Active Awards

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.

Pilot Study Abstracts

Read more details below about the pilot studies listed above.


Cora Best

Effects of a Ketogenic Diet Versus Mediterranean Diet on Markers of Bone Health and Muscle Function in Older Adults

Principal Investigator: Cora Best, PhD

Age-related conditions include osteoporosis and sarcopenia, which often co-occur and significantly increase the risk for fractures. Fragility fractures result in staggering economic costs to the U.S. and severely limit the independence of older Americans. Diet is a powerful tool to combat age-related conditions. Preclinical and emerging clinical data indicate that a very low carbohydrate ketogenic diet (KD) may help prevent progression of age-related conditions like neurodegenerative diseases, certain cancers, and sarcopenia. However, it may exacerbate bone loss in older adults. A better understanding of the physiologic effects of KD on the musculoskeletal system of older adults is needed to inform the benefit-risk assessment for an older patient and optimize the effectiveness of KD for age-related conditions.

The most clinically relevant comparator for KD is another therapeutic diet for which there is evidence of benefit for age-related conditions: the Mediterranean diet (MD). We will pilot test a randomized clinical trial comparing the effects of a well-formulated KD and MD on body composition and clinically relevant markers of bone health and muscle function in older adults. We will evaluate the feasibility of our trial (aim 1) and obtain the data necessary to justify and improve the scientific rigor of a future clinical trial (aim 2). The long-term goals of this research are to determine the relative effects of a KD compared with MD on indicators of musculoskeletal health in older adults. That knowledge is required to guide clinical nutrition care. Support for the proposed research will be an important investment in the research program of an early-career investigator with a strong record of scientific accomplishment.

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Arianna Brice-Tutt

Cannabidiol and Oxycodone Interactions on Pain and Mobility in Aged Rats

Principal Investigator: Arianna Brice-Tutt, PhD

Older adults are at increased risk for developing chronic pain. This, coupled with functional declines in mobility, has a significant detrimental impact on quality of life. Opioids are often prescribed for treating chronic pain; however, their use is hindered by undesired side effects. Older adults on prescription opioids for treating chronic pain are at greater risk of fall-related fractures and opioid-related hospitalizations. Further, while older adults often report subjective improvements in their pain from opioids, they report little improvements in their day-to-day function and mobility. Thus, there is a great need for safer, effective treatments for chronic pain that improve mobility and quality of life for elderly patients with chronic pain.

Of particular interest, cannabidiol, a major constituent of cannabis, has gained considerable popularity in the general public for treating various conditions such as anxiety, depression, and chronic pain. Notably, cannabidiol lacks major psychotropic and rewarding properties and is considered safe and well tolerated. Thus, cannabidiol may be particularly beneficial as a therapeutic for elderly patients, as they often have increased adverse outcomes from prescription and over-the-counter pain-relievers. Moreover, cannabidiol has anti-inflammatory and antioxidant properties, which are heavily implicated in aging and chronic pain. We and others find cannabidiol appears to have opioid-sparing properties specific to analgesic activity. Together, this suggests cannabidiol has therapeutic potential to treat chronic pain alone, or by improving the therapeutic window of opioids. Therefore, this proposal will investigate the benefit of cannabidiol, alone and in combination with oxycodone, to alleviate chronic pain and improve mobility in young and aged rats. We will also investigate effects on related biomarkers of inflammation and oxidative stress. The ultimate goal is to improve understanding of the therapeutic and mechanistic effects of cannabidiol which will bring us closer to better and safer treatments for mobility and chronic pain in elderly patients.

Chronic pain affects nearly 1 in 4 Americans, making it one of the most common and costly diseases in the United States. In the U.S. alone, annual costs related to chronic pain exceed 600 billion. The majority of chronic pain patients are individuals over the age of 65. Indeed, aging is a risk factor for chronic pain, and often the primary cause of disability or consequent to other diseases in older adults5. In the elderly, chronic pain worsens existing issues, such as psychiatric conditions, cognitive deficits, functional decline in mobility, and social isolation. All of these are detrimental to quality of life. Further complicating matters, safe and effective treatment of chronic pain in older adults is challenging, as they often have comorbid conditions and age-related pharmacokinetic and pharmacodynamic changes. Accordingly, older adults on prescription opioids for treating chronic pain are at greater risk of fall-related fractures and brain injuries and opioid-related hospitalizations. Further, while older adults often report subjective improvements in pain from opioid therapy, they report little improvement in their day-to-day function and mobility. Thus, there is a great need for safer, more effective treatments for chronic pain that improve mobility and quality of life for elderly patients. Of particular interest, cannabinoid cannabidiol (CBD) is suggested to be effective against chronic pain and reduces age and pain-related biomarkers. CBD has gained considerable popularity in the general public for treating conditions such as anxiety, depression, and pain. Unlike other cannabinoids, CBD is not psychoactive and is considered safe and well tolerated in humans, making it an ideal candidate for use in older adults.

