Theses and Dissertations

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Development and evaluation of physical and mental readiness training programs for Army Reserve officer training cadets
(Colorado State University. Libraries, 2024) Newman, Alissa A., author; Nelson, Tracy, advisor; Braun, Barry, advisor; Graham, Daniel, committee member; Cooper, K. Bradford, committee member
Military personnel face myriad stressors in both the combat and training environments, including the singular and combined effects of physical exertion, cognitive overload, sleep restriction, energy insufficiency, ambiguous operational environments, as well as emotional and psychological stress. Though the demands of modern military operations continue to shift with technological advances, humans remain the central element and to be successful in the volatile and uncertain modern operating environments, high levels of both physical and psychological readiness and resilience are required. As failure to meet these demands can have catastrophic consequences, the military has placed a high emphasis on the development of physical and mental fitness, with each branch developing their own programs and initiatives. In 2019, the Army introduced its Holistic Health and Fitness (H2F) system, with the aim of improving individual warfighter health and wellbeing as well as overall operational readiness. While H2F is a step in the right direction for the Army as a whole, non-Active-Duty components may have difficulty implementing the system. Reserve Officer Training Corps (ROTC) programs often have limited access to the space, time, equipment, and expertise needed to optimally promote physical and mental readiness. ROTC cadets will commission as officers upon their graduation, will serve in leadership roles, and will be expected to perform at a high level both physically and mentally. Importantly, ROTC programs produce approximately 70% of the officers entering the Army each year and their preparedness, or lack thereof, has substantial impact on those they lead. The feasibility of delivering physical and mental readiness training programs in real-time within the Army ROTC environment and under the time and resource constraints is unclear. One possible mechanism for implementing readiness training in ROTC programs is through collaboration with university partners. By developing cross-campus collaborations, ROTC programs can access necessary resources, especially fitness programing, supervision, and support, to bolster readiness and prepare cadets for success as future Officers. The purpose of this dissertation is to explore the development and implementation of physical and mental readiness training programs in an Army ROTC program, specifically through a collaborative effort between Colorado State University's Health and Exercise Science Department and Army ROTC programs. Study 1 evaluated two training programs designed to improve ACFT performance. The first was an adaptation of programs from Army Training Publication 7-22: Holistic Health and Fitness (ATP 7-22) and the other was designed by HES staff. HES staff, including a Certified Strength and Conditioning Coach and undergraduate practicum students, supervised all physical training sessions alongside Army ROTC cadre. While we saw no significant differences between groups, we found a statistically significant improvement in ACFT scores in our collective study cohort. We faced several challenges over the course of the study period, including a global pandemic and severe weather that impacted and cancelled training sessions. Despite this, we showed that it is feasible to provide effective, multidimensional physical training with limited time and equipment, even in the face of unforeseen challenges. In Study 2, we delivered an 8-week mental skills training (MST) program to first- and second-year Army ROTC cadets. Our qualitative findings suggest that the intervention was impactful and that the participants were able to learn and apply the skills taught during the intervention in physical training and academic settings, as well as during their ROTC training. While we did not find any statistically significant performance outcomes, the results of this study demonstrate a positive impact of MST in this population and provide support for the integration of increased MST into the ROTC curriculum. Collectively, these studies show the impact of both physical and mental readiness training interventions in ROTC cadets. Perhaps more importantly, these studies demonstrate the feasibility of conducting such programs in real time, even with limited time and resources, as well as the capacity for a partnership between ROTC and other university academic departments. We believe that this collaboration is a successful model for the integration of H2F into ROTC programs and could be an effective solution to the challenges faced in delivering comprehensive readiness programming to ROTC cadets.
Open Access
Reasons for joining and adhering to a community-based fitness program among middle-aged and older adults
(Colorado State University. Libraries, 2024) Kirksey, Zoe, author; Leach, Heather, advisor; Burke, Kimberly, committee member; Brothers, Allyson, committee member
Purpose: Community-based fitness (CBF) programs address common barriers to physical activity (PA) participation for middle-aged and older adults and can help to increase regular PA. However, engagement in CBF programs among middle-aged and older adults is suboptimal, and those who do join tend to not adhere long-term. This study examined reasons for joining and adhering to a CBF program and explore common characteristics among long-term members. Methods: Observational, cross-sectional cohort study. Participants were monthly paying members of Adult Fitness, a CBF program at Colorado State University. Participants completed a 24-question quantitative survey, and monthly membership length was determined from participant records. To determine reasons for joining and adhering to Adult Fitness, two 5-point Likert scale questions, on a scale from 1(not motivated at all) to 5 (extremely motivated) were used. The response options were the same and consisted of unique aspects of Adult Fitness and replicated responses from a previous study. Frequency statistics were run on both questions and "motivated a great deal" and "extremely motivated" percentages were summed to determine most prevalent reasons for joining and most prevalent reasons for adhering. Long-term adhering members were defined as having a membership length of ≥5 years, and common characteristics were determined by a response that had more than a 50% response rate. Frequency statistics were run on survey questions to determine common characteristics. Results: The survey was distributed to N=151 members, and N=95 returned, for a response rate of 62%. There were n=8 duplicate and incomplete surveys, leaving a total of N=88 surveys included in analyses. Respondents were 70.5% older adults, 65+, 26.1% middle-aged adults, 35-64, and 3.4% young adults 18-34. Respondents were 50% female, and 50% male and average membership length was 132 months, 11 years (SD=142.8 months; range=563 months). For aim 1, the most frequently reported reasons for joining the Adult Fitness program were facilities available which 79.3% selected "motivated a great deal" or "extremely motivated", followed by self-initiated search for an activity program, 74.7%, and low cost, 60%. Most frequently reported reasons for adhering, were self-initiated desire to promote fitness and/or overall health, 95.4%, facilities available, 80.4%, and low cost, 60%. For aim 2, long-term adhering members (N=58) were motivated to join due to facilities available or self-initiated search for an activity program, motivated to adhere due to self-initiated desire to promote fitness and/or overall health, facilities available, and low cost, reported their current physical as either "good" or "very good", selected either "improvement of health" or "help me stay active" as their most perceived benefit of participating in Adult Fitness, attended the program on average of 3-days a week, and participated in 21-60 min of physical activity (PA) outside of Adult Fitness per day. Conclusion and Clinical Implications: The current study offers valuable insight to CBF program staff and organizational leaders. Understanding motivators of joining and adhering to CBF programs can contribute to tailoring these programs to increase membership and promote long-term participation/membership. These strategies may include offering competitive pricing, adding to existing facilities to cater to interest or needs of members and providing educational resources and progress tracking tools to keep members informed of their health status and/or improvement. Future studies are needed to better understand reasons for discontinuing CBF program.
