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.

2018

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. 2018 Feb 2:e45009. PMID:29420235

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. 2018 Oct;9(5):987-1002.  PMID:30328290

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. 2017 Dec 20. PMID: 29272412

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. 2018 Aug 31;11(9). pii: dmm034827.  PMID:30018076

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. 2018 Oct 23;8(1):1533754.   PMID:30370017

Hill S, Sataranatarajan K, Remmen HV.  Role of Signaling Molecules in Mitochondrial Stress Response.  Front Genet. 2018 Jul 10;9:225.  PMID:30042784

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. 2018 Dec 11:e12880. PMID:30548390

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. 2018 Nov 27;9(1):5008.  PMID:30479337

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. 2018 Feb 1:S2212-8778(17)30929-8.  PMID:29398615

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. 2018 Dec;33(12):1928-37. PMID:30440089

Plafker KS, Zyla K, Berry W, Plafker SM.  Loss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence.  Redox Biol. 2018 May 21;17:411-22.  PMID:29879550

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. 2018 Oct;9(5):100317.   PMID:30073804

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. 2018 Sep 27;20:68-74.  PMID:30296699

Ryan T, Bamm VV, Stykel MG, Coackley CL, Humphries KM, Jamieson-Williams R, Ambasudhan R, Mosser DD, Lipton SA, Harauz G, Ryan SD. Cardiolipin exposure on the outer mitochondrial membrane modulates α-synuclein. Nat Commun. 2018 Feb 26;9(1):817.  PMCID: PMC5827019

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. 2018 Jun 14;73(7):853-63. PMID:29905772

Tschumi CW, Beckstead MJ.  Diverse actions of the modulatory peptide neurotensin on central synaptic transmission.  Eur J Neurosci. 2018 Feb 6.  PMID: 29405480

Tschumi CW, Beckstead MJ. Neurotensin speeds inhibition of dopamine neurons through temporal modulation of GABA(A) and GABA(B) receptor-mediated synaptic input. Neuropharmacology. 2018 Mar 15;131:414-23. PMID: 29307543

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. 2018 Apr 25. pii: S1931-5244(18)30070-7.  PMID:29758174

2017

*Barboza E, Hudson J, Chang WP, Kovats S, Towner RA, Silasi-Mansat R, Lupu F, Kent C, Griffin TM. Pro-fibrotic infrapatellar fat pad remodeling without M1-macrophage polarization precedes knee osteoarthritis in diet-induced obese mice. Arthritis Rheumatol. 2017 Jun;69(6):1221-1232. PMCID: PMC5449220

Bastian A, Matsuzaki S, Humphries KM, Pharaoh GA, Doshi A, Zaware N, Gangjee A, Ihnat MA. AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization. Cancer Lett. 2017 Mar 1;388:149-157. PMCID: PMC5318233

Bhaskaran S, Unnikrishnan A, Ranjit R, Qaisar R, Pharaoh G, Matyi S, Kinter M, Deepa SS. A fish oil diet induces mitochondrial uncoupling and mitochondrial unfolded protein response in epididymal white adipose tissue of mice. Free Radic Biol Med. 2017 Apr 26;108:704-14.  Epub ahead of print.  PMID: 28455142

Chen M, Nowak DG, Narula N, Robinson B, Watrud K, Ambrico A, Herzka TM, Zeeman ME, Minderer M, Zheng W, Ebbesen SH, Plafker KS, Stahlhut C, Wang VM, Wills L, Nasar A, Castillo-Martin M, Cordon-Cardo C, Wilkinson JE, Powers S, Sordella R, Altorki NK, Mittal V, Stiles BM, Plafker SM, Trotman LC. The nuclear transport receptor Importin-11 is a tumor suppressor that maintains PTEN protein. J Cell Biol. 2017 Mar 6;216(3):641-56. Epub 2017 Feb 13. PMCID: PMC5350510

Deepa SS, Bhaskaran S, Espinoza S, Brooks SV, McArdle A, Jackson MJ, Van Remmen H, Richardson A. A new mouse model of frailty: the Cu/Zn superoxide dismutase knockout mouse. Geroscience. 2017 Apr;39(2):187-198.  PMCID: PMC5411367

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. 2017 Dec 20. PMID:29272412

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. 2017 Nov 27. pii: e201707966. PMID:29180355

Hill S, Deepa SS, Sataranatarajan K, Premkumar P, Pulliam D, Liu Y, Soto VY, Fischer KE, Van Remmen H. Sco2 deficient mice develop increased adiposity and insulin resistance. Mol Cell Endocrinol. 2017 Apr 18. pii: S0303-7207(17)30190-9. Epub ahead of print.  PMID: 28428045

Kalaitzoglou E, Griffin TM, Humphrey MB. Innate Immune Responses and Osteoarthritis. Curr Rheumatol Rep. 2017 Aug;19(8):45. Review.  PMID: 28718060

Pardo G, Jones DE.  Correction to: The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations. J Neurol. 2017 Dec;264(12):2375-7. PMID:29063239 

Pearsall EA, Cheng R, Zhou K, Takahashi Y, Matlock HG, Vadvalkar SS, Shin Y, Fredrick TW, Gantner ML, Meng S, Fu Z, Gong Y, Kinter M, Humphries KM, Szweda LI, Smith LEH, Ma JX. PPARα is essential for retinal lipid metabolism and neuronal survival. BMC Biol. 2017 Nov 28;15(1):113. PMCID:PMC5706156 

Sakellariou G, McDonagh B, Porter H, Giakoumaki I, Earl K, Nye G, Vasilaki A, Brooks S, 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. 2017 Oct 25. PMID:29065712

*Sandoval IT, Delacruz RG, Miller BN, Hill S, Olson KA, Gabriel AE, Boyd K, Satterfield C, Remmen HV, Rutter J, Jones DA. A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC). Elife. 2017 Apr 11;6. pii: e22706.  PMCID: PMC5388534

Vadvalkar SS, Matsuzaki S, Eyster CA, Giorgione JR, Bockus LB, Kinter CS, Kinter M, Humphries KM. Decreased Mitochondrial Pyruvate Transport Activity in the Diabetic Heart: role of mitrochondrial pyruvate carrier 2  (MPC2) acetylation. J Biol Chem. 2017 Mar 17;292(11):4423-33.  PMCID: PMC537776

Walsh ME, Van Remmen H. Emerging roles for histone deacetylases in age-related muscle atrophy. Nutr Healthy Aging. 2016 Oct 27;4(1):17-30.  Review.   PMCID: PMC5166515

Zhang N, Valentine JM, Zhou Y, Li ME, Zhang Y, Bhattacharya A, Walsh ME, Fischer KE, Austad SN, Osmulski P, Gaczynska M, Shoelson SE, Van Remmen H, Chen HI, Chen Y, Liang H, Musi N. Sustained NFκB inhibition improves insulin sensitivity but is detrimental to muscle health. Aging Cell. 2017 May 29.   PMID: 28556540

* Indicates publications by more than one department or program.

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