Aging & Metabolism Research Program
What We Do
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.
Our Scientists
Our Publications
2022
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
Bubak MP, Mann SN, Broomfield ME, Stout MB, Miller BF. 17α-Estradiol Mitigates the Negative Effects of High-Fat Feeding in Both Male and Female Mice. FASEB J 36 Suppl 1, 2022 May, PMID: 35555322
Davidyan A, Bubak MP, Koch LG, Lewis TL Jr, Miller BF. Intrinsic Mitochondrial Function Impacts the Outcomes of Metformin Treatment on Skeletal Muscle Mitochondrial Morphology in Aged Rat. FASEB J 36 Suppl 1, 2022 May, PMID: 35560636
Sklivas AB, Rose S, Abbott C, Miller B, Butterfield T, Dupont-Versteegden E. Mechanotherapy does not Enhance Recovery Following Muscle Disuse Atrophy in Female Rats. FASEB J 36 Suppl 1, 2022 May, PMID: 35553587
Borowik AK, Peelor FF, Dupont-Versteegden EE, McCarthy JJ, Miller BF. Myonuclei Can Replicate DNA. FASEB J 36 Suppl 1, 2022 May, PMID: 35556122
Fuqua JD, Lawrence MM, Hettinger Z, Borowik AK, Peelor FF 3rd, Confides AL, Dupont-Versteegden EE, Miller BF. Impaired Proteostasis, not Protein Synthesis, Limits Recovery of Aged Skeletal Muscle After Disuse Atrophy. FASEB J 36 Suppl 1, 2022 May, PMID: 35556377
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
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
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
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
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
2021
Cybula M, Wang L, Wang L, Drumond-Bock AL, Moxley KM, Benbrook DM, Gunderson-Jackson C, Ruiz-Echevarria MJ, Bhattacharya R, Mukherjee P, Bieniasz M. Patient-Derived Xenografts of High-Grade Serous Ovarian Cancer Subtype as a Powerful Tool in Pre-Clinical Research. Cancers (Basel) 13, 2021 December, PMID: 34944908, PMCID: PMC8699796
Kumari S, Bubak M, Schoenberg HM, Davidyan A, Elliehausen CJ, Kuhn KG, VanWagoner TM, Karaman R, Scofield RH, Miller BF, Konopka AR. Antecedent Metabolic Health and Metformin (ANTHEM) Aging study: Rationale and study design for a randomized controlled trial. J Gerontol A Biol Sci Med Sci, 2021 December, PMID: 34865016
Sharpe AL, Trzeciak M, Eliason NL, Blankenship HE, Byrd BAM, Douglas PD, Freeman WM, Beckstead MJ. Repeated cocaine or methamphetamine treatment alters astrocytic CRF2 and GLAST expression in the ventral midbrain. Addict Biol:e13120, 2021 November, PMID: 34825430
Yap ZY, Efthymiou S, Seiffert S, Vargas Parra K, Lee S, Nasca A, Maroofian R, Schrauwen I, Pendziwiat M, Jung S, Bhoj E, Striano P, Mankad K, Vona B, Cuddapah S, Wagner A, Alvi JR, Davoudi-Dehaghani E, Fallah MS, Gannavarapu S, Lamperti C, Legati A, Murtaza BN, Nadeem MS, Rehman MU, Saeidi K, Salpietro V, von Spiczak S, Sandoval A, Zeinali S, Zeviani M, Reich A, SYNaPS Study Group., University of Washington Center for Mendelian Genomics., Jang C, Helbig I, Barakat TS, Ghezzi D, Leal SM, Weber Y, Houlden H, Yoon WH. Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia. Am J Hum Genet, 2021 November, PMID: 34800363, PMCID: PMC8715183
Xu H, Van Remmen H. The SarcoEndoplasmic Reticulum Calcium ATPase (SERCA) pump: a potential target for intervention in aging and skeletal muscle pathologies. Skelet Muscle 11:25, 2021 November, PMID: 34772465, PMCID: PMC8588740
