Wolf RF, Austad SN, Richardson A. A Genetically Heterogeneous Rat Model with Divergent Mitochondrial Genomes. J Gerontol A Biol Sci Med Sci, 2023 February, PMID: 36762848, PMCID: PMC10172978

Barnes JN, Burns JM, Bamman MM, Billinger SA, Bodine SC, Booth FW, Brassard P, Clemons TA, Fadel PJ, Geiger PC, Gujral S, Haus JM, Kanoski SE, Miller BF, Morris JK, O'Connell KMS, Poole DC, Sandoval DA, Smith JC, Swerdlow RH, Whitehead SN, Vidoni ED, van Praag H. Proceedings from the Albert Charitable Trust Inaugural Workshop on 'Understanding the Acute Effects of Exercise on the Brain'. Brain Plast 8:153-168, 2023 February, PMID: 36721393, PMCID: PMC9837736

Chusyd DE, Brown JL, Golzarri-Arroyo L, Dickinson SL, Kraus VB, Siegal-Willott J, Griffin TM, Huebner JL, Edwards KL, Allison DB, Austad SN. Relationship between reproductive and bone biomarkers and osteoarthritis in zoo asian (elephas maximus) and African (loxodonta africana) elephants J Zoo Wildl Med 53:801-810, 2023 January, PMID: 36640083, PMCID: PMC10150656

Dominguez-Lopez S, Ahn B, Sataranatarajan K, Ranjit R, Premkumar P, Van Remmen H, Beckstead MJ. Long-term methamphetamine self-administration increases mesolimbic mitochondrial oxygen consumption and decreases striatal glutathione. Neuropharmacology:109436, 2023 January, PMID: 36693561, PMCID: PMC10080784

Troyano-Rodriguez E, Blankenship HE, Handa K, Branch SY, Beckstead MJ. Preservation of dendritic D2 receptor transmission in substantia nigra dopamine neurons with age. Sci Rep 13:1025, 2023 January, PMID: 36658269, PMCID: PMC9852430

2022

O'Reilly CL, Miller BF, Lewis TL Jr. Exercise and mitochondrial remodeling to prevent age-related neurodegeneration. J Appl Physiol (1985), 2022 December, PMID: 36519568, PMCID: PMC9829476

Whittle EF, Chilian M, Karimiani EG, Progri H, Buhas D, Kose M, Ganetzky RD, Toosi MB, Torbati PN, Badv RS, Shelihan I, Yang H, Elloumi HZ, Lee S, Jamshidi Y, Pittman AM, Houlden H, Ignatius E, Rahman S, Maroofian R, Yoon WH, Carroll CJ. Biallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. Genet Med, 2022 December, PMID: 36520152, PMCID: PMC9905285

Ali Mondal S, Sathiaseelan R, Mann SN, Kamal M, Luo W, Saccon TD, Isola JV, Peelor FF 3rd, Li T, Freeman WF, Miller BF, Stout MB. 17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice. Am J Physiol Endocrinol Metab, 2022 December, PMID: 36516471, PMCID: PMC9902223

Li P, Newhardt MF, Matsuzaki S, Eyster C, Pranay A, Peelor FF 3rd, Batushansky A, Kinter C, Subramani K, Subrahmanian S, Ahamed J, Yu P, Kinter M, Miller BF, Humphries KM. The loss of cardiac SIRT3 decreases metabolic flexibility and proteostasis in an age-dependent manner. Geroscience, 2022 December, PMID: 36460774, PMCID: PMC9886736

Ranjit R, Van Remmen H, Ahn B. Acylated Ghrelin Receptor Agonist HM01 Decreases Lean Body and Muscle Mass, but Unacylated Ghrelin Protects against Redox-Dependent Sarcopenia. Antioxidants (Basel) 11, 2022 November, PMID: 36552566, PMCID: PMC9774605

Curl CC, Kumar A, Peck AJ, Arevalo JA, Gleason A, Leija RG, Osmond AD, Duong JJ, Miller BF, Horning MA, Brooks GA. Fractional Gluconeogenesis: A Biomarker of Dietary Energy Adequacy in a Rat Brain Injury Model. Metabolites 12, 2022 November, PMID: 36557201, PMCID: PMC9781857

