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PESC3 The Heterogeneity of Vulnerabilities in Aging (HVAC) Cohort:
A new resource for early biomarker discovery and validation
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22-326S-1
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PESC3 The Heterogeneity of Vulnerabilities in Aging (HVAC) Cohort:
A new resource for early biomarker discovery and validation
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Dr. George Kuchel
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This research is being done to help better understand the role of specific biological hallmarks of aging in frailty and late life vulnerability and how they correlate with successful aging, frailty and sarcopenic obesity, a medical condition which is defined as the presence of both sarcopenia (loss of muscle) and obesity. The goals of this pilot project are to provide: (1) junior faculty interested in human subject research involving older adults with experience in the preparation of an IRB protocol, recruitment of human subjects and frailty assessments; (2) provide investigators interested in translational aging research with the opportunity to generate early stage feasibility and preliminary human data that could then be used in future NIH grant applications. This will be accomplished by studying healthy aging in a group of healthy older adults, as well as two different well-defined geriatric clinical phenotypes known to be associated with particular types of vulnerability or frailty. In order to achieve the objectives, we propose the following aims: In Aim 1, Dr. Earp and Dr. Kwon, both assistant professors with training and experience in exercise physiology (Kinesiology), as well as career interests in aging research, will recruit and perform baseline assessments following training by OAIC staff. In Aim 2, studies requiring fresh human peripheral blood cells will be carried out. RC3 will provide technical assistance with regards to carrying out the proposed studies and RC2 will provide assistance with statistical analysis of the results. Dr. Kwon, a kinesiologist who studies how age-related oxidative stress and mitochondrial dysfunction impact cell function, will assess metabolism, mitochondrial-derived reactive oxygen species autophagy and mitophagy in PBMC subpopulations (monocytes, B cells, CD4 and CD8 T cells) from each cohort by flow cytometry; Dr. Fan, an immunologist who studies integrin activation and leukocyte recruitment, will assess changes in neutrophil migration in each cohort using microscopy-based techniques. These studies will address important questions about heterogeneity with regards to the ex vivo function of peripheral blood cells in the four cohorts. In Aim 3, studies employing cryopreserved human peripheral blood cells from the four cohorts will be carried out. Dr. Bartley, an immunologist who studies how aging impacts the function of human T cells, will assess cellular metabolic changes in peripheral blood CD4 and CD8 T cells from each cohort using a Seahorse metabolic analyzer. She will also work with Dr. Li to assess metabolomics in the plasma from each subject. Dr. Xu, a gerontologist who studies senescence, will examine cellular senescence by enumerating p16 and p21 expression in CD3 + T cells previously isolated from PBMCs. The results from this analysis are important for our understanding of how the presence of senescent cells correlates with successful or unsuccessful aging. Finally, Dr. Ucar, a systems immunologist who studies how aging impacts transcriptomics, will use single cell RNAseq (scRNAseq) to further understand differences in PBMC from the four cohorts. The results from this analysis will help us to understand how gene expression correlates with successful aging, frailty and sarcopenic obesity.
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Aging
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Check with study contact
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Heather McAbee-Sevick. Telephone: 860-679-6115. Email: mcabeesevick@uchc.edu
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Enrolling/recruiting. For current recruitment status, please check with study contact.
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