Drumond-Bock AL, Bieniasz M. The role of distinct BRD4 isoforms and their contribution to high-grade serous ovarian carcinoma pathogenesis. Mol Cancer 20:145, 2021 November, PMID: 34758842, PMCID: PMC8579545
Wu D, Eeda V, Undi RB, Mann S, Stout M, Lim HY, Wang W. A Novel Peroxisome Proliferator-Activated Receptor Gamma Ligand Improves Insulin Sensitivity and Promotes Browning of White Adipose Tissue in Obese Mice. Mol Metab:101363, 2021 October, PMID: 34710641, PMCID: PMC8627988
Daneshgar N, Baguley AW, Liang PI, Wu F, Chu Y, Kinter MT, Benavides GA, Johnson MS, Darley-Usmar V, Zhang J, Chan KS, Dai DF. Metabolic derangement in polycystic kidney disease mouse models is ameliorated by mitochondrial-targeted antioxidants. Commun Biol 4:1200, 2021 October, PMID: 34671066, PMCID: PMC8528863
Su Y, Claflin DR, Huang M, Davis CS, Macpherson PCD, Richardson A, Van Remmen H, Brooks SV. Deletion of Neuronal CuZnSOD Accelerates Age-Associated Muscle Mitochondria and Calcium Handling Dysfunction That Is Independent of Denervation and Precedes Sarcopenia. Int J Mol Sci 22, 2021 October, PMID: 34639076, PMCID: PMC8509582
Van Remmen H, Freeman WM, Miller BF, Kinter M, Wren JD, Chiao A, Towner RA, Snider TA, Sonntag WE, Richardson A. Oklahoma Nathan Shock Aging Center - assessing the basic biology of aging from genetics to protein and function. Geroscience, 2021 October, PMID: 34606039, PMCID: PMC8599778
Xu H, Ranjit R, Richardson A, Van Remmen H. Muscle mitochondrial catalase expression prevents neuromuscular junction disruption, atrophy, and weakness in a mouse model of accelerated sarcopenia. J Cachexia Sarcopenia Muscle, 2021 September, PMID: 34559475, PMCID: PMC8718066
Matsuzaki S, Eyster C, Newhardt MF, Giorgione JR, Kinter C, Young ZT, Kinter M, Humphries KM. Insulin signaling alters antioxidant capacity in the diabetic heart. Redox Biol 47:102140, 2021 September, PMID: 34560411, PMCID: PMC8473541
Batushansky A, Zhu S, Komaravolu RK, South S, Mehta-D'souza P, Griffin TM. Fundamentals of OA. An initiative of Osteoarthritis and Cartilage. Chapter 9: Obesity and metabolic factors in OA. Osteoarthritis Cartilage, 2021 September, PMID: 34537381, PMCID: PMC8926936
Thadathil N, Nicklas EH, Mohammed S, Lewis TL Jr, Richardson A, Deepa SS. Necroptosis increases with age in the brain and contributes to age-related neuroinflammation. Geroscience, 2021 September, PMID: 34515928, PMCID: PMC8599532
Edwards SL, Erdenebat P, Morphis AC, Kumar L, Wang L, Chamera T, Georgescu C, Wren JD, Li J. Insulin/IGF-1 signaling and heat stress differentially regulate HSF1 activities in germline development. Cell Rep 36:109623, 2021 August, PMID: 34469721, PMCID: PMC8442575
Kobak KA, Lawrence MM, Pharaoh G, Borowik AK, Peelor FF 3rd, Shipman PD, Griffin TM, Van Remmen H, Miller BF. Determining the contributions of protein synthesis and breakdown to muscle atrophy requires non-steady-state equations. J Cachexia Sarcopenia Muscle, 2021 August, PMID: 34418329, PMCID: PMC8718081
Chiao YA, Chakraborty AD, Light CM, Tian R, Sadoshima J, Shi X, Gu H, Lee CF. NAD Redox Imbalance in the Heart Exacerbates Diabetic Cardiomyopathy. Circ Heart Fail:CIRCHEARTFAILURE120008170, 2021 August, PMID: 34374300
Rossetti ML, Dunlap KR, Salazar G, Hickner RC, Kim JS, Chase BP, Miller BF, Gordon BS. Systemic delivery of a mitochondria targeted antioxidant partially preserves limb muscle mass and grip strength in response to androgen deprivation. Mol Cell Endocrinol 535:111391, 2021 July, PMID: 34245847, PMCID: PMC8403153