Borowik AK, Davidyan A, Peelor FF 3rd, Voloviceva E, Doidge SM, Bubak MP, Mobley CB, McCarthy JJ, Dupont-Versteegden EE, Miller BF. Skeletal Muscle Nuclei in Mice are not Post-mitotic. Function (Oxf) 4:zqac059, 2022 November, PMID: 36569816, PMCID: PMC9772608

Xu H, Ahn B, Van Remmen H. Impact of aging and oxidative stress on specific components of excitation contraction coupling in regulating force generation. Sci Adv 8:eadd7377, 2022 October, PMID: 36288318, PMCID: PMC9604602

Drumond-Bock AL, Cybula M, Wang L, Wang L, Bieniasz M. Cloning BRD4 long isoform into overexpression vectors for stable overexpression of BRD4-L in mammalian cells. STAR Protoc 3:101785, 2022 October, PMID: 36317179, PMCID: PMC9617197

Brown JL, Peelor FF 3rd, Georgescu C, Wren JD, Kinter M, Tyrrell VJ, O'Donnell VB, Miller BF, Van Remmen H. Lipid hydroperoxides and oxylipins are mediators of denervation induced muscle atrophy. Redox Biol 57:102518, 2022 October, PMID: 36283174, PMCID: PMC9593840

Wang L, Cybula M, Rostworowska M, Wang L, Mucha P, Bulicz M, Bieniasz M. Upregulation of Succinate Dehydrogenase (SDHA) Contributes to Enhanced Bioenergetics of Ovarian Cancer Cells and Higher Sensitivity to Anti-Metabolic Agent Shikonin. Cancers (Basel) 14, 2022 October, PMID: 36291881, PMCID: PMC9599980

Qi X, Walton DA, Plafker KS, Boulton ME, Plafker SM. Sulforaphane recovers cone function in an Nrf2-dependent manner in middle-aged mice undergoing RPE oxidative stress. Mol Vis 28:378-393, 2022 October, PMID: 36338670, PMCID: PMC9603948

Zhu S, Donovan EL, Makosa D, Mehta-D'souza P, Jopkiewicz A, Batushansky A, Cortassa D, Simmons AD, Lopes EBP, Kinter M, Griffin TM. Sirt3 promotes chondrogenesis, chondrocyte mitochondrial respiration and the development of high-fat diet-induced osteoarthritis in mice. J Bone Miner Res, 2022 October, PMID: 36214465, PMCID: PMC10091721

Strong R, Miller RA, Cheng CJ, Nelson JF, Gelfond J, Allani SK, Diaz V, Dorigatti AO, Dorigatti J, Fernandez E, Galecki A, Ginsburg B, Hamilton KL, Javors MA, Kornfeld K, Kaeberlein M, Kumar S, Lombard DB, Lopez-Cruzan M, Miller BF, Rabinovitch P, Reifsnyder P, Rosenthal NA, Bogue MA, Salmon AB, Suh Y, Verdin E, Weissbach H, Newman J, Maccchiarini F, Harrison DE. Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice. Aging Cell:e13724, 2022 September, PMID: 36179270, PMCID: PMC9741502

Perez-Bonilla P, Ramirez-Virella J, Menon P, Troyano-Rodriguez E, Arriaga SK, Makela A, Bugescu R, Beckstead MJ, Leinninger GM. Developmental or adult-onset deletion of neurotensin receptor-1 from dopamine neurons differentially reduces body weight. Front Neurosci 16:874316, 2022 September, PMID: 36213756, PMCID: PMC9537700

Hossen MN, Wang L, Dwivedi SKD, Zhang Y, Rao G, Elechalwar CK, Sheth V, Dey A, Asfa S, Gulla SK, Xu C, Fung KM, Robertson JD, Bieniasz M, Wilhelm S, Bhattacharya R, Mukherjee P. Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth. Adv Sci (Weinh):e2200491, 2022 September, PMID: 36104215, PMCID: PMC9631030