Open Access
Characterization of the Dunkin Hartley guinea pig as a non-transgenic and multimorbid model of brain aging
(Colorado State University. Libraries, 2024) Glennie, Kristen Skye, author; Hamilton, Karyn L., advisor; Moreno, Julie A., advisor; LaRocca, Thomas J., committee member; Santangelo, Kelly S., committee member
Alzheimer's Disease and Alzheimer's Disease Related Dementia (AD/ADRD) affect an estimated 55 million people worldwide; a staggering figure that is expected to grow in the coming years. With this projection looming, we have yet to identify any effective cures, treatments, or preventative strategies. Historically, AD/ADRD research is conducted using genetically engineered pre-clinical models, that express a specific brain aging pathology. Recent discoveries, however, have identified a dynamic whole-body "inflammaging" phenotype that exists with, and likely contributes to, AD/ADRD onset and progression. Currently, we do not have an accessible and tractable preclinical model that naturally mimics the age-related, systemic and progressive neurodegenerative phenotype present in humans. Recent findings, however, suggest the Dunkin Hartley guinea pig (HGP) may address this need. HGPs are known to develop systemic inflammation and progressive age-related comorbidities characteristic of human aging. The presence of this whole-body aging phenotype prompted investigation into the brain. Genetic and transcriptomic analyses found aged HGPs exhibit strong sequence homology, and similar protein expression patterns to human brain aging and AD. Further, immunohistochemical assessment found aged HGPs express markers of neuroinflammation and misfolded proteins in the hippocampus. To further interrogate these novel findings, we examined the histopathology of 4 brain regions often implicated in neurodegenerative decline for evidence of progressive neuropathology. Our results identify the presence of an age related neuroinflammatory and phosphorylated tau phenotype. Findings from this study contribute to the overarching hypothesis that AD/ADRD is a whole-body disease, and ultimately support the goal of closing the existing translational gap between preclinical and clinical neurodegenerative research.
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Association between youth involvement in home/community gardening and health behaviors
(Colorado State University. Libraries, 2024) Perrault, Ashley, author; Li, Kaigang, advisor; Butki, Brian, committee member; Braungart-Rieker, Julia, committee member
American youth are developing risk factors for historically "adult diseases" at increasingly high rates. These risk factors, such as obesity, elevated blood lipid, blood pressure and insulin resistance, put children at a high risk for developing chronic disease early in life, including before reaching adulthood. School gardening programs are effective at improving dietary intake, physical activity levels and BMI of youth. Despite the success of such programs, there is a need for interventions that effectively target child behaviors while at home. Family-based home and/or community gardens may promote child health behaviors similar to those that occur in school-based gardening programs. A home and/or community garden has the added benefit of parental involvement, which has been shown to be essential for effective child health interventions. The current study examined the relationship between youth involvement in a home and/or community garden and various health behaviors. A convenience sample of 124 adults participated in a cross-sectional survey from June – October 2023. Participants answered questions about family and child involvement in a home/community garden, child health behaviors and parent health behaviors. Health behaviors assessed were physical activity minutes, sedentary behavior, frequency of fruit and vegetable intake and mental health symptoms. Independent sample t-tests indicated that gardening youth had lower sedentary time (t(112) = -1.95, p = 0.03), as well as higher frequency of fruit (t(110) = 2.14, p = 0.02) and vegetable intake (t(109) = 2.67, p = 0.004). Parent fruit intake had a positive linear association with child fruit intake (β = 0.51, p = <0.001), as did parent gardening belief (β = 4.04, p = 0.01). Mediation analysis indicated a positive association between path a (gardening status and parent fruit intake: β=3.06, 95% CI: 0.08, 6.03, p = 0.04) and path b (parent fruit intake and child fruit intake: β = 0.48, 95% CI: 0.30, 0.65, p = <0.001). Gardening status was no longer associated with child fruit intake after the inclusion of parent intake (c': β = 1.64, 95% CI: -1.06, 4.35, p = 0.23), suggesting that parental fruit intake fully mediated the relationship between gardening status and child fruit intake. Gardening status had a positive linear association with child vegetable intake (β = 3.4, p = 0.02), as did parent vegetable intake (β = 0.21, p = 0.004). These findings indicate that youth involvement in a family-based home and/or community garden may be associated with positive health outcomes, especially regarding dietary intake. Parental influence was also associated with positive youth health outcomes. Our findings suggest that home and/or community gardens may provide an effective technique for child health interventions.
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Targeting proteostatic maintenance and mitochondrial function with phytochemical compounds in models of brain and skeletal muscle aging
(Colorado State University. Libraries, 2024) Walsh, Maureen Ann, author; Hamilton, Karyn L., advisor; Fling, Brett W., committee member; Moreno, Julie A., committee member; LaRocca, Thomas J., committee member; Santangelo, Kelly S., committee member
There is a growing population of older adults (>65+ years) worldwide that is projected to increase in coming decades, presenting both a challenge and an opportunity. Specifically, age is the number one risk factor for chronic diseases like sarcopenia, the loss of muscle mass and function, and neurodegenerative diseases such as Alzheimer's Disease. The twelve hallmarks of aging are a collection of cellular changes that drive the aging process. Two highly interconnected hallmarks of aging that drive the development and progression of sarcopenia and neurodegeneration are loss of proteostasis (protein homeostasis) and mitochondrial dysfunction. While progress has been made in understanding the etiology of chronic diseases, treatments for age-related chronic diseases affecting skeletal muscle and the brain are lacking. One reason for the lack of effective treatments in humans is the absence of preclinical animal models that recapitulate human aging. However, our group previously identified the Hartley guinea pig as a novel model of brain and skeletal muscle aging. We then treated these guinea pigs with a phytochemical compound to delay the onset and/or slow the progression of brain and skeletal muscle aging. Through the experiments in this dissertation, I observed that: 1.) phytochemical compounds, branded as Protandim, can improve mechanisms of proteostasis independent of changes in mitochondrial respiration in muscle precursor cells; 2.) the phytochemical compound, branded as PB125, can improve mechanisms of skeletal muscle proteostasis in the Hartley guinea pig; 3.) PB125 can also decrease neuroinflammation in the Hartley guinea pig; and 4.) despite the lack of declines in hippocampal mitochondrial respiration with age, Hartley guinea pigs exhibit decreased mitochondrial efficiency. Collectively, this dissertation builds on prior work suggesting that the Hartley guinea pig is a valuable model to test preclinical interventions.