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Yan Wang

Investigating Neighborhood Mobility Resilience and Aging

Principal Investigator: Yan Wang, PhD

Extreme weather and climate events (EWCE) such as hurricanes are expected to increase in both frequency and intensity due to anthropogenic-induced warming; in the meantime, population aging continues to lead to the emergence of highly vulnerable coastal communities and manifest climate change risks over the long term. While some previous research has noted that older adults are more vulnerable to adverse health outcomes due to EWCE, there is limited knowledge about their impact on gerontological outcomes such as life-space mobility (LSM) and mobility resilience (MR). LSM, defined as the distance and amount of time spent away from home, is a strong predictor of physical disability, cognitive impairment and overall quality of life. The extant quantitative studies on LSM and MR have predominantly focused on small-samples (n<100) in a static manner – only assessed over a short period of time. As such, this work is unable to track older adults’ MR under EWCE over a long time across neighborhoods. It is thus imperative to understand, quantify, and explain older adults’ MR to EWCE to inform resilient aging (our long-term goal).

The proposed pilot project will test a central hypothesis that neighborhood aging vulnerability (characterized by age structure and ratio of older adults with limitations) is associated with neighborhood MR (measured based on a resilience triangle built upon dynamics of neighborhood mobility index), and the link is moderated by neighborhood socioeconomic status. We leverage a new data resource – large-quantity mobile device-based Points of Interest Visits data – to examine neighborhood-based aggregated LSM and quantify MR to the EWCE. We center on 4,749 exposed neighborhoods (i.e. census tracts) within Florida, residing a population of 4,176,428 older adults aged 65 and over, who were impacted by Hurricane Ian in 2022. We will first measure neighborhood MR to EWCE using the Resilience Triangle. Using this new data resource, we will develop a Neighborhood Mobility Index and track the dynamic values before, during, and after the hurricane to retrieve the curves of the Resilience Triangle, which serve as the basis to suggest different levels of neighborhood MR.

We will further determine if neighborhood aging vulnerability is associated with neighborhood MR and if the relation is moderated by socioeconomic status. To our knowledge, this will be the first empirical study to converge the conceptualization and quantification of MR in both health and non-health disciplines through the framework of the Resilience Triangle. Through the pilot project, we will be among the first to employ the new data resource, explore novel metrics for measuring neighborhood-based LSM and resilience, and generate new knowledge for neighborhood-level aging vulnerability and its association with MR. Research outcomes can inform geographically mobility-vulnerable neighborhoods under EWCE for more targeted interventions across healthcare and built environment domains.

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Javier Tamargo

Krill Oil for Pain and Physical Function in Older Adults

 Principal Investigator: Javier Tamargo, PhD

Mobility is a critical factor in the maintenance of independence and quality of life of older adults. Chronic musculoskeletal pain contributes to mobility disability disproportionately among older adults. Current treatments for pain and functional decline are often ineffective and add to heightened risks of polypharmacy in older adults. As such, nutritional interventions can play a significant role in promoting health and longevity, managing pain, and enhancing physical function in older adults. Omega (ω)-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that are well recognized for their anti-inflammatory and cardioprotective benefits, as well as their analgesic and anti-nociceptive properties. Most American adults do not meet the recommendations for ω-3 intakes, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found primarily in seafood. Due to competing pathways, an elevated ω-6 to ω-3 ratio contributes to an overproduction of pro-inflammatory eicosanoids and the development of chronic diseases. A high ω-6:ω-3 ratio is associated with higher chronic pain prevalence and increased pain severity. Additionally, ω-3 PUFAs may play a role in the preservation of muscle and physical function in older adults. Low levels of ω-3s in blood are associated with reduced muscle strength, slower gait speed, and mobility disability among older adults.

Considered largely safe and cost-effective, ω-3 supplementation may be crucial to increasing the intake of these essential nutrients and achieving optimal levels among older adults. Although the use of EPA and DHA has been incorporated into several guidelines, a scarcity of data has prevented the development of strong recommendations on the use of ω-3 supplementation for the maintenance of physical function in older adults, particularly those with chronic musculoskeletal pain. Krill oil has been recently proposed as an advantageous alternative to traditional fish oil supplements, due to a greater bioavailability of EPA and DHA and additional bioactive compounds.