Nizami HL, Minor KE, Chiao YA, Light CM, Lee CF. Sexually Dimorphic Effects of SARM1 Deletion on Cardiac NAD Metabolism and Function. Am J Physiol Heart Circ Physiol, 2022 September, PMID: 36053750, PMCID: PMC9529255

Thadathil N, Selvarani R, Mohammed S, Nicklas EH, Tran AL, Kamal M, Luo W, Brown JL, Lawrence MM, Borowik AK, Miller BF, Van Remmen H, Richardson A, Deepa SS. Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma. Aging Cell, 2022 July, PMID: 35869934, PMCID: PMC9381894

Rajala A, Teel K, Bhat MA, Batushansky A, Griffin TM, Purcell L, Rajala RVS. Insulin-like growth factor 1 receptor mediates photoreceptor neuroprotection. Cell Death Dis 13:613, 2022 July, PMID: 35840554, PMCID: PMC9287313

Tschumi CW, Blankenship HE, Sharma R, Lynch WB, Beckstead MJ. Neurotensin Release from Dopamine Neurons Drives Long-Term Depression of Substantia Nigra Dopamine Signaling. J Neurosci, 2022 July, PMID: 35794014, PMCID: PMC9374153

Baier MP, Nagaraja RY, Yarbrough HP, Owen DB, Masingale AM, Ranjit R, Stiles MA, Murphy A, Agbaga MP, Ahmad M, Sherry DM, Kinter MT, Van Remmen H, Logan S. Selective ablation of Sod2 in astrocytes induces sex-specific effects on cognitive function, D-serine availability, and astrogliosis. J Neurosci, 2022 June, PMID: 35760531, PMCID: PMC9351643

Chilian M, Vargas Parra K, Sandoval A, Ramirez J, Yoon WH. CRISPR/Cas9-mediated tissue-specific knockout and cDNA rescue using sgRNAs that target exon-intron junctions in Drosophila melanogaster. STAR Protoc 3:101465, 2022 June, PMID: 35719725, PMCID: PMC9204798

Isola JVV, Veiga GB, de Brito CRC, Alvarado-Rincón JA, Garcia DN, Zanini BM, Hense JD, Vieira AD, Garratt M, Gasperin BG, Schneider A, Stout MB. 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. Geroscience, 2022 June, PMID: 35689785

Murphy MP, Bayir H, Belousov V, Chang CJ, Davies KJA, Davies MJ, Dick TP, Finkel T, Forman HJ, Janssen-Heininger Y, Gems D, Kagan VE, Kalyanaraman B, Larsson NG, Milne GL, Nyström T, Poulsen HE, Radi R, Van Remmen H, Schumacker PT, Thornalley PJ, Toyokuni S, Winterbourn CC, Yin H, Halliwell B. Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo. Nat Metab 4:651-662, 2022 June, PMID: 35760871, PMCID: PMC9711940

Ocañas SR, Ansere VA, Tooley KB, Hadad N, Chucair-Elliott AJ, Stanford DR, Rice S, Wronowski B, Pham KD, Hoffman JM, Austad SN, Stout MB, Freeman WM. Differential Regulation of Mouse Hippocampal Gene Expression Sex Differences by Chromosomal Content and Gonadal Sex. Mol Neurobiol, 2022 May, PMID: 35589920, PMCID: PMC9119800

Chakraborty A, Minor KE, Nizami HL, Chiao YA, Lee CF. Harnessing NAD Metabolism as Therapy for Cardiometabolic Diseases. Curr Heart Fail Rep, 2022 May, PMID: 35556214, PMCID: PMC9339518

Xu H, Bhaskaran S, Piekarz KM, Ranjit R, Bian J, Kneis P, Ellis A, Bhandari S, Rice HC, Van Remmen H. Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer's Disease. Front Aging Neurosci 14:876816, 2022 April, PMID: 35547624, PMCID: PMC9083113

