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.

2024

Borowik AK, Murach KA, Miller BF. The expanding roles of myonuclei in adult skeletal muscle health and function. Biochem Soc Trans 52:1-14, 2024 December, PMID: 39700019

Isola JVV, Biswas S, Jayarathne H, Hubbart CR, Hense JD, Matsuzaki S, Kinter MT, Humphries KM, Ocañas SR, Sadagurski M, Stout MB. Canagliflozin treatment prevents follicular exhaustion and attenuates hallmarks of ovarian aging in genetically heterogenous mice. Geroscience, 2024 December, PMID: 39672978

Griffin TM, Lopes EBP, Cortassa D, Batushansky A, Jeffries MA, Makosa D, Jopkiewicz A, Mehta-D'souza P, Komaravolu RK, Kinter MT. Sexually dimorphic metabolic effects of a high fat diet on knee osteoarthritis in mice. Biol Sex Differ 15:103, 2024 December, PMID: 39639386, PMCID: PMC11619521

Xu H, Brown JL, Bhaskaran S, Van Remmen H. Reactive oxygen species in skeletal muscle injury, fatigue, regeneration and ageing: In memory of John Faulkner. Free Radic Biol Med, 2024 November, PMID: 39613046

Ortlund E, Hou Z, Chen CY, Gaul D, Zhang T, Moore S, Liu X, Ivanova A, Maner-Smith K, Newgard C, Bodine S, Savage E, Bennett A, Fernandez F. Endurance Exercise Training Alters Lipidomic Profiles of Plasma and Eight Tissues in Rats: a MoTrPAC study. Res Sq, 2024 November, PMID: 39606465, PMCID: PMC11601870

Corder KM, Hoffman JM, Sogorovic A, Yang Y, Banerjee A, Sun Y, Stout MB, Austad SN. Negative effects of lifespan extending intervention on resilience in mice. PLoS One 19:e0312440, 2024 November, PMID: 39570905, PMCID: PMC11581327

Bhaskaran S, Piekarz KM, Brown J, Yang B, Ocañas SR, Wren JD, Georgescu C, Bottoms C, Murphy A, Thomason J, Saunders D, Smith N, Towner R, Van Remmen H. The nitrone compound OKN-007 delays motor neuron loss and disease progression in the G93A mouse model of amyotrophic lateral sclerosis. Front Neurosci 18:1505369, 2024 November, PMID: 39633896, PMCID: PMC11614777

Blankenship HE, Carter KA, Pham KD, Cassidy NT, Markiewicz AN, Thellmann MI, Sharpe AL, Freeman WM, Beckstead MJ. VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction. Nat Commun 15:9673, 2024 November, PMID: 39516200, PMCID: PMC11549218

Nguyen HVM, Ran Q, Salmon AB, Ahn B, Chiao YA, Bhaskaran S, Richardson A. Mouse Models Used to Test the Role of Reactive Oxygen Species in Aging and Age-Related Chronic Diseases. Free Radic Biol Med, 2024 October, PMID: 39419456, PMCID: PMC11624111

Zarzycka W, Kobak KA, King CJ, Peelor FF 3rd, Miller BF, Chiao YA. Hyperactive mTORC1/4EBP1 signaling dysregulates proteostasis and accelerates cardiac aging. Geroscience, 2024 October, PMID: 39379739

Ramirez-Sagredo A, Sunny AT, Cupp-Sutton KA, Chowdhury T, Zhao Z, Wu S, Chiao YA. Characterizing age-related changes in intact mitochondrial proteoforms in murine hearts using quantitative top-down proteomics. Clin Proteomics 21:57, 2024 September, PMID: 39343872, PMCID: PMC11440756

Laumonnerie C, Shamambo M, Stabley DR, Lewis TL Jr, Trivedi N, Howell D, Solecki DJ. Antagonistic action of Siah2 and Pard3/JamC to promote germinal zone exit of differentiated cerebellar granule neurons by modulating Ntn1 signaling via Dcc. Res Sq, 2024 September, PMID: 39399669, PMCID: PMC11469462

Musci RV, Fuqua JD, Peelor FF 3rd, Nguyen HVM, Richardson A, Choi S, Miller BF, Wanagat J. Age-induced changes in skeletal muscle mitochondrial DNA synthesis, quantity, and quality in genetically unique rats. Geroscience, 2024 September, PMID: 39312152