The goal of the proposed pilot study is to assess the feasibility of a 3-month randomized controlled trial to determine the effectiveness of krill oil supplementation on pain and physical function in older adults with chronic musculoskeletal pain. We will enroll 40 older adults (≥60 years) who will be randomly assigned to 4 g krill oil (1,288 mg/d EPA+DHA, 0.45 mg astaxanthin, 320 mg choline) daily or matched placebo (mixed lipids without EPA and DHA). We will determine the impact of krill oil supplementation on the omega-3 index (%EPA+DHA in erythrocytes), the ω-6/ω-3 ratio, and inflammatory biomarkers in blood, and obtain preliminary evidence of its impact on pain and physical function in older adults. The findings of this pilot will inform a future fully-powered randomized controlled trial by assessing the feasibility and acceptability of krill oil supplementation among older U.S. adults with chronic musculoskeletal pain.

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Russell Hepple

Mechanisms Linking Brain and Skeletal Muscle Aging

 Principal Investigator: Russell Hepple, PhD

The primary objectives of this study are to evaluate two novel hypotheses concerning potential mechanisms that link brain and skeletal muscle aging. In Aim 1 we will test the hypothesis that the ApoE variant that confers the greatest genetic risk to late onset AD in humans, ApoE4, leads to similar alterations in mitochondrial function in brain and skeletal muscle, including promoting a mechanism linked to neurodegeneration in AD: mitochondrial permeability transition (mPT). Furthermore, we also propose that ApoE4 will promote an earlier appearance of neuromuscular impairment and hallmark aging muscle phenotypes that include muscle atrophy, fiber type shift and type-grouping, neuromuscular junction morphological alterations, and accumulation of small angular muscle fibers that are characteristic of persistent denervation in skeletal muscle. These findings would provide important insights to the mechanisms underlying exacerbated skeletal muscle impairment in patients with AD, and identify important features in skeletal muscle that could provide biomarkers for AD risk. In Aim 2 we will test the hypothesis that reducing the Ca2+ threshold for mPT in skeletal muscle will contribute to systemic inflammation that is associated with exacerbated age-related cognitive decline. Conversely, we hypothesize that raising the Ca2+ threshold for mPT in skeletal muscle will attenuate systemic inflammation and cognitive decline compared to normally aging mice. These findings would provide important insights to the potential for mPT occurring in skeletal muscle to contribute to cognitive decline with aging and provide insights to its potential as a therapeutic target for better preserving cognitive function with aging.

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Shinichi Someya

Roles of Sex Chromosomes in Hearing and Balance

 Principal Investigator: Shinichi Someya, PhD

Hearing loss is the third most prevalent chronic health condition in older adults, and age-related hearing loss (ARHL) is associated with increased incidence of dementia, fall-related injury, and mortality. Interestingly, biological sex greatly influences hearing, with women displaying better high-frequency hearing compared to men. A key unmet need in the hearing and aging research fields is to identify the molecular mechanisms underlying these striking differences in auditory function and susceptibility to ARHL. A central biological gender difference is that females have two X chromosomes and males only one. To achieve a balanced X-linked gene expression dosage between females (XX) and males (XY), one of the female X chromosomes is epigenetically inactivated. Despite this X chromosome inactivation (XCI), some X-linked genes consistently escape XCI across tissues and species. These “escapees” have higher expression in XX cells than XY cells, and are important contributors to sex differences in health and diseases. Our overarching hypothesis is that sex chromosome dosage (SCD) effects contribute to the improved auditory function in females. To test this hypothesis and generate key preliminary data for a future R01 application, we propose the following aims using mouse models: Aim 1. Investigate how sex chromosomes and gonads affect hearing function and balance performance. Aim 2. Investigate how sex chromosome and gonads affect mitochondrial function in the inner ear. Outcome/Impact. This study will: 1) allows us to generate key preliminary data for a future R01 application, 2) provide mechanistic insights into why females hear better than males, and 3) may contribute to the development of novel therapeutics that can improve hearing and balance in both males and females.

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Jessica Allen

Neuromuscular Control of Balance During Walking as a Determinant of Community Mobility and Fall Risk in Older Adults

Principal Investigator: Jessica Allen, PhD

Despite conventional diagnostic and rehabilitative efforts, our rapidly aging population remains at a high risk of debilitating falls. We posit that a critical gap limiting the effectiveness of current interventions is a lack of fundamental understanding of how balance is controlled while walking in complex, real-world conditions in which falls occur. Our long-term goal is to advance fundamental knowledge on the neuromuscular control of balance in walking to guide the development and assessment of interventions for improving community mobility and reducing falls in older adults. Our exciting preliminary data identified a novel mechanism of neuromuscular control that, if confirmed in our proposed line of research, could serve as a target to assess and improve the control of balance in walking. Specifically, we found that many of the muscle coordination patterns (i.e., electromyography-derived motor modules) recruited to maintain standing balance in the presence of external disturbances to standing are also recruited in unperturbed walking in young adults – a phenomenon we refer to as neuromuscular balance generalization. Moreover, we found that recruiting fewer balance-related modules during laboratory-based walking was associated with worse balance and walking performance in multiple populations (e.g., young adults, stroke survivors, and individuals with Parkinson’s disease).

