Holly Van Remmen, Ph.D.

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.

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.

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.

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

Joined OMRF’s Scientific Staff in 2013

Recent Publications

Deepa SS, Pharaoh G, Kinter M, Diaz V, Fok WC, Riddle K, Pulliam D, Hill S, Fischer KE, Soto V, Georgescu C, Wren JD, Viscomi C, Richardson A, Van Remmen H. Lifelong reduction in complex IV induces tissue-specific metabolic effects but does not reduce lifespan or healthspan in mice. Aging Cell. 2018 Apr 25:e12769. Epub ahead of print. PMID: 29696791

Ahn B, Pharaoh G, Premkumar P, Huseman K, Ranjit R, Kinter M, Szweda L, Kiss T, Fulop G, Tarantini S, Csiszar A, Ungvari Z, Van Remmen H. Nrf2 deficiency exacerbates age-related contractile dysfunction and loss of skeletal muscle mass. Redox Biol. 2018 Apr 6; 17:47-58. Epub ahead of print. PMID: 29673700

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 Mar; 9:141-155. PMID: 29398615

Selected Publications

Masser DR, Clark NW, Van Remmen H, Freeman WM. Loss of the antioxidant enzyme CuZnSOD (Sod1) mimics an age-related increase in absolute mitochondrial DNA copy number in the skeletal muscle. Age (Dordr). 2016 Aug;38(4):323-33. PMCID:PMC5061674

Alund AW, Mercer KE, Suva LJ, Pulliam CF, Chen JR, Badger TM, Van Remmen H, Ronis MJ. Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice. J Pharmacol Exp Ther. 2016 Jul;358(1):50-60. PMCID:PMC4931876

Pharaoh G, Pulliam D, Hill S, Sataranatarajan K, Van Remmen H. Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPR(MT) and increased resistance to oxidative stress in primary cultures of fibroblasts. Redox Biol. 2016 Aug;8:430-8. PMCID:PMC4878459

Walsh ME, Bhattacharya A, Sataranatarajan K, Qaisar R, Sloane L, Rahman MM, Kinter M, Van Remmen H. The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging. Aging Cell. 2015 Dec;14(6):957-70.  PMCID:PMC4693467

Evans TM, Jaramillo CA, Sataranatarajan K, Watts L, Sabia M, Qi W, Van Remmen H. The effect of mild traumatic brain injury on peripheral nervous system pathology in wild-type mice and the G93A mutant mouse model of motor neuron disease. Neuroscience. 2015 Jul 9;298:410-23. PMCID:PMC4470701

Evans TM, Van Remmen H, Purkar A, Mahesula S, Gelfond JA, Sabia M, Qi W, Lin AL, Jaramillo CA, Haskins WE. Microwave & Magnetic (M2) proteomics of a mouse model of mild traumatic brain injury. Transl Proteom. 2014 Jun 1;3:10-21. PMCID:PMC4492171

View all publications in PubMed

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

Shylesh Bhaskaran, Ph.D.
Associate Staff Scientist

Kavithalakshmi Satara Natarajan, Ph.D.
Associate Staff Scientist

Bumsoo Ahn, Ph.D.
Postdoctoral Fellow

Jacob Brown, Ph.D.
Postdoctoral Fellow

Rizwan Qaisar, Ph.D.
Postdoctoral Fellow

Ashwini Poopal
Senior Research Assistant

Pavithra Premkumar
Research Assistant

Ashley Murphy
Senior Research Technician

Kaitlyn Riddle
Senior Research Technician

Jan Bian
Research Technician

Rojina Ranjit
Research Technician

Shauna Hill
Graduate Student

Gavin Pharoah
Graduate Student

Jeannie Evans
Project Coordinator II