Das S, Varshney R, Farriester JW, Kyere-Davies G, Martinez AE, Hill K, Kinter M, Mullen GP, Nagareddy PR, Rudolph MC. NR2F2 Reactivation in Early-life Adipocyte Stem-like Cells Rescues Adipocyte Mitochondrial Oxidation. bioRxiv, 2024 September, PMID: 39314382, PMCID: PMC11419096

Sharpe AL, Liter LR, Donohue D, Carter KA, Vangeneugden P, Weaver S, Stout MB, Beckstead MJ. Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake. bioRxiv, 2024 September, PMID: 39282417, PMCID: PMC11398421

Kemna RE, Kueck PJ, Blankenship A, John CS, Johnson CN, Green ZD, Chamberlain T, Thyfault JP, Mahnken JD, Miller BF, Morris JK. Methods to characterize lactate turnover in aging and Alzheimer's disease; The LEAN study. Contemp Clin Trials:107682, 2024 September, PMID: 39236780

Kim H, Ranjit R, Claflin DR, Georgescu C, Wren JD, Brooks SV, Miller BF, Ahn B. Unacylated Ghrelin Protects Against Age-Related Loss of Muscle Mass and Contractile Dysfunction in Skeletal Muscle. Aging Cell:e14323, 2024 September, PMID: 39223708, PMCID: PMC11634730

Nasuhidehnavi A, Zarzycka W, Górecki I, Chiao YA, Lee CF. Emerging interactions between mitochondria and NAD( ) metabolism in cardiometabolic diseases. Trends Endocrinol Metab, 2024 August, PMID: 39198117

Sok SPM, Pipkin K, Popescu NI, Reidy M, Li B, Van Remmen H, Kinter M, Sun XH, Fan Z, Zhao M. Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis. J Immunol, 2024 August, PMID: 39158281, PMCID: PMC11408103

Hines MR, Gomez-Contreras PC, Liman S, Wilson AM, Lu KJ, O'Neill JA, Fisher JS, Fredericks DC, Wagner BA, Buettner GR, Van Remmen H, Coleman MC. A reciprocal relationship between mitochondria and lipid peroxidation determines the chondrocyte intracellular redox environment. Redox Biol 75:103306, 2024 August, PMID: 39133964, PMCID: PMC11366903

Sathiaseelan R, Isola JVV, Santín-Márquez R, Adekunbi D, Fornalik M, Salmon AB, Stout MB. A pilot study evaluating dosing tolerability of 17α-estradiol in male common marmosets (Callithrix jacchus). Geroscience, 2024 August, PMID: 39107620

Iannitelli AF, Hassenein L, Mulvey B, Blankenship HE, Liles LC, Sharpe AL, Pare JF, Segal A, Sloan SA, Martinowich K, McCann KE, Dougherty JD, Smith Y, Beckstead MJ, Weinshenker D. Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus. bioRxiv, 2024 August, PMID: 36945637, PMCID: PMC10028911

Tandon I, Woessner A, Ferreira LA, Shamblin C, Vaca-Diez G, Walls A, Kuczwara P, Applequist A, Nascimento DF, Tandon S, Kim JW, Rausch M, Timek T, Padala M, Kinter MT, Province D, Byrum SD, Quinn KP, Balachandran K. A Three-Dimensional Valve-on-Chip Microphysiological System Implicates Cell Cycle Progression, Cholesterol Metabolism and Protein Homeostasis in Early Calcific Aortic Valve Disease Progression. Acta Biomater, 2024 July, PMID: 39084496, PMCID: PMC11702842

Hense JD, Garcia DN, Zanini BM, Barreto MM, Perreira GC, Isola JVV, de Brito C, Fornalik M, Mondal SA, Ávila BM, Oliveira TL, Rice HC, Lacy CI, Vaucher RA, Mason JB, Masternak MM, Stout MB, Schneider A. MASLD does not affect fertility and senolytics fail to prevent MASLD progression in male mice. Sci Rep 14:17332, 2024 July, PMID: 39068167, PMCID: PMC11283523

Deberneh HM, Taylor ME, Borowik AK, Miyagi M, Miller BF, Sadygov RG. Numbers of Exchangeable Hydrogens from LC-MS Data of Heavy Water Metabolically Labeled Samples. J Am Soc Mass Spectrom, 2024 July, PMID: 39057601