Based on these results, our central hypothesis is that recruiting fewer balance-related modules during walking represents a neuromuscular mechanism limiting real-world mobility and underlying increased rate of falls. In this pilot project, we will leverage the expertise and resources of the UF Claude D. Pepper Older Americans Independence Center (OAIC) to expand our prior work into new directions, including monitoring community mobility and prospective tracking falls. The objectives of this pilot project are to (a) confirm this mechanism in older adults spanning a range of balance ability but without overt musculoskeletal or neurological conditions and (b) demonstrate its importance for real-world mobility function. Specifically, we will identify the relationship between neuromuscular balance generalization and (1) walking balance control within laboratory and real world conditions, (2) community mobility as assessed with wearable sensors worn at over a 14-day period, and (3) both retrospective and prospective fall rates ±6 months from study visit. The data generated from this pilot project will provide support for the importance of neuromuscular balance generalization for community mobility in older adults and provide preliminary data to power a follow-up R01 study prospectively linking neuromuscular balance generalization with community mobility and falls. This line of research is significant because we expect to provide evidence of a novel neuromuscular mechanism governing the control of balance in walking that could inform the design, prescription, and evaluation of mobility and fall-prevention interventions in older adults.

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Siobhan Malany

 Principal Investigator: Siobhan Malany, PhD

The goal of our pilot study is to provide feasibility and supporting data for the use of our 3D muscle microphysiological platform to investigate altered myokine signaling and muscle function in aging as supporting data for future NIH grant applications. This pilot proposal will utilize previously collected patient samples (total patients n=21) to form 3D muscle constructs in our 24-well platform. Patient samples were previously collected allowing for cohorts of young (n=9, 5 male and 4 female), aged (n=9, 5 male and 4 female), and clinically diagnosed sarcopenic (n=3, female). The multi-plexed capabilities of our platform allow us to investigate altered myokine secretions, muscle function, metabolism, and contractile signaling in our muscle constructs to understand how these components are altered in aging and may be influenced by sex. Altered levels of circulating factors previously identified as myokines have been associated with increased risks of frailty and sarcopenia in aging. Notably, affected muscle fiber types and myocellular differences in aging have been reported by sex and remain to be investigated.

Additionally, components related to skeletal muscle function, such as, mitochondrial health, elevated oxidative stress, hyper signaling of protein synthesis and altered mitogen-activated protein kinase (MAPK) signaling have been reported in aging muscle and may contribute to the development of sarcopenia. While a large collection supports skeletal muscle-specific changes and muscle crosstalk with other organ systems, the interplay of these mechanisms in aging and their link to sarcopenia have not been fully investigated partly due to lack of tools and methodologies for investigations. The funds requested in our pilot proposal are to demonstrate the usability of this 3D bioengineered system for future aging-muscle research. From the data collected in this pilot study, we aim to pursue a larger NIH grant to identify biomarkers of muscle-aging and sarcopenia to aid in clinical screening, in deciphering molecular cross-talk between the muscle and other organ systems in aging, and to utilize the platform for evaluating aging-muscle performance with drug testing and development.

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Kerry Costello

Community-Based Biomechanics Assessment: Feasibility and Acceptability in Diverse Populations with Knee Osteoarthritis

 Principal Investigator: Kerry Costello, PhD

Knee osteoarthritis (OA) is a painful disease of the joint that affects over 350 million people worldwide, many of whom are older adults. It is a leading cause of disability and amounts to $27 billion per year in healthcare expenditures in the United States alone. While there is no cure for this disease, atypical biomechanical loading on the knee joint during daily activities has been associated with disease progression and thus may be a way to intervene in the disease course. However, interventions to alter joint loading (e.g., retraining the way someone walks or knee braces) have produced inconsistent treatment effects. Knee OA is a heterogenous disease with numerous risk factors and diverse patient experiences of living with the disease. Thus, a one size-fits-all approach to biomechanical interventions is likely not an appropriate strategy. Large samples, however, are needed to account for patient-specific risk factors in analyses of biomechanics and OA outcomes. This necessitates a ‘re-think’ of traditional biomechanical data collection. New ‘markerless’ motion capture, which utilizes video data and deep learning to provide biomechanical data in much less time than traditional methods, and collection of data in community locations, which reduces barriers to study participation and may increase diversity of study samples, may be ideal tools to advance methods to study biomechanics in OA. The goals of this pilot project are to compare feasibility and acceptability of community-based vs. traditional lab-based data collection. This research will provide critical preliminary data; recruitment, retention, and study protocol details; and stakeholder input via the development of a community advisory board, all of which will inform future multi-departmental, multi-site studies with community partners, working towards patient-specific biomechanical interventions for knee OA. Further, development of this new methodological approach will have widespread utility for the descriptive and longitudinal study of numerous factors associated with mobility and aging.

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