Sleep and Rest-Activity Rhythms and Cardiovascular Health in the Elderly: the Role of Metabolomics and Inflammatory Pathways

2020 Strategic Research Grant

Qian Xiao, PhD
The University of Texas Health Science Center at Houston School of Public Health

Key Project Outcome

Our AASM Foundation Strategic Research Grant has led to improved understanding about the role of metabolomic and inflammatory pathways in aging-related diseases, particularly diseases associated with impairment in rest-activity rhythms in older populations. Specifically, we found that numerous metabolites and pathways were associated with alterations in rest-activity rhythms, such as higher variability, lower amplitude, and reduced overall rhythmicity. Previous studies have linked these alterations in rest-activity rhythms with numerous aging-related diseases, including cardiometabolic conditions and cognitive decline. Specifically, we round over 65 amino acids, lipids and carbohydrates from a wide range of biochemical pathways that were significantly associated with rest-activity variables, and the findings are consistent with a role of metabolic pathways serving as the underlying driving force of disease development among older adults with impaired rest-activity rhythms. Our study also explored the relationship between metabolomic and inflammatory markers in relation to CVD, and the results also suggested multiple biological pathways that may be involved in cardiovascular impairment in older populations.

Our findings expanded the current knowledge about the relationship between circadian-regulated diurnal behaviors, human metabolism, and cardiovascular health. The findings reinforced the critical role of circadian function in health and diseases, and provided new evidence regarding mechanistic pathways that may mediate the adverse effects of circadian disruptions. Our findings also point to ample future directions for further research. With the availability of genomic, transcriptomic, epigenomic, and microbiome data, there is potential for multi-omics integration for further validation of our hypotheses regarding the molecular processes implicated in circadian rhythms. Moreover, novel statistical approaches could be harnessed to further elucidate the relationships among rest-activity rhythms, metabolomic profiles and disease risk, which may help identifying intermediate targets for developing disease therapies and developing models for disease risk prediction and management.

This research experience has been pivotal in my development as a physician–scientist. It strengthened my skills in framing research questions, critically evaluating outcomes, and identifying logical next steps. It also reinforced the value of multidisciplinary mentorship. Most importantly, it has cemented my commitment to advancing a career at the intersection of Otolaryngology and Sleep Medicine. As a newly minted Otolaryngology–Head and Neck Surgery resident, I plan to continue pursuing research opportunities that build on this work and ultimately translate into improved care for patients with sinonasal and sleep disorders.