Hense JD, Isola JVV, Garcia DN, Magalhães LS, Masternak MM, Stout MB, Schneider A. The role of cellular senescence in ovarian aging. NPJ Aging 10:35, 2024 July, PMID: 39033161, PMCID: PMC11271274

Schenk S, Sagendorf TJ, Many GM, Lira AK, de Sousa LGO, Bae D, Cicha M, Kramer KS, Muehlbauer M, Hevener AL, Rector RS, Thyfault JP, Williams JP, Goodyear LJ, Esser KA, Newgard CB, Bodine SC, MoTrPAC Study Group. Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC). Function (Oxf) 5, 2024 July, PMID: 38984994, PMCID: PMC11245678

Wood TWP, Henriques WS, Cullen HB, Romero M, Blengini CS, Sarathy S, Sorkin J, Bekele H, Jin C, Kim S, Chemiakine A, Khondker RC, Isola JVV, Stout MB, Gennarino VA, Mogessie B, Jain D, Schindler K, Suh Y, Wiedenheft B, Berchowitz LE. The retrotransposon-derived capsid genes PNMA1 and PNMA4 maintain reproductive capacity. Res Sq, 2024 July, PMID: 39041030, PMCID: PMC11261967

Higgs MH, Beckstead MJ. Impact of unitary synaptic inhibition on spike timing in ventral tegmental area dopamine neurons. eNeuro, 2024 July, PMID: 38969500, PMCID: PMC11287791

Bubak MP, Davidyan A, O'Reilly CL, Mondal SA, Keast J, Doidge SM, Borowik AK, Taylor ME, Volovičeva E, Kinter MT, Britton SL, Koch LG, Stout MB, Lewis TL Jr, Miller BF. Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities. Aging Cell:e14235, 2024 June, PMID: 38923664, PMCID: PMC11488331

Kobak KA, Batushansky A, Jopkiewicz A, Peelor FF 3rd, Kinter MT, Miller BF, Griffin TM. Effect of biological sex and short-term high-fat diet on cellular proliferation, ribosomal biogenesis, and targeted protein abundance in murine articular cartilage. Osteoarthr Cartil Open 6:100495, 2024 June, PMID: 39040627, PMCID: PMC11260562

Negri S, Sanford M, Reyff Z, Ballard C, Nyul-Toth A, Gulej R, Brown J, O'Reilly C, Van Remmen H, Csiszar A, Ungvari Z, Tarantini S. Transcriptomic signatures of time-restricted feeding (TRF) in cerebrovascular aging and cognitive health. Vascul Pharmacol 155:107338, 2024 June, PMID: 38985616

Camon C, Prescott M, Neyt C, Decourt C, Stout MB, Campbell RE, Garratt M. Systemic metabolic benefits of 17α-estradiol are not exclusively mediated by ERα in glutamatergic or GABAergic neurons. Geroscience, 2024 May, PMID: 38776045, PMCID: PMC11493872

Milan M, Brown J, O'Reilly CL, Bubak MP, Negri S, Balasubramanian P, Dhanekula AS, Pharaoh G, Reyff Z, Ballard C, Shi H, Yabluchanskiy A, Rudolph MC, Ungvari Z, Marcinek DJ, Miller BF, Van Remmen H, Tarantini S. Time-restricted feeding improves aortic endothelial relaxation by enhancing mitochondrial function and attenuating oxidative stress in aged mice. Redox Biol 73:103189, 2024 May, PMID: 38788541, PMCID: PMC11140804

Chucair-Elliott AJ, Ocañas SR, Pham K, Machalinski A, Plafker S, Stout MB, Elliott MH, Freeman WM. Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium. Neurobiol Aging 140:41-59, 2024 May, PMID: 38723422, PMCID: PMC11173338

Isola JVV, Hense JD, Osorio CAP, Biswas S, Alberola-Ila J, Ocanas SR, Schneider A, Stout MB. Inflammation, immune cells, and cellular senescence in the aging ovary. Reproduction, 2024 May, PMID: 38744316, PMCID: PMC11301429