Hense JD, Garcia DN, Isola JV, Alvarado-Rincón JA, Zanini BM, Prosczek JB, Stout MB, Mason JB, Walsh PT, Brieño-Enríquez MA, Schadock I, Barros CC, Masternak MM, Schneider A. Senolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary. Geroscience, 2022 April, PMID: 35460445, PMCID: PMC9213603

Hettinger ZR, Wen Y, Peck BD, Hamagata K, Confides AL, Van Pelt DW, Harrison DA, Miller BF, Butterfield TA, Dupont-Versteegden EE. Mechanotherapy Reprograms Aged Muscle Stromal Cells to Remodel the Extracellular Matrix during Recovery from Disuse. Function (Oxf) 3:zqac015, 2022 March, PMID: 35434632, PMCID: PMC9009398

Cybula M, Bieniasz M. Patient-derived tumor models are attractive tools to repurpose drugs for ovarian cancer treatment: pre-clinical updates. Oncotarget 13:553-575, 2022 March, PMID: 35359749, PMCID: PMC8959092

Dey A, Dhar Dwivedi SK, Wang L, Hossen MN, Neizer-Ashun F, Bieniasz M, Mukherjee P, Baird JD, Weetall M, Bhattacharya R. Targeting BMI1 mitigates chemoresistance in ovarian cancer. Genes Dis 9:1415-1418, 2022 March, PMID: 36157476, PMCID: PMC9485277

Liu H, Witzigreuter L, Sathiaseelan R, Agbaga MP, Brush RS, Stout MB, Zhu S. Obesity promotes lipid accumulation in mouse cartilage-A potential role of acetyl-CoA carboxylase (ACC) mediated chondrocyte de novo lipogenesis. J Orthop Res, 2022 March, PMID: 35279877, PMCID: PMC9647658

Kobak KA, Batushansky A, Borowik AK, Lopes EPB, Peelor Iii FF, Donovan EL, Kinter MT, Miller BF, Griffin TM. An In Vivo Stable Isotope Labeling Method to Investigate Individual Matrix Protein Synthesis, Ribosomal Biogenesis, and Cellular Proliferation in Murine Articular Cartilage. Function (Oxf) 3:zqac008, 2022 February, PMID: 35399495, PMCID: PMC8991031

Ahn B, Ranjit R, Kneis P, Xu H, Piekarz KM, Freeman WM, Kinter M, Richardson A, Ran Q, Brooks SV, Van Remmen H. Scavenging mitochondrial hydrogen peroxide by peroxiredoxin 3 overexpression attenuates contractile dysfunction and muscle atrophy in a murine model of accelerated sarcopenia. Aging Cell:e13569, 2022 February, PMID: 35199907, PMCID: PMC8920438

Kobak KA, Zarzycka W, Chiao YA. Age and Sex Differences in Heart Failure With Preserved Ejection Fraction. Front Aging 3:811436, 2022 February, PMID: 35821846, PMCID: PMC9261310

Guzman SD, Judge J, Shigdar SM, Paul TA, Davis CS, Macpherson PC, Markworth JF, Van Remmen H, Richardson A, McArdle A, Brooks SV. Removal of p16 INK4 Expressing Cells in Late Life has Moderate Beneficial Effects on Skeletal Muscle Function in Male Mice. Front Aging 2:821904, 2022 January, PMID: 35821997, PMCID: PMC9261355

Isola JVV, Zanini BM, Hense JD, Alvarado-Rincón JA, Garcia DN, Pereira GC, Vieira AD, Oliveira TL, Collares T, Gasperin BG, Stout MB, Schneider A. Mild calorie restriction, but not 17α-estradiol, extends ovarian reserve and fertility in female mice. Exp Gerontol 159:111669, 2022 January, PMID: 35032571, PMCID: PMC8920046

Piekarz KM, Georgescu C, Wren JD, Towner RA, Van Remmen H. Pharmacologic treatment with OKN-007 reduces alpha-motor neuron loss in spinal cord of aging mice. Geroscience, 2022 January, PMID: 34984634, PMCID: PMC8811061

Aging & 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