Holly Van Remmen, Ph.D.
Member and Program Chair
Aging & Metabolism Research Program
G.T. Blankenship Chair in Aging Research
My 101
In the year 1900, the average U.S. lifespan was 46 years for men and 48 years for women. In 2013, the average was 76 for men and 81 for women. Advances in medical science and human health have people living longer, but new challenges arise with an extended lifespan.
Research in my lab focuses on aging. One question we’re keen to answer is: Why do people lose muscle as they get older? It’s a normal part of aging, but it bears similarity to a disease called sarcopenia, in which the body loses skeletal muscle mass. Using a mouse model of sarcopenia, we’re looking specifically at the role of oxidative stress, or free radicals, in the long-term deterioration of muscle. As part of this research, we are studying how mitochondria are affected by aging and might contribute to aging. Mitochondria are present in all cells and are responsible for generating energy and controlling metabolism and also for producing the majority of oxidative stress as a by-product of their function.
Another disease in which oxidative stress affects muscles is amyotrophic lateral sclerosis, often called ALS or Lou Gehrig’s disease. In ALS, a group of cells called motor neurons is affected, reducing a patient’s ability to control their muscles. We also use a mouse model of ALS to study how the loss of an enzyme affects motor neurons.
Importantly , we are now testing potential interventions to reduce or delay loss of muscle and weakness in aging and motor neuron degeneration in aging and ALS. We hope to move some of our findings to the clinic in the future. Our goal is not to find a “fountain of youth,” but to address the declining quality of life as we age. It’s important that our “healthspan” matches our lifespan.
Research
My research program has focused on the role of oxidative stress and mitochondrial function in aging. We utilized a number of transgenic and knockout models with modified antioxidant defense systems to ask whether changes in antioxidant defense and oxidative stress modify lifespan as predicted by the long-standing Oxidative Stress Theory of Aging. In contrast to the predictions of this Theory, our studies have shown that modifying antioxidant defenses does not alter lifespan. These studies suggest that oxidative stress may not be a primary factor underlying aging per se. However, we propose the oxidative stress is indeed a critical factor in age-associated diseases such as sarcopenia and Amyotrophic Lateral Sclerosis (ALS). Our recent work has focused on the role of mitochondria and oxidative stress on alterations in the motor neurons, the neuromuscular junction and skeletal muscle that might contribute to the significant problem of age-related loss of muscle mass and may have implications for onset and progression of ALS. In another line of research, we are studying the role of the mitochondrial unfolded protein response (mtUPR) in aging and the potential for tissue cross-talk based on mitochondrial signaling that might influence changes in metabolism. As part of these studies, we are interested in studying age related changes in components of the mtUPR such as heat shock proteins and mitochondrial proteases Lon and ClpP.
Brief CV
Education
B.S. Eastern Illinois University, Charleston, IL, 1983
Ph.D. University of Texas Health Science Center, San Antonio, TX, 1991
Postdoc UTHSC, San Antonio, TX, with Arlan Richardson, Ph.D., 1991-1995
Honors and Awards
1988 - Proctor and Gamble Professional Opportunity Award, American Physiologic Society
1990 - Graduate Studies in Physiology Award for Excellence, Graduate School of Biomedical Sciences, University of Texas Health Science Center at San Antonio
1991 - Sacher Graduate Student Award, Biological Sciences, Gerontological Society of America
1992 - Geriatric Leadership Academic Award, Aging Research and Education Center, University of Texas Health Science Center at San Antonio
1994 - Geriatric Leadership Academic Award, Aging Research and Education Center, University of Texas Health Science Center at San Antonio
1995 - American Federation for Aging Research Award
2007 - Dielmann Distinguished Endowed Chair in Aging
2010 - Ellison Medical Foundation Senior Scholar
Memberships
1984-present - American Physiological Society
1997-present - Oxygen Society/Society for Free Radical Biology in Medicine
1999-2009 - San Antonio Cancer Institute
2000-present - American Aging Association, Member/Board Member, President-Elect (2022-27)
Joined OMRF’s Scientific Staff in 2013
Publications
Recent Publications
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
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
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
Selected Publications
Muscle Mitochondrial Catalase Expression Prevents NMJ Disruption, Atrophy and Weakness in a Mouse Model of Accelerated Sarcopenia. Hongyang Xu, Rojina Ranjit, Arlan Richardson and H. Van Remmen. J Cachexia Sarcopenia Muscle. Accepted.
Piekarz KM, Bhaskaran S, Sataranatarajan K, Street K, Premkumar P, Saunders D, Zalles M, Gulej R, Khademi S, Laurin J, Peelor R, Miller BF, Towner R, Van Remmen H. Molecular changes associated with spinal cord aging. Geroscience. 2020 Apr;42(2):765-784. doi: 10.1007/s11357-020-00172-6. Epub 2020 Mar 6.PMID: 32144690, PMCID: PMC7205981
Pharaoh G, Brown JL, Sataranatarajan K, Kneis P, Bian J, Ranjit R, Hadad N, Georgescu C, Rabinovitch P, Ran Q, Wren JD, Freeman W, Kinter M, Richardson A, Van Remmen H. Targeting cPLA2 derived lipid hydroperoxides as a potential intervention for sarcopenia. Scientific Reports. 2020 Aug 18;10(1):13968. doi: 10.1038/s41598-020-70792-7.PMID: 32811851, PMCID: PMC7435184
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, Brook SV, Van Remmen H. Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fiber branching. J Cachexia Sarcopenia Muscle. 10:411-428, 2019. PMID: 30706998, PMCID: PMC6463475
Bhaskaran S, Pollock N, C Macpherson P, Ahn B, Piekarz KM, Staunton CA, Brown JL, Qaisar R, Vasilaki A, Richardson A, McArdle A, Jackson MJ, Brooks SV, Van Remmen H. Neuron-specific deletion of CuZnSOD leads to an advanced sarcopenic phenotype in older mice. Aging Cell. 2020 Sep 4:e13225. doi: 10.1111/acel.13225. Online ahead of print. PMID: 32886862, PMCID: PMC7576239
Jang, Y.C., Liu, Y., Hayworth, C.R., Bhattacharya, A., Lustgarten, M.S., Muller, F.L., Chaudhuri, A., Qi, W., Li, Y., Huang, J.Y., Verdin, E., Richardson, A. and Van Remmen, H. Dietary restriction attenuates age- associated muscle atrophy by lowering oxidative stress in mice even in complete absence of CuZnSOD. Aging Cell 11:770-82 2012. PMID: 22672615, PMCID: PMC3444532
Contact
Aging & Metabolism Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-2520
Fax: (405) 271-3470
E-mail: holly-vanremmen@omrf.org
For media inquiries, please contact OMRF’s Office of Public Affairs at news@omrf.org.
Lab Staff
Jacob Brown, Ph.D.
Research Assistant Member
Shylesh Bhaskaran, Ph.D.
Staff Scientist
Kavitha Lakshmi Satara Natarajan, Ph.D.
Staff Scientist
Hongyang "Yang" Xu, Ph.D.
Post-Doctoral Fellow
Jessica Thomason
Research Technician II
Hannah Hagy
Research Technician
Ashley Murphy
Senior Laboratory Technician
Tamy Aguero Fraire
Laboratory Assistant
Jeannie Evans
Project Coordinator II
Tracy Cardinal
Administrative Assistant III
Holly Smith
Administrative Assistant III
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