Many GM, Sanford JA, Sagendorf TJ, Hou Z, Nigro P, Whytock KL, Amar D, Caputo T, Gay NR, Gaul DA, Hirshman MF, Jimenez-Morales D, Lindholm ME, Muehlbauer MJ, Vamvini M, Bergman BC, Fernández FM, Goodyear LJ, Hevener AL, Ortlund EA, Sparks LM, Xia A, Adkins JN, Bodine SC, Newgard CB, Schenk S, MoTrPAC Study Group. Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue. Nat Metab, 2024 May, PMID: 38693320, PMCID: PMC11132991

Amar D, Gay NR, Jimenez-Morales D, Jean Beltran PM, Ramaker ME, Raja AN, Zhao B, Sun Y, Marwaha S, Gaul DA, Hershman SG, Ferrasse A, Xia A, Lanza I, Fernández FM, Montgomery SB, Hevener AL, Ashley EA, Walsh MJ, Sparks LM, Burant CF, Rector RS, Thyfault J, Wheeler MT, Goodpaster BH, Coen PM, Schenk S, Bodine SC, Lindholm ME, MoTrPAC Study Group. The mitochondrial multi-omic response to exercise training across rat tissues. Cell Metab, 2024 April, PMID: 38701776, PMCID: PMC11152996

Chakraborty P, Niewiadomska M, Farhat K, Morris L, Whyte S, Humphries KM, Stavrakis S. Effect of Low-Level Tragus Stimulation on Cardiac Metabolism in Heart Failure with Preserved Ejection Fraction: A Transcriptomics-Based Analysis. Int J Mol Sci 25, 2024 April, PMID: 38673896, PMCID: PMC11050145

Harold KM, Matsuzaki S, Pranay A, Loveland BL, Batushansky A, Mendez Garcia MF, Eyster C, Stavrakis S, Chiao YA, Kinter M, Humphries KM. Loss of Cardiac PFKFB2 Drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart. J Am Heart Assoc 13:e033676, 2024 April, PMID: 38533937, PMCID: PMC11179765

Chen J, Ding Y, Jiang C, Qu R, Wren JD, Georgescu C, Wang X, Reuter DN, Liu B, Giles CB, Mayr CH, Schiller HB, Dai J, Stipp CS, Subramaniyan B, Wang J, Zuo H, Huang C, Fung KM, Rice HC, Sonnenberg A, Wu D, Walters MS, Zhao YY, Kanie T, Hays FA, Papin JF, Wang DW, Zhang XA. CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation. Circ Res, 2024 April, PMID: 38557119, PMCID: PMC11081830

Noh JY, Farhataziz N, Kinter MT, Yan X, Sun Y. Colonic Dysregulation of Major Metabolic Pathways in Experimental Ulcerative Colitis. Metabolites 14, 2024 March, PMID: 38668322, PMCID: PMC11052278

Xu H, Piekarz KM, Brown JL, Bhaskaran S, Smith N, Towner RA, Van Remmen H. Neuroprotective treatment with the nitrone compound OKN-007 mitigates age-related muscle weakness in aging mice. Geroscience, 2024 March, PMID: 38512579, PMCID: PMC11336152

Palakshappa JA, Batt JAE, Bodine SC, Connolly BA, Doles J, Falvey JR, Ferrante LE, Files DC, Harhay MO, Harrell K, Hippensteel JA, Iwashyna TJ, Jackson JC, Lane-Fall MB, Monje M, Moss M, Needham DM, Semler MW, Lahiri S, Larsson L, Sevin CM, Sharshar T, Singer B, Stevens T, Taylor SP, Gomez CR, Zhou G, Girard TD, Hough CL. Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: National Heart, Lung, and Blood Institute Workshop Report. Am J Respir Crit Care Med, 2024 March, PMID: 38477657, PMCID: PMC11146564

Virga DM, Hamilton S, Osei B, Morgan A, Kneis P, Zamponi E, Park NJ, Hewitt VL, Zhang D, Gonzalez KC, Russell FM, Grahame Hardie D, Prudent J, Bloss E, Losonczy A, Polleux F, Lewis TL Jr. Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo. Nat Commun 15:2142, 2024 March, PMID: 38459070, PMCID: PMC10923867

