Physical Therapy & Athletic Training | College of Health
AMPLIFYING MUSCLE AND METABOLIC RECOVERY IN AGING USING METFORMIN AND LEUCINE
Micah Drummond, Associate Professor
Over the next 15 years, there is going to be large number of older people who end up in the hospital. After, many will return home and be less physically active for long periods of time because of slow muscle recovery. The resulting inactive lifestyle decreases muscle size and increases weakness and increases insulin resistance thereby placing older adults at risk for falls, fractures, hospitalizations and development of diabetes. The goal of this project is to re-purpose a common diabetic drug, metformin, and combine it with the essential amino acid, leucine, to improve muscle recovery after the immobilization event. This information will be very important to develop new treatments to prevent muscle atrophy and metabolic decline in older adults.
A unique process that may slow muscle regrowth and delay ample restoration of metabolism during recovery from physical inactivity is increased amounts of muscle inflammation, the build-up of harmful lipid products in muscle, called ceramides, and the reduced health of mitochondria. These events may cause muscle and metabolism to not function properly. Metformin is a very common drug given to those with diabetes. However, evidence in the literature support that metformin when combined with leucine may be able to restore muscle health during recovery from an immobilization event. Therefore, the goal of this project is to test in old mice if metformin in combination with leucine is able to enhance muscle recovery after immobilization.
Communication Sciences & Disorders | College of Health
Effects of acoustic hearing experience on performance of cochlear implant users
Julie Jeon, Assistant Professor
A cochlear implant (CI) was first introduced in the mid-1980s to help post-lingually deafened adults hear again by stimulating auditory nerves directly using electrical stimulation. Since then, outcomes of CIs have improved dramatically which, in turn, extended CI candidacy to young children and people with residual hearing. Today, a child born deaf can receive a CI at around his/her first birthday. There is another group of children who were born with hearing, but became deaf later in life. Etiologies of the late-onset hearing loss may include cytomegalovirus, enlarged vestibular aqueduct, meningitis, genetic factors, etc. These late-onset deaf children can receive CIs later in life.
Previous studies show that CI users perform well with speech perception in quiet but still struggle with speech perception in noise and music appreciation. These difficulties may be due to the limitation of CIs in that they cannot stimulate low-frequency regions well. In this project, we will explore the relationship between voice recognition, speech perception in noise, and music perception in CI users and the CI users’ acoustic hearing experiences before the implantation. We will recruit two CI child groups (early-implanted vs. late-implanted due to late-onset deafness) and compare their voice recognition, speech perception in noise, and music perception abilities. We hypothesize that the late-implanted CI group with longer acoustic hearing experiences will outperform the early-implanted CI group in these measures. This project will help us understand the effect of acoustic hearing experience before implantation on post-operation CI performance.
Nutrition & Integrative Physiology | College of Health
Biological signatures of blueberry-derived microbial metabolites
Anandh Babu Pon Velayutham, Assistant Professor
The research in our laboratory is focused on identifying the molecular mechanisms by which blueberry-derived microbial metabolites improve endothelial dysfunction during metabolic syndrome (MetS). MetS is an important risk factor for cardiovascular mortality and endothelial dysfunction plays a major role in the development of vascular complications. Intact glycocalyx of healthy vasculature acts as a protective barrier and prevents endothelial dysfunction. Glycocalyx, importantly heparan sulfate proteoglycan (HSPG), is severely compromised in MetS. Hence, preservation and restoration of HSPG to improve endothelial dysfunction is a novel strategy to ameliorate vascular complications in MetS.
Human studies support the vascular effects of blueberry anthocyanins. Anthocyanins are extensively metabolized by the gut microbiota in humans, suggesting their vascular benefits might be mediated by their microbial metabolites. Our studies show that: blueberry supplementation improves vascular inflammation and dysfunction, and increases the beneficial bacteria in diabetic mice; and key blueberry metabolites attenuate palmitate or diabetes-induced endothelial inflammation (Mol Nutr Food Res, 2018; Int J Cardiol, 2018). We hypothesize that blueberry attenuates endothelial dysfunction in MetS by improving HSPG and/or acting on multiple targets which is mediated through the microbial metabolites of blueberries. We will use physiologically relevant models, comics approach and state of the art techniques to evaluate the mechanistic roles of metabolites of blueberries. Our study will provide strong scientific rationale for recommending dietary intake of blueberries to improve vascular health in the US population and worldwide.
Nutrition & Integrative Physiology | College of Health
Autophagy and arterial function
J David Symons, Professor
Autophagy (i.e., self-eating) is a cellular process whereby garbage (e.g., damaged proteins) is collected (by the autophagosome), transported to the recycling depot (lysosome), and recycled for future use (e.g., ATP production). Autophagy is critical for maintaining quality control of the cell. Relatively recent evidence indicates that aging compromises the process of autophagy in a number of cell types, damaged proteins accumulate, and cellular dysfunction occurs. While aging too is associated with a progressive decline in arterial function, the mechanisms are unclear, and a direct link with vascular autophagy has not been tested. What is meant by arterial dysfunction?
Arterial dysfunction is, in part, a limitation of the ability of endothelial cells to synthesize and release nitric oxide (NO), but the mechanisms are unclear. We plan to determine whether limited endothelial cell autophagy contributes to repressed endothelial cell NO production, and subsequent vascular dysfunction, during the process of aging. How can the specific contribution from EC autophagy be tested?
The process of autophagy requires autophagy-related genes (Atg’s). One of these genes is Atg3. After determining that indices of endothelial cell autophagy (e.g., Atg3) decline in old vs. adult mice, we showed that repressed endothelial cell autophagy per se contributes to impaired endothelial cell NO generation using endothelial cell specific “knockout” mice, and we elucidated the mechanisms responsible. The 2018 SPUR student will help to determine whether the aging-associated decline in arterial autophagy contributes directly to the aging associated decline in arterial function.