Pilot Studies
Researchers from the University of Florida are investigating a variety of specialized topics relating to aging and mobility. Each pilot study is funded and lasts for one to two years. Click the link on each study card to learn more about the project.
Muscle aging
mRNA translation reprograming across muscle aging and mobility loss
Age-related muscle loss stems from a breakdown in protein homeostasis, but how mRNA translation fidelity (the accuracy of making proteins) changes with aging remains unknown. Utilizing a novel transgenic mouse model and our discovery of specialized, heterogeneous ribosomes in muscle, this project will investigate how translation fidelity declines across the lifespan and how aging alters ribosome composition. Finally, we will test whether voluntary exercise combats muscle aging by actively restoring and optimizing this translation fidelity.
mobility loss
Impacts of AB-free Kava on Mitigating Mobility Loss with Aging: A Pilot Study
This pilot study evaluates AB-free kava—a safe, hepatotoxin-free formulation—as a multimodal intervention to combat age-related mobility loss by simultaneously targeting poor sleep, chronic stress, and systemic inflammation. The study will primarily assess trial feasibility, safety, and adherence, while additionally tracking improvements in mobility, sleep quality, and underlying biomolecular markers to justify a future full-scale trial.
Pilot Study Abstracts
Read more details below about the pilot studies listed above.
mRNA translation reprograming across muscle aging and mobility loss
Principal Investigator: Fujii Kotaro, PhD
The loss of muscle mass and mobility leads to disability, poor quality of life, and death. Skeletal muscle mass decline across the aging process is associated with a gradual decline in the ability of the muscle cells to maintain protein homeostasis, which is characterized by an imbalance between protein synthesis and degradation. While significant research has explored the age-dependent decline in protein folding and degradation, research into protein synthesis is scant. Particularly, since mRNA translation is the most error-prone step of gene expression and error-containing proteins are prone to be unfolded and aggregated, increasing translation errors and declining the fidelity of mRNA translation must provide a significant impact on protein homeostasis. However, how the translation fidelity changes across the aging process and the role of translation fidelity on protein homeostasis and aging are still largely unknown, due to two key reasons: 1) the lack of an in vivo model to assess translation fidelity in organisms, and 2) the assumption that translation fidelity is just kinetics based on the translation activity rather than controlled or optimized for each specific biological context. Our recent progress made a huge breakthrough by developing a novel transgenic (Tg) mouse model monitoring translation fidelity by a dual-luciferase gain-of-activity reporter. Excitingly, our results showed organ-specific error rates in young adult mice, indicating that each organ develops unique translation fidelity programs to ensure the functional proteomes for each organ. Since the loss of protein homeostasis is a primary hallmark of aging, we hypothesize that fidelity will decrease across the lifespan. To address this question, we will explore how translation fidelity evolves throughout aging in Aim 1. Historically, all ribosomes have been thought to have the same components. Our previous finding demonstrated ribosome heterogeneity in the components and function for mRNA translation. Such heterogeneous ribosomes have been identified in muscles with crucial functions to control muscle mass. Therefore, we hypothesized that such heterogeneous ribosomes are affected by aging. Furthermore, since our Tg mice revealed high translation fidelity in young adult muscle, we thought such specialized ribosomes in muscle were involved in fidelity regulation. To test these hypotheses, we will purify actively translating ribosomes from aged mice to monitor the ribosome composition in Aim 2. Exercise is a well-established intervention for promoting healthy aging and preserving mobility, yet the molecular mechanisms underlying its protective effects remain incompletely understood. Exercise has been shown to increase muscle mass through the regulation of heterogeneous ribosomes. Regular exercise has also been shown to reduce the basal activity of mTOR, a master regulator of translation activity and fidelity. Therefore, we thought fidelity and translation control could be a primary source of the systemic, beneficial effects from exercise. To test this hypothesis, we will monitor translation fidelity after voluntary wheels running activity for two weeks in young adult (6 months), middle-aged (18 months), and geriatric (24 months) mice in Aim 3.
Impacts of AB-free Kava on Mitigating Mobility Loss with Aging: A Pilot Study
Principal Investigator: Xing Chengguo, PhD
Mobility maintenance is key to healthy aging. A wide range of factors contribute to mobility loss with aging, including compromised sleep, chronic stress, depression, sedentary lifestyle, and systemic
inflammation; many of these factors communicate and interact with each other, and may contribute differentially among individuals to their mobility loss, reflecting the multi-complexity of mobility loss with aging. Effective interventions likely need to be multimodal that ideally address several etiological factors simultaneously, such as AB-free kava. Kava traditionally is a beverage among South Pacific Islanders that improves sleep and reduces stress. It is also marketed as a “calming” dietary supplement in the U.S.A. It was once used to treat anxiety in Europe until purported rare but severe hepatotoxicity in the late 1990s, likely due to the ill-use of poor-quality raw materials containing high levels of hepatotoxic ingredients (flavokavains A & B) from cultivars not recommended for human use, leading to its ban in Europe. The World Health Organization and many others have reviewed the evidence and concluded that kava is safe for human consumption with proper preparations. A kava formula mimicking the traditional preparation with the hepatoxic ingredients removed was developed (named AB-free kava). Our earlier pilot single-arm one-week trial among smokers (N=21) revealed its potential in sleep improvement, stress reduction, and systemic inflammation amelioration. A recent cross-over 2-week AB-free kava trial from our collaborators discovered its potential to enhance motivation to exercise among young males during intensive training. Our pre-clinical data also showed that AB-free kava increased travel distance in adult mice. These data cohesively support the potential of AB-free kava in improving mobility and physical functions. Our pilot clinical and pre-clinical data, as well as existing literature, suggest that AB-free kava modulates β-adrenergic receptor medicated protein kinase A (PKA) signaling as the underly mechanism. We thus hypothesize that AB-free kava safely and effectively improves mobility and physical functions among older adults through sleep improvement and stress reduction via modulating PKA signaling. Leveraging the outstanding clinical research infrastructure and expertise in the University of Florida Claude D. Pepper Older Americans Independence Center (OAIAC), we will perform a pilot study to test our hypothesis, utilizing a double blind randomized placebo-controlled design with an 8-week AB-free kava intervention in older adults (age ≥ 70 years, n = 15/arm) at risk for functional decline due to poorer sleep. Our primary endpoint is trial feasibility, including successful enrollment, high adherence retention, and safety of AB-free kava among older adults. We will also assess the effects of AB-free kava on mobility and physical functions in addition to sleep, chronic stress and associated systemic inflammation and PKA signaling. If the results support our hypothesis, we will be well positioned to carry out a rigorously powered, randomized controlled trial (RCT) with well-defined primary endpoints related to mobility with aging in at-risk older adults.