Hinton A Jr, Katti P, Mungai M, Hall DD, Koval O, Shao J, Vue Z, Lopez EG, Rostami R, Neikirk K, Ponce J, Streeter J, Schickling B, Bacevac S, Grueter C, Marshall A, Beasley HK, Do Koo Y, Bodine SC, Nava NGR, Quintana AM, Song LS, Grumbach IM, Pereira RO, Glancy B, Abel ED. ATF4-dependent increase in mitochondrial-endoplasmic reticulum tethering following OPA1 deletion in skeletal muscle. J Cell Physiol, 2024 February, PMID: 38419397, PMCID: PMC11144302

Ohene-Marfo P, Nguyen HVM, Mohammed S, Thadathil N, Tran A, Nicklas EH, Wang D, Selvarani R, Farriester JW, Varshney R, Kinter M, Richardson A, Rudolph MC, Deepa SS. Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model. Int J Mol Sci 25, 2024 February, PMID: 38474061, PMCID: PMC10931720

Hirabayashi Y, Lewis TL Jr, Du Y, Virga DM, Decker AM, Coceano G, Alvelid J, Paul MA, Hamilton S, Kneis P, Takahashi Y, Gaublomme JT, Testa I, Polleux F. Most axonal mitochondria in cortical pyramidal neurons lack mitochondrial DNA and consume ATP. bioRxiv, 2024 February, PMID: 38405915, PMCID: PMC10888904

Deepa SS, Thadathil N, Corral J, Mohammed S, Pham S, Rose H, Kinter MT, Richardson A, Díaz-García CM. MLKL overexpression leads to Ca(2 ) and metabolic dyshomeostasis in a neuronal cell model. Cell Calcium 119:102854, 2024 February, PMID: 38430790, PMCID: PMC10990772

Veiga GB, Zanini BM, Garcia DN, Hense JD, Barreto MM, Isola JVV, Mondadori RG, Masternak MM, Stout MB, Schneider A. Effects of calorie, protein, and branched chain amino acid restriction on ovarian aging in mice. Reprod Biol 24:100856, 2024 January, PMID: 38295721, PMCID: PMC10978239

Larson KR, Jayakrishnan D, Soto Sauza KA, Goodson ML, Chaffin AT, Davidyan A, Pathak S, Fang Y, Gonzalez Magaña D, Miller BF, Ryan KK. FGF21 induces skeletal muscle atrophy and increases amino acids in female mice: a potential role for glucocorticoids. Endocrinology, 2024 January, PMID: 38244215, PMCID: PMC10849119

Muñoz-Oreja M, Sandoval A, Bruland O, Perez-Rodriguez D, Fernandez-Pelayo U, de Arbina AL, Villar-Fernandez M, Hernández-Eguiazu H, Hernández I, Park Y, Goicoechea L, Pascual-Frías N, Garcia-Ruiz C, Fernandez-Checa J, Martí-Carrera I, Gil-Bea FJ, Hasan MT, Gegg ME, Bredrup C, Knappskog PM, Gereñu-Lopetegui G, Varhaug KN, Bindoff LA, Spinazzola A, Yoon WH, Holt IJ. Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation. Brain, 2024 January, PMID: 38242545, PMCID: PMC11068212

Borowik AK, Lawrence MM, Peelor FF 3rd, Piekarz KM, Crosswhite A, Richardson A, Miller BF, Van Remmen H, Brown JL. Senolytic treatment does not mitigate oxidative stress-induced muscle atrophy but improves muscle force generation in CuZn superoxide dismutase knockout mice. Geroscience, 2024 January, PMID: 38233728, PMCID: PMC11009189

Isola JVV, Ocañas SR, Hubbart CR, Ko S, Mondal SA, Hense JD, Carter HNC, Schneider A, Kovats S, Alberola-Ila J, Freeman WM, Stout MB. A single-cell atlas of the aging mouse ovary. Nat Aging, 2024 January, PMID: 38200272, PMCID: PMC10798902

Bubak MP, Mann SN, Borowik AK, Pranay A, Batushansky A, Vieira de Sousa Neto I, Ali Mondal SA, Doidge SM, Davidyan A, Szczygiel MM, Peelor Iii FF, Rigsby S, Broomfield ME, Lacy CI, Rice HC, Stout MB, Miller BF. 17α-estradiol Alleviates High-Fat Diet-Induced Inflammatory and Metabolic Dysfunction in Skeletal Muscle of Male and Female Mice. Am J Physiol Endocrinol Metab, 2024 January, PMID: 38197793, PMCID: PMC11193529

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