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Neuromuscular electrical stimulation: getting amped up to prevent exercise resistance
(Colorado State University. Libraries, 2024) Bomar, Matthew Charles, author; Bell, Christopher, advisor; Perry, Richard, committee member; Stephens, Jaclyn, committee member
Purpose: Exercise resistance (ER) is characterized by the absence of exercise induced improvements in fat metabolism following a meal. The prolonged sedentary behavior between successive workouts is what contributes to this lack of health improvements typically associated with exercise. The suggested energy expenditure (EE) threshold for avoiding ER is the equivalent of walking ~8,500 steps/day. Population data indicate that the typical adult walks 5,000 steps/day. Neuromuscular Electrical Stimulation (NMES) evokes skeletal muscle contractions and increases EE. This study aims to determine the feasibility of using NMES to increase total daily EE by the equivalent of 3,500 steps, thereby meeting the theoretical threshold sufficient to prevent ER. Methods: Fourteen recreationally active males and females (7/7) underwent measures of resting EE, with and without NMES, and EE while walking 8,500 steps on a treadmill. The duration of NMES sufficient to increase EE to match 3,500 steps was calculated, and then verified with measures of EE while walking 5,000 steps after a bout of NMES. Results: Bland–Altman statistics of agreement were used to assess concordance between the EE associated with walking 8,500 steps (286 ± 64 kcal; mean ± SD), and the EE associated with walking 5,000 steps after NMES (293 ± 65 kcal). The mean difference between the EE values was 7 kcal, and the 95% limits of agreement were -39 to 53 kcal. Implications: These preliminary data suggest NMES can be used to increase total daily EE by the equivalent of 3,500 steps, thereby meeting the theoretical threshold to prevent ER.
Open Access
Novel transcriptomic mechanisms of brain aging
(Colorado State University. Libraries, 2023) Cavalier, Alyssa Nicole, author; LaRocca, Thomas, advisor; Lark, Daniel, committee member; Hamilton, Karyn, committee member; Weir, Tiffany, committee member
As the world ages, the incidence of age-related diseases like dementia is expected to increase. Brain aging is characterized by declines in cognitive function that may develop into mild cognitive impairment, which increases the risk for dementia. In fact, age is the primary risk factor for late-onset Alzheimer's disease, which is the most common age-related dementia. The adverse cellular and molecular processes that underlie cognitive decline with aging in the brain are known collectively as the "hallmarks of brain aging." Advances in next-generation sequencing (e.g., transcriptomics/RNA-seq) have made it possible to investigate age- and disease-related changes in the brain at the broad gene expression level, and to identify potential therapeutic targets. With the support of my committee and mentoring team, I completed three studies using transcriptomics that characterize novel mechanisms that underlie brain aging. My findings include: (1) doxorubicin chemotherapy accelerates brain aging at the gene expression level, (2) apigenin nutraceutical supplementation targets age-related inflammation in the brain and rescues cognitive impairment in old mice, and (3) epigenetic dysregulation of transposable elements (remnants of viral infection in the genome) with aging contributes to age-related inflammation in Alzheimer's disease. Together, my work provides insight into transcripts and cellular/molecular pathways that are modifiable and may be therapeutic targets to delay or prevent consequences of brain aging.
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Effect of a videoconference-delivered physical activity intervention on quality of life in colorectal cancer survivors
(Colorado State University. Libraries, 2023) Prien, Lydia, author; Leach, Heather, advisor; Schmid, Arlene A., committee member; Zimmaro, Lauren A., committee member
INTRODUCTION: Colorectal cancer is the fourth most common cancer diagnosed in both men and women in the United States. For every 100 people diagnosed with colon cancer, 64 are expected to live five or more years after diagnosis. With this growing number of colorectal cancer survivors, quality of life (QOL) becomes an important patient reported outcome within this population. QOL is multidimensional and includes various dimensions of wellbeing (e.g., physical, emotional, social) that can be improved with physical activity. Previous research has established that face-to-face supervised physical activity (PA) interventions can improve QOL among colorectal cancer survivors (CRC) (Mishra et al., 2012). However, these interventions require a lot of resources, and may be difficult to access. Thus, researchers have turned to distance-based physical activity (PA) interventions (digital health tools, text messaging, prerecorded home-based workouts etc.) to increase access and scalability of PA interventions for CRC survivors. Previous studies that have examined the effect of distance-based PA interventions for improving QOL in CRC survivors did not find improvements in QOL. For example, Kim et al. (2019) found no significant improvements in QOL following an unsupervised, homebased, DVD exercise program, and Chan et al. (2022) found no significant changes in QOL, following a text messaging intervention. These finding suggest that distance-based PA interventions may not be as effective as face-to-face for improving QOL in CRC survivors and may be due to a lack of contact with other survivors and/or diminished PA adherence/compliance due to lack of supervision and instruction from an exercise professional. Since the COVID-19 pandemic, videoconference PA interventions have grown in popularity, and may be able to overcome some of the limitations of both face-to-face and distance-based PA interventions for improving QOL in CRC survivors. However, to date there are no previous studies that have examined the effect of a videoconference intervention on QOL in CRC survivors. This study will examine changes in QOL in colorectal cancer survivors following a 12-week, videoconference, PA intervention. This study will be a secondary data analysis of participants enrolled in Testing Group Activity CorrelaTes In Colorectal Cancer Survivors (TACTICS), a pilot randomized controlled trial with the primary aims of determining feasibility, and preliminary effects on physical activity. METHODS: TACTICS is a 12-week pilot randomized controlled trial where the intervention group received group-based exercise sessions 2x/week, and five behavior change discussion sessions delivered via Zoom. The control group received standard physical activity recommendations. QOL was measured at baseline and 12-weeks using the Functional Assessment of Cancer Therapy–Colorectal (FACT-C). Mean change, standard deviation, and effect size were reported to measure improvements in QOL. Established minimal clinically important differences (MCID) are a Δ5 points for total and a Δ2 points for QOL subscales. The proportion achieving MCID's in intervention vs. control were compared using Fisher's Exact tests, and independent t-tests or chi square tests explored differences in participant characteristics between those did vs. did not achieve MCID. RESULTS: Participants (n= 13 intervention, n=12 control) were mostly 56% female and M=61.2±11.7 years old. Among intervention participants, proportion who achieved MCID was 23.1% total, 15.4% physical, 38.5% functional, 23.1% social, and 15.4 % emotional, compared to 41.7% total, 33.3% physical, 25.0% functional, 41.7% social wellbeing, and 16.7% emotional among control. None of these proportions differed between groups (p>.05). For the physical QOL subscale, BMI was higher [t(11)=2.92, p=.014] and baseline scores were lower [t(7)=-2.34, p=.052] among those who achieved MCID. CONCLUSION: We observed small improvements in QOL within CRC survivors. There were no statistically significant differences in achieving clinically relevant improvements in QOL between intervention and control group participants. Larger randomized studies are needed to definitively determine if a videoconference exercise intervention can elicit clinically relevant improvements in QOL compared to a control group.
