Benjamin Miller, PhD

Biography

Benjamin Miller, PhD is a Member (Full Professor equivalent) in the Aging and Metabolism Program at the Oklahoma Medical Research Foundation (OMRF). Dr. Miller is an Adjunct Professor of Biochemistry and Molecular Biology at University of Oklahoma Health Sciences Center, a core leader in the NIA-sponsored Nathan Shock Center, and Director of Translational Science for the Oklahoma Center for Geroscience.

Dr. Miller studies the interaction of mitochondrial energetics, protein turnover, and stress resistance with aging. His primary interest is age-related loss of muscle function, but his work spans multiple tissues. Dr. Miller’s work translates the basic biology of aging through clinical interventions, which often include exercise. Dr. Miller’s most notable contributions and recognition have come from his work with stable isotopes to study protein turnover and metabolic flux. Through this work, he has developed several new approaches to understand turnover. Besides his own research, he has leant his expertise with stable isotopes to many other investigators, especially junior PIs. Dr. Miller has authored over 115 articles, has continuous NIH funding, has served on multiple NIH study sections, and has several leadership positions through his professional affiliations.

Email

Benjamin-miller@omrf.org

Additional Websites

• Publications
• Miller Lab (OMRF)

Research Interests:

• Maintaining proteostasis with aging: The Geroscience Initiative identified proteostasis as one of the seven “pillars” of aging research. Proteostasis refers to the processes that maintain proteome fidelity. My research focuses on the biosynthesis and turnover components of proteostasis. In this regard, we make direct measures of these dynamic processes, not markers or indicators, which has led to important insight into shared characteristics of slowed aging. By using stable isotopes to simultaneously measure both protein synthesis and DNA synthesis in vitro and in vivo we have made two discoveries: 1) mitochondrial proteins are selectively translated in slowed aging models, and 2) when accounting for cell proliferation, the turnover of proteins in existing cells is increased, not decreased. These findings are repeatable in several slowed aging models and slowed aging treatments.
• Stress resistance and slowed aging: Like proteostasis, The Geroscience Initiative identified stress resistance as a “pillar” of aging research. My interest in stress resistance spurred from our work with the transcription factor Nrf2. From this work, we proposed a Nrf2 activator to the NIA Interventions Testing Program (ITP), which increased median lifespan in male mice. We followed this up with the proposal of a second-generation Nrf2 activator, which is currently in testing. We have used these Nrf2 activators both as a means to understand the aging process as well as treat it.
• Translation of treatments to slow aging: It is my goal to translate our more basic science into potential human treatments to slow aging. We do this using unique animal models and with clinical trials in humans. My work in humans has focused either on exercise, metformin, or Nrf2 activation. More specifically, we have investigated the efficacy of these treatments to slow age-related declines in skeletal muscle mitochondrial function and skeletal muscle mass. For example, some in the aging field are pushing metformin to be the first drug used to treat aging. We have data both in support and against such use. It is clear to us that the field needs more evidence before pushing such an expensive clinical trial.
• Approaches: Stable isotopes and mass spec are key features of my research program. In this regard, I consider our lab a leader in the use of D2O to measure in vitro and in vivo biosynthetic processes. We are working on methods to expand these approaches in order to continue to improve measurements of kinetic processes. I also have extensive experience in using stable isotopes for the assessment of metabolic flux. In combination these approaches allow us to explore the interface between protein and energetics.