Associations between Dietary Quality, Metabolomics, and Age-related Changes in Physical Function and Frailty in Older Adults
Open Access Depositedmicrobial tryptophan metabolism, which plays a role in immune regulation and chronic inflammation, and long-chain sphingolipid metabolism, which is closely related to lipid remodeling of the cell membranes and metabolic fitness. Collectively, this dissertation highlights that different dimensions of dietary quality capture distinct aspects of diet that have meaningful implications on functional aging and frailty development.
While often perceived as a natural part of aging, the gradual decline in physicaland cognitive functions can precipitate functional impairment and disability. A better understanding of the mechanism underlying these functional declines is necessary to develop timely, sustainable, and cost-effective strategies to preserve functions and mitigate the negative impacts of functional declines as individuals age. Diet quality has been suggested to be an important modifiable factor influencingphysical function and frailty status in older adults. Although prior studies have investigated the role of diet in maintaining physical function in older adults, significant knowledge gaps persist. In particular, a comprehensive evaluation of dietary quality that simultaneously considers adherence to dietary guidelines, dietary diversity, and ultra- processed foods (UPF) consumption is lacking. Moreover, the biological mechanisms through which these different aspects of diet influence trajectories of physical function and frailty, especially at the molecular level, are not yet fully understood. The objectives of this dissertation were to evaluate multidimensional dietary quality in older adults, quantify their associations with trajectories of physical function and frailty, and then explore the potential mechanistic pathways linking diet andfunctional aging. These objectives were addressed through three specific aims. In the first aim, we examined cross-sectional and longitudinal associations between the three complementary dietary pattern scores and changes in physical function and frailty status in older adults. In the second aim, we identified plasma metabolites associated with the dietary pattern scores to characterize metabolomic signatures reflective of the overall diet. In the third aim, we tested whether those identified diet-related metabolites were also associated with physical function and frailty outcomes to explore potential biological mechanisms linking diet to functional aging. We further conducted validation analyses using data from another similar cohort with study participants at a comparable age range to assess the robustness and generalizability of our findings. The results of this dissertation demonstrate that different aspects of dietary quality are distinctly and significantly associated with physical function and frailty trajectories in older adults. Higher adherence to the Dietary Guidelines for Americans was consistently associated with better lower-extremity function and lower frailty index over time. Higher consumption of UPF was associated with less optimal functional outcome and an elevated risk of frailty, with stronger associations observed for grip strength among females. Dietary diversity showed more complex and sometimes adverse associations, likely reflecting the heterogeneity in the nutritional quality of the foods consumed by the participants. Metabolomic profiling identified distinct yet partially overlapping signatures across the dietary patterns. Several diet-related metabolites were also associated withfrailty trajectories, revealing two potential mechanistic pathways linking diet to frailty
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Li_gwu_0075A_17910.pdf | 2026-06-24 | Open Access |
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Supplemental_Materials_of_dissertation.pdf | 2026-06-24 | Open Access |
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Supplemental_Table_15-_metabolites_comparison_across_analyses.xlsx | 2026-06-24 | Open Access |
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