Open Access
Exploring cancer survivors' preferences for a physical activity maintenance program
(Colorado State University. Libraries, 2023) Anderson, Hadalyn, author; Leach, Heather, advisor; Fruhauf, Christine, committee member; Faro, Jamie, committee member
Purpose: Physical activity (PA) offers long-term health benefits for cancer survivors (CS), if sustained. Community-based exercise programs have shown short-term effectiveness in increasing PA among cancer survivors, but evidence of their effect on long-term PA engagement (i.e., PA maintenance) is lacking. This study (1) quantitatively explored cancer survivors' preferences for a PA maintenance program and whether preferences were impacted by PA levels, and (2) qualitatively explored participants' preferences of a PA maintenance program and PA-related barriers. Methods: CS who completed one of three original cancer-specific community-based exercise programs participated in a pilot PA maintenance program (i.e., two exercise and discussion sessions). (1) Participants completed questionnaires via REDCap database to assess interest in a PA maintenance program (i.e., likelihood of attending, perceived helpfulness and enjoyment, and preferences of frequency, duration, and time until maintenance program commencement) and PA levels. Participants reported current PA levels compared to when they finished the original program (greater or same vs. lower PA levels) and completed the Godin Leisure-Time Exercise Questionnaire to determine whether they were currently meeting PA guidelines (≥150 mins/week of moderate aerobic PA + 2 days of strength training). (2) Participants also completed semi-structured focus groups via Zoom that aimed to answer the following questions regarding participants': (i) maintenance program experience, (ii) suggestions for future maintenance program implementation, (iii) perceived elements of the original program that were helpful in maintaining PA, and (iv) barriers experienced following the original program. Frequencies from (1) were calculated, and Fisher's exact tests were used to compare proportions between maintenance program preferences and participants' PA levels. Qualitative data from (2) were transcribed verbatim, coded inductively, and analyzed using thematic analysis. Themes and frequencies of references (%) were calculated. Results: (1) Participants (N=20) were M=60±13 years old, non-Hispanic White (95%), female (95%), and diagnosed with breast (50%), ovarian (20%), or other (30%) cancer. Average time since program completion was M=26.2 ± 35.7 (1-110) months. Most participants (65%) reported exercising more or the same amount since original program completion, and 35% met PA guidelines. The majority were likely to attend maintenance exercise (90%) and discussion (80%) sessions. All (100%) participants thought maintenance exercise sessions would be helpful and most (85%) for discussion sessions. There were no differences in responses based on PA levels (all p>.05). (2) Themes identified for (i) were Accountability (36%), Shared Cancer Survivor Experience (26%), Individualized Exercise Prescription (30%), and Discussion Session Content (8%); (ii) were Accountability (8.929%), Discussion Session Content (26.79%), and Discussion (19.64%) and Exercise (44.64%) Session Delivery; (iii) were Accountability (39.39%), Individualized Exercise Prescription (30.3%), and Discussion Session Content (30.3%); and (iv) were Psychological (41.38%), Physical (27.59%), and Environmental (31.03%). Conclusion: Participants had positive perceptions of the maintenance program. Future studies should measure effectiveness of a maintenance program to support PA maintenance and encompass program leader perspectives to work towards achieving pragmatic solutions to maintain PA maintenance programs within community-based settings.
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How are driving licensure status, delay in driving licensure, and driving exposure associated with alcohol and drug use, parental monitoring knowledge, peer alcohol and drug use, and health, education, and employment of emerging adults?
(Colorado State University. Libraries, 2023) Gao, Xiang, author; Li, Kaigang, advisor; Vaca, Federico E., committee member; Sharp, Julia, committee member; DeYoung, Wendy, committee member
Independence and mobility facilitated by driving privileges could have a major impact on alcohol and drug use, parental monitoring knowledge, peer alcohol and drug use, and health, education, and employment of emerging adults. Driving privileges may provide emerging adults with the ability to move more freely, and that mobility may affect their access to drugs and alcohol. It may also mean that emerging adults with driving privileges were more likely to be in environments where alcohol and drugs were available. Parents of emerging adults with driving privileges may be more involved in monitoring their child's driving activities, resulting in higher levels of parental monitoring knowledge. Emerging adults with driving privileges were more likely to report a higher level of peer alcohol and drug use because having access to a car allowed them to spend more time with their peers and engage in alcohol and drug use. On the other hand, driving privileges may have positive impacts on the health, education, and employment of emerging adults. Having the ability to travel to places of employment and educational institutions may open more opportunities and allow for greater access to resources. This could lead to improved academic and professional outcomes. Overall, driving privileges may have both positive and negative impacts on alcohol and drug use, parental monitoring knowledge, peer alcohol and drug use, and health, education, and employment of emerging adults. It was important to consider these trade-off impacts when considering how to best support emerging adults in their development. My dissertation explored how were driving licensure status, delay in driving licensure, and driving exposure associated with alcohol and drug use, parental monitoring knowledge, peer alcohol and drug use, and health, education, and employment of emerging adults. Data was collected from a nationally representative sample of U.S. emerging adults starting at grade 10th for a seven-year longitudinal assessment. Having driving licensure in high school, no delay in driving licensure, and higher driving exposure were associated with higher levels of alcohol and drug use, higher levels of parental monitoring knowledge, higher levels of peer alcohol and drug use, better health, higher levels of education attainment, and more working hours in emerging adulthood. My dissertation could inform policymakers and practitioners on the importance of driving privileges in promoting the well-being of emerging adults.