Griesel BA, Matsuzaki S, Batushansky A, Griffin TM, Humphries KM, Olson AL. PFKFB3-dependent glucose metabolism regulates 3T3-L1 adipocyte development. FASEB J 35:e21728, 2021 July, PMID: 34110658, PMCID: PMC8205188
Hettinger ZR, Hamagata K, Confides AL, Lawrence MM, Miller BF, Butterfield TA, Dupont-Versteegden EE. Age-related susceptibility to muscle damage following mechanotherapy in rats recovering from disuse atrophy. J Gerontol A Biol Sci Med Sci, 2021 June, PMID: 34181006
Brown JL, Lawrence MM, Borowik A, Oliver L, Peelor Iii FF, Van Remmen H, Miller BF. Tumor burden negatively impacts protein turnover as a proteostatic process in non-cancerous liver, heart, and muscle, but not brain. J Appl Physiol (1985), 2021 May, PMID: 34013745, PMCID: PMC8325617
Abbott CB, Lawrence MM, Kobak KA, Lopes EBP, Peelor FF 3rd, Donald EJ, Van Remmen H, Griffin TM, Miller BF. A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis. Function (Oxf) 2:zqab028, 2021 May, PMID: 34124684, PMCID: PMC8187230
Wang X, Zhang H, Sapio R, Yang J, Wong J, Zhang X, Guo JY, Pine S, Van Remmen H, Li H, White E, Liu C, Kiledjian M, Pestov DG, Steven Zheng XF. SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer. Nat Commun 12:2259, 2021 April, PMID: 33859191, PMCID: PMC8050259
Yap ZY, Park YH, Wortmann SB, Gunning AC, Ezer S, Lee S, Duraine L, Wilichowski E, Wilson K, Mayr JA, Wagner M, Li H, Kini U, Black ED, Monaghan KG, Lupski JR, Ellard S, Westphal DS, Harel T, Yoon WH. Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes. Genome Med 13:55, 2021 April, PMID: 33845882, PMCID: PMC8042885
Van Pelt DW, Lawrence MM, Miller BF, Butterfield TA, Dupont-Versteegden EE. Massage as a Mechanotherapy for Skeletal Muscle. Exerc Sport Sci Rev 49:107-114, 2021 April, PMID: 33720912, PMCID: PMC8320327
Beckstead MJ, Howell RD. Progressive parkinsonism due to mitochondrial impairment: Lessons from the MitoPark mouse model. Exp Neurol:113707, 2021 March, PMID: 33753138, PMCID: PMC8169575
Wallace MA, Aguirre NW, Marcotte GR, Marshall AG, Baehr LM, Hughes DC, Hamilton KL, Roberts MN, Lopez-Dominguez JA, Miller BF, Ramsey JJ, Baar K. The ketogenic diet preserves skeletal muscle with aging in mice. Aging Cell:e13322, 2021 March, PMID: 33675103, PMCID: PMC8045940
Varshney R, Ranjit R, Chiao YA, Kinter M, Ahn B. Myocardial Hypertrophy and Compensatory Increase in Systolic Function in a Mouse Model of Oxidative Stress. Int J Mol Sci 22, 2021 February, PMID: 33670798, PMCID: PMC7921997
Zhu S, Batushansky A, Jopkiewicz A, Makosa D, Humphries KM, Van Remmen H, Griffin TM. Sirt5 Deficiency Causes Posttranslational Protein Malonylation and Dysregulated Cellular Metabolism in Chondrocytes Under Obesity Conditions. Cartilage:1947603521993209, 2021 February, PMID: 33567897, PMCID: PMC8804736
Jonsson WO, Margolies NS, Mirek ET, Zhang Q, Linden MA, Hill CM, Link C, Bithi N, Zalma B, Levy JL, Pettit AP, Miller JW, Hine C, Morrison CD, Gettys TW, Miller BF, Hamilton KL, Wek RC, Anthony TG. Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex. J Nutr, 2021 January, PMID: 33512502, PMCID: PMC8030708
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Contact Us
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