Open Access
Identifying novel molecular mechanisms of healthspan using multi-omics
(Colorado State University. Libraries, 2023) Smith, Meghan Elizabeth, author; LaRocca, Tom, advisor; Hamilton, Karyn, committee member; Broussard, Josiane, committee member; Ehrhart, Nicole, committee member
An important goal in research on aging is to extend healthspan, the period of life spent healthy and disease-free. Next-generation sequencing and other emerging bioinformatics technologies (e.g., RNA-seq/transcriptomics, epigenetic profiling, and proteomics) have made it possible to broadly profile potential molecular mediators of aging, and perhaps identify therapeutic targets. The studies in this dissertation focus on using transcriptomics and complementary "multi-omics" strategies to characterize novel cellular mechanisms of aging, and to determine their relevance to systemic/functional health in humans. With the guidance of my mentoring team, I completed three studies in which I identified novel mediators of healthspan-related exercise training responsiveness, age-related inflammation, and cognitive/motor function decline in middle-aged and older adults. One particularly novel focus among these studies was the role of non-coding repetitive RNAs (derived from transposable elements) in healthspan. Transposable elements have been linked to known mechanisms of aging, and this topic is reviewed at the start of this dissertation to provide perspective on their role in the context of research on aging biology. Collectively, my findings represent new ideas for targetable genes and proteins that may influence human healthspan.
Open Access
The transcallosal highway: the ipsilateral silent period as a neural biomarker for impaired corpus callosum communication and gait asymmetry in people with multiple sclerosis
(Colorado State University. Libraries, 2023) Acosta, Jordan, author; Fling, Brett, advisor; Rudolph, Alan, committee member; Miravalle, Augusto, committee member; Schmid, Arlene, committee member
Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in transcallosal communication impairs the coordination of gait which requires constant communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of transcallosal communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of transcallosal inhibition in PwMS. This study utilizes transcranial magnetic stimulation (TMS) to assess the inhibitory capacity between the brain's hemispheres. There is a lack of research analyzing directionality data between the more and less affected hemisphere in PwMS. Therefore, we evaluated outcome metrics dependent upon the individual's more affected hemisphere calculated from the subject's more affected limb observed during walking assessments and self-report. We hypothesize that the iSP may serve as a neural biomarker for transcallosal impairments evaluated by directionality differences between the hemispheres and highlight transcallosal inhibition as an underlying neural mechanism for gait asymmetries in PwMS. From twenty-nine PwMS, metrics such as depth iSP% average, duration, depth iSP% max, and onset latency were collected. No statistically significant differences were found between the two hemispheres. This suggests that PwMS may be able to preserve their interhemispheric inhibitory capacity irrespective of their more affected hemisphere. Additionally, another component of the study investigated gait coordination utilizing a split-belt treadmill training paradigm. Limb excursion asymmetry (LEA) measures, pre and post-training, were analyzed for spatial coordination and as a measurement of locomotor adaptability in PwMS. The relationship between LEA change and dSP% average highlighted a significant correlation (r=0.46, p= 0.02). Thus, showing that less interhemispheric inhibition corresponds with more spatial adaptability leading to a more symmetric gait. These findings may help determine the potential of iSPs as a neural biomarker to address gait asymmetries and stratify participants into mobility rehabilitation protocols.
Open Access
The effects of sleep extension on physical and cognitive performance in AROTC cadets
(Colorado State University. Libraries, 2023) Wedderburn, J'Michael, author; Broussard, Josiane, advisor; Lipsey, Tiffany, committee member; Eakman, Aaron, committee member; Brager, Allison, committee member
College students and military personnel have limited sleep opportunities; Reserve Officer Training Corps (ROTC) cadets belong to both groups. Thus, cadets are at a heightened risk of insufficient sleep. Sleep loss can have deleterious effects on physical and cognitive health (Halson et al., 2014). In military professions, these impairments have potentially fatal consequences, as decreased performance will result in diminished operational readiness. Recent evidence suggests that sleep extension is a valid intervention to increase sleep duration (Bonnar et al., 2018). Thus, we aim to identify if sleep extension improves performance in chronically sleep-deprived ROTC cadets. This study examines the impact of 1-week of sleep extension on physical and cognitive performance in Army ROTC cadets. We recruited 16 healthy, active male and female participants aged 18-35 from Colorado State University's ROTC program. Participants were equipped with Actiwatches and completed daily sleep questionnaires and diaries during the habitual and sleep extension periods. Sleep extension was achieved by asking participants to spend 10 hours in bed to increase sleep by at least 1 hour per night. Cadets then completed a series of physical and cognitive tests to measure performance on tactically relevant tasks. The physical testing consisted of a vertical jump, 3-repetition maximal hexagon deadlift, 300-meter shuttle, and a 1-mile run; and cognitive test consisted of a psychomotor vigilance test, the Purdue pegboard test Tiffin (1948), the STROOP color-word test Jensen (1965), and a simulated shooting exercise. Wilcoxon Signed rank-test and two samples paired t-test statistical analysis compared baseline, physical, and cognitive testing data to post-intervention testing data. Cognitive and physical testing occurred after 1-week of habitual sleep and 1-week of sleep extension. The mean objective Total Sleep Time (TST) was 6.07 ± 0.15 hours during the baseline period and 7.03 ± 0.17 hours during the sleep extension period (P=<0.0001). The mean Epworth Sleepiness Scale (ESS) rating was outside of normal limits at 10.47 ± 1.16 during the habitual sleep period; it decreased to fall within the normal limits during the sleep extension period at 7.10 ± 0.79 (P <0.005) (Shattuck & Matsangas. 2014). There were statistically significant differences found on 2 of the 4 Purdue pegboard tests and deadlift performance from habitual sleep to the sleep extension period. The mean hands and assembly scores significantly improved (P = 0.038 and P=0.003, respectively). Performance on the 3-repetition maximal hexagon deadlift increased significantly during the habitual sleep period and sleep extension period (p = .007). The limited sleep opportunities ROTC cadets encounter have negative implications on physical and cognitive performance; based on our findings in the current study, it is plausible that sleep was not extended to an adequate duration to elicit cognitive and physical performance improvements in all of the tested cognitive and physical measure. Thus, more research is needed to investigate the relationship between sleep duration and sleep quality and their effect on cognitive and physical performance in tactical population.
Open Access
The effect of circadian regulation and sleep disruption on metabolic homeostasis
(Colorado State University. Libraries, 2022) Morton, Sarah J., author; Broussard, Josiane L., advisor; Hickey, Matthew S., committee member; Dinenno, Frank A., committee member; Bergman, Bryan C., committee member; Prenni, Jessica E., committee member
Sleep and circadian disruption are ubiquitous in modern society. While the National Sleep Foundation recommends adults sleep 7-9 hours per night, the average sleep duration of American adults has decreased from ~8.8 hours to ~6.8 hours over the last century, with 1 in 3 people report sleeping fewer than 6.5 hours per night during the work week. People who sleep fewer than 6 hours per night have a three-fold risk of impaired fasting glucose than those sleeping at least 8 hours per night. Laboratory studies report that as little as one night of insufficient sleep impairs insulin sensitivity, which is a common risk factor for obesity and diabetes. Circadian misalignment is common in people who work non-standard hours, including evening, night, or rotating shifts, and is associated with increased fasting glucose and insulin concentrations, as well as impaired insulin sensitivity. Moreover, circadian misalignment can also occur as a consequence of insufficient sleep. With more than 35% of adults reporting insufficient amounts of sleep, chronic and acute circadian misalignment are likely even more prevalent than commonly recognized. Sleep and circadian disruption are associated with increased mortality rates and health problems, including obesity and diabetes. However, the molecular mechanisms by which these impairments occur are not known. Thus, the overall goal of this dissertation was to determine the circadian rhythms of substrate oxidation and hormonal regulators of energy balance as well as to identify molecular alterations associated with insufficient sleep, including skeletal muscle lipid accumulation and altered gene expression, and their relation with insulin sensitivity. The primary findings are that in healthy, young, lean participants 1) carbohydrate and lipid oxidation as well as ghrelin and peptide YY have circadian rhythms as identified by a constant routine protocol and 2) insufficient sleep induces skeletal muscle lipid accumulation and altered gene expression as well as impaired insulin sensitivity. Together, these studies indicate that sleep and circadian disruption may impair insulin sensitivity via dysregulated lipid metabolism.
Open Access
Short-term metabolic effects of breaking up sedentary behaviors
(Colorado State University. Libraries, 2022) De Jong, Nathan Paul, author; Hickey, Matthew S., advisor; Bergouignan, Audrey, committee member; Braun, Barry, committee member; Melby, Christopher L., committee member
"Sit Less, Move More" has become a widespread public health message due in part to the recognition that sedentary behaviors (i.e., sitting) are associated with all-cause mortality and increased risk for obesity, diabetes, cardiovascular diseases and some cancers, even when accounting for time spent in moderate-to-vigorous physical activity. Recent epidemiological and experimental evidence from acute and short-term studies indicate that reducing and breaking up sedentary behaviors (i.e., sitting) may be a useful strategy for glucose control. Acute experimental trials (5-12 hr exposure) demonstrate that breaking up sedentary time with short-frequent bouts of physical activity is associated with lower postprandial glucose and insulin concentrations while a time-matched single-continuous bout is associated with lower postprandial triglyceride concentrations in response to standardized meals. This suggests differential substrate oxidation may be responsible for the changes in postprandial metabolites. However, what is unknown is (1) whether breaking up sedentary behaviors with short-frequent bouts of physical activity is a strategy that can be implemented in the daily life of sedentary, physically inactive adults; (2) whether the acute metabolic benefits previously observed are sustained or diluted beyond the acute exposure period (> 5-12 hr); (3) whether the effects are due to the active breaks per se or to increases in total energy expenditure and/or total active time and (2) the characterization of potential underlying physiological, cellular, and molecular mechanisms. The primary objective of this dissertation is to investigate the feasibility of implementing short-frequent bouts of physical activity to break up sedentary behaviors into daily life over the short-term (4-day) in those who are habitually inactive and the effect on nutrient metabolism when energy expenditure and balance are matched. We hypothesized that breaking up sedentary behaviors with short-frequent bouts of physical activity is a feasible lifestyle intervention to increase physical activity which will be associated with attenuated glycemia by an increase in postprandial carbohydrate oxidation. In a randomized cross-over study, we compared the short-term effects (4-day) of breaking up sedentary behaviors with short-frequent bouts of moderate intensity physical activity (MICRO: 5-min walk bout every hour for 9 consecutive hours per day) to a time-matched single-continuous bout of moderate intensity physical activity (ONE: 45-min continuous walking bout per day), and a sedentary control (SED: habitual sedentary behaviors and physical inactivity each day) in inactive male and female adults with overweight or obesity. To reach our overall objective, three independent specific aims were pursued: 1) to determine the feasibility of implementing MICRO compared to ONE on daily time spent sitting and physically active over the short-term; 2) to determine the effect of MICRO compared to ONE on nutrient metabolism and insulin sensitivity; 3) to characterize the short-term effect of MICRO compared to ONE on permeabilized skeletal muscle fiber respiration and gene expression of proteins involved in the regulation of metabolic pathways. Results from this dissertation demonstrate that 1) MICRO is a feasible intervention to promote physical activity both on workdays and non-working days in those who are at high risk for metabolic disease; (2) At the same energy expenditure and balance, MICRO resulted in a greater reliance on carbohydrate as fuel during the waking period when the bouts were performed and over 24 hr. In contrast, a single isoenergetic continuous bout of moderate intensity walking increased 24 hr total and dietary fat oxidation. Both physical activity interventions lowered postprandial insulin and improved fasting indexes of insulin sensitivity compared to SED; 3) While no changes were observed after MICRO in mitochondrial oxidative capacity, MICRO is a sufficient stimulus to promote adaptations in skeletal muscle augmenting pathways associated with substrate oxidation. Independent of detectable differences in insulin sensitivity, total active time, and energy expenditure, breaking up sedentary behaviors with short-frequent bouts of physical activity spread throughout the day is a viable lifestyle intervention for glucose control compared to the same amount of physical performed as a single continuous bout with the rest of the day spent sedentary. This evidence can be used to refine future physical activity guidelines to prevent and treat metabolic diseases, not in terms of intensity of exercise per day per week but in terms of avoidance of sedentary activities through short bouts of physical activity.
Open Access
Determinants of driving performance following stroke
(Colorado State University. Libraries, 2022) Pollet, Aviva Katherine, author; Lodha, Neha, advisor; Li, Kaigang, committee member; Schmid, Arlene A., committee member
Overall introduction: Individuals with stroke experience motor and cognitive deficits both of which can impact driving performance. Using two separate studies, we evaluated the influence of motor and cognitive factors on driving performance in stroke survivors. In the first study, we evaluated how driving impairments in stroke survivors is influenced by the use of either the paretic or non-paretic leg for pedal control. Methods 1: Twenty-two individuals with chronic stroke were recruited in two groups depending on their lower-limb choice for pedal control 1) paretic leg drivers, individuals using their paretic leg to control the car pedals (N = 11, 68.4 ± 7.8 years) and 2) non-paretic leg drivers, individuals using their non-paretic leg to control the car pedals (N = 11, 61.1 ± 13.7 years). Both groups performed a car following task in a driving simulator. The task required participants to follow a lead car by controlling the gas pedal accurately and respond to brake lights by pressing the brake pedal as fast as possible. We quantified gas pedal error using root mean square error (RMSE). We measured brake response time as the time from the onset of the brake lights of the lead car to the application of the brake pedal. We also dissociated the brake response time into pre-motor and motor response times. We used the Driving Habits Questionnaire (DHQ) to measure self-reported on-road driving behavior. Additionally, using surface electromyography (EMG), we analyzed neuromuscular activation using burst duration and amplitude, and coordination using overlap and coactivation of the tibialis anterior (TA) and medial gastrocnemius (MG) during the braking portion of the car following task. Results 1: The paretic leg drivers showed greater gas pedal RMSE than the non-paretic leg drivers (p ≤ 0.01). The paretic leg drivers had a slower brake response time than the non-paretic leg drivers (p < 0.05). Premotor response time was not different between the two groups (p = 0.71), however, the paretic leg drivers had a significantly slower motor response time relative to the non-paretic leg drivers (p < 0.05). The paretic leg drivers had lower DHQ scores than the non-paretic leg drivers (p ≤ 0.01). DHQ and brake response time were negatively correlated (r = - 0.42, p ≤ 0.05). Additionally, paretic leg drivers showed longer TA EMG burst duration (p <0.05) and more TA-MG overlap (p <0.05). TA EMG burst duration was positively correlated to brake response time (r = 0.51, p < 0.05) and motor response time (r = 0.61, p < 0.05). TA-MG overlap was positively correlated to brake response time (r = 0.76, p = 0.001). In the second study, we evaluated how cognitive load influenced driving impairments in stroke survivors. Methods 2: Ten individuals with chronic stroke participated in the current study (N = 10, 65.6 ± 14.9 years). The participants performed simulated driving without (single-task) and with (dual-task) a cognitive load. The single-task driving required participants to drive along a rural road and brake as quickly as possible when an unexpected hazard, such as wildlife crossing into the driving lane, was encountered. The dual-task driving required participants to drive in the same driving scenario while performing a secondary cognitive task. The cognitive task involved mental arithmetic to induce higher cognitive load while driving. Specifically, participants were asked to subtract 4 and add 3 to a random number and do so repeatedly until the end of the driving task. We measured lane departures as the number of times the edge of the participant's vehicle left the designated driving lane. We measured speed compliance as the percent of total time the individual was within +/- 5 MPH of the speed limit between events. Additionally, we measured brake response time as the time from the appearance of the hazard stimulus to the application of the brake pedal. Results 2: Individuals with stroke show more lane departures throughout the entire drive during dual-task driving than single-task driving (p < 0.05). Additionally, individuals with stroke show worse speed compliance during dual-task driving than single-task driving (p < 0.05). There was no difference in brake response time between the single-task and dual-task driving (p = 0.18). Overall conclusion: Driving performance in stroke survivors is influenced by limb selection for pedal control and cognitive load. The current studies demonstrate the need to assess and train motor and cognitive deficits that contribute to driving performance in individuals with stroke. Motor deficits in pedal control and brake response time contribute to unsafe driving in individuals with stroke. Cognitive deficits in lane departures and speed compliance in driving with cognitive load also contribute to unsafe driving in individuals with stroke. To address these deficits, stroke driving rehabilitation programs should focus on driving leg and cognitive environment of driving.
Open Access
Brain protein synthesis rates and energy sensing in sulfur-amino acid restricted mice
(Colorado State University. Libraries, 2022) Martinez, Wenceslao, author; Hamilton, Karyn, advisor; LaRocca, Thomas, committee member; Moreno, Julie, committee member
Protein homeostasis (proteostasis) is the maintenance of the cellular proteome through protein synthesis, folding, trafficking, and degradation. Loss of proteostasis is considered one of the hallmarks of aging and is a driver for age-related neurodegenerative diseases. Dietary sulfur amino acid restriction (SAAR), a life-/healthspan extending treatment, activates mechanisms that maintain proteostasis in the liver. However, it is unknown if dietary SAAR activates mechanisms promoting proteostatic maintenance in the brain. To address this knowledge gap, wild-type male C57Bl/B6 mice were fed one of two levels of SAAR (expressed as % kcal); 0.18% methionine and 0% cysteine (Low SAAR) or 0.12% methionine and 0% cysteine (High SAAR), or a matched control diet sufficient (0.85-0.88%) in methionine. Deuterium enriched water was used to measure rates of newly synthesized proteins and DNA (as a marker of cellular proliferation). Brains were collected at days 1, 3, 7, 14, 21, and 35 of treatment. Mitochondrial, cytosolic, and mixed fractions of frontal cortex were analyzed for rates of protein synthesis and cell proliferation using GC/MS. A one phase association was used to determine the rate of the rise of newly synthesized protein and DNA to capture the kinetic parameter k (1/d). Phosphorylated and total protein content for AMP-protein kinase (AMPK), ribosomal Protein S6 (RPS6) and eukaryotic Initiation Factor 2 (eIF2) were measured at day 1 (acute) and day 35 (long-term) via western blot. Mitochondrial protein synthesis rates were significantly greater in the Low SAAR diet compared to the matched control diet, but did not differ in the cytosolic and mixed fractions. Protein synthesis rates in all fractions of the High SAAR diet were not different from control. There was no significant difference in cell proliferation rates between the SAAR diets and their control matched diets. However, in the High SAAR diet, as reflected by greater protein synthesis to DNA synthesis ratios, more newly synthesized proteins were allocated toward mitochondrial proteome maintenance rather than cell proliferation compared to control. At day 1, eIF2 activation tended to greater (p=0.0922) in the Low SAAR diet compared to control, but was not different at day 35 in the Low SAAR or High SAAR diets. AMPK activation did not differ in the Low SAAR or High SAAR diet compared to their controls at day 1 and day 35. RPS6 activation was not significantly different at day 1 or day 35 in either SAAR diet compared to their controls. This is the first study to simultaneously assess rates of protein synthesis and cell proliferation in the frontal cortex during dietary SAAR, as well as assess activation of key energy sensing proteins. The results from this study show that despite restriction of the sulfur amino acids, rates of protein synthesis were maintained in the cytosolic and mixed fractions with Low SAAR, while the rate of mitochondrial protein synthesis was greater than the control group with Low SAAR but not High SAAR. Dietary SAAR also promoted allocation of more newly synthesized proteins towards maintenance of the existing proteome, with less for new cell proliferation.
Open Access
Caffeine augments the lactate and interleukin-6 response to moderate-intensity exercise in males but not females
(Colorado State University. Libraries, 2022) Abbotts, Kieran Shay Struebin, author; Bell, Christopher, advisor; Hamilton, Karyn, committee member; Melby, Christopher, committee member
The release of interleukin (IL)-6 from contracting skeletal muscle is thought to contribute to some of the health benefits bestowed by exercise. This IL-6 response appears proportional to exercise volume. Unfortunately, high volumes of exercise are not feasible for all people. Caffeine augments the magnitude of increase in circulating concentration of IL-6 in response to high-intensity and long-duration exercise, in males. Caffeine is also known to increase circulating concentrations of lactate during exercise. One of the mechanisms thought to contribute to IL-6 release from exercising skeletal muscle is lactate production. We hypothesized that caffeine, ingested prior to moderate-intensity exercise, would lead to greater circulating concentrations of lactate and IL-6 in a study population comprising both males and females. 15 healthy adults (9 males and 6 females, aged 26±7 years, (mean ± SD)) completed 30-minutes of moderate-intensity cycle ergometer exercise, equivalent to the ventilatory threshold, after ingesting either caffeine (6 mg/kg) or placebo. Arterialized-venous blood was collected throughout each of the exercise sessions. Compared with placebo, caffeine increased end-exercise circulating concentrations of lactate (5.72±3.95 vs. 7.14±4.66 mmol/L, P<0.001) but not end-exercise IL-6 (1.84±0.97 vs. 2.37±1.04 pg/mL, P=0.139). However, when females were excluded from the analysis, caffeine augmented (P=0.04) the magnitude of increase of end-exercise IL-6 concentration (1.80±0.86 vs. 2.57±1.21 pg/mL); this effect was further exaggerated after 30-minutes of inactive recovery (3.81±2.32 vs. 5.06±3.22 pg/mL). Noteworthy, caffeine evoked greater end-exercise lactate concentrations in data sets containing only males (P=0.02) and only females (P=0.002) but did not influence the IL-6 response in females (P=0.94). Our preliminary data imply that in males unable/unwilling to perform high-intensity and/or long-duration exercise, caffeine may potentially enhance the IL-6 mediated health benefits of relatively short, moderate-intensity exercise.
Open Access
Bayes'd and confused: novel applications of Bayesian inference to better understand sensorimotor uncertainty
(Colorado State University. Libraries, 2021) Whittier, Tyler Thorley, author; Fling, Brett W., advisor; Rhea, Christopher K., committee member; Seidler, Rachael D., committee member; Weller, Zachary D., committee member
Effective motor control relies on accurate sensory information. However, sensory information is inherently variable and clouded with uncertainty. Yet, humans perform motor skills with a high degree of proficiency and reliability. How the central nervous system (CNS) controls motor function amid the uncertainty of sensory signals is not known. Researchers in recent years have suggested that the brain may control movement in a way that can be explained by Bayesian inference. Bayesian inference posits that the most probable outcome is the product of both the currently available data (sensory information) as well as previously collected data (learned expectations). Applying Bayesian inference to a motor control context, we suggest that the CNS accounts for the uncertainty in sensory information by filling in the gaps of uncertainty with learned expectations when forming beliefs on where our body parts are in space. While initial findings on this topic are promising, they predominantly involve one-dimensional upper-body tasks. The purpose of this dissertation was to determine if Bayesian model of sensorimotor control is consistent in a full body stepping movement and if it can be further utilized to understand sensory function in various contexts. The first study in this dissertation was done to discover if the center of mass (CoM) position is estimated in a Bayesian way during stepping, like what has been shown in upper body movements. The second study sought to identify if Bayesian position estimations are beneficial to overall motor performance. In the third study, we applied what we have discovered about Bayesian inference in full body movements to understand the effects of transcutaneous electric nerve stimulation (TENS) on positional awareness during motor control. We hope to build on these findings to better understand how sensory information is utilized by the CNS to control movement.
Open Access
Novel modulators of blood pressure with age: a physiological and bioinformatics-based approach
(Colorado State University. Libraries, 2021) Bachman, Nate P., author; Braun, Barry, advisor; LaRocca, Thomas J., advisor; Chicco, Adam J., committee member; Gentile, Christopher L., committee member
Systolic blood pressure (SBP) increases with age and is a significant risk factor cardio- and cerebrovascular diseases. While the causes of high blood pressure (hypertension) have been extensively studied, the causes of the age-related rise in blood pressure independent of chronic disease remain unclear. Thus, the identification of novel mechanisms underlying age-related high blood pressure may lead to new strategies to reduce chronic disease risk in older adults. Therefore, the goal of this dissertation was to use both physiological and bioinformatics-based approaches to better elucidate contributors to elevated blood pressure in healthy older adults. The main findings are that 1) inhibition of Rho-kinase (an enzyme that participates in numerous cellular/regulatory pathways) lowers systemic blood pressure in healthy older adults concomitant with reduced vascular resistance but not improved endothelial function, 2) genes expression patterns in peripheral white blood cells differ in healthy older adults with elevated SBP compared to those with normal SBP and transcriptomic (RNA) changes relate to vascular and immune function, and 3) circulating chemokines and whole blood immune-related transcripts track with elevated SBP in healthy older adults. Taken together, this work shows that Rho-kinase, circulating RNA transcripts, and circulating chemokines may be novel therapeutic targets and/or biomarkers of elevated blood pressure in healthy older adults with untreated hypertension.