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Investigating Vulnerable Cell Populations in Aging-Induced Circadian Clock Remodeling and Disruption

Award Number: F30AG097071
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/03/2025
PERIOD OF PERFORMANCE END DATE: 09/02/2029

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Investigating Vulnerable Cell Populations in Aging-Induced Circadian Clock Remodeling and Disruption - Project Summary Disruption of circadian clocks—cell-intrinsic oscillators responsible for maintaining daily physiological and behavioral rhythms—is an emerging hallmark of aging. While studies have shown that circadian clock outputs remodel or diminish with age in various tissues, the specific cellular and molecular drivers of the bidirectional relationship between aging and the circadian clock remain unknown. This project seeks to identify key cell populations whose circadian rhythms are most impacted by aging and those that are most vulnerable to loss of the circadian clock, aiming to understand how aging affects circadian rhythms across cell types and how circadian disruption influences aging at cellular and molecular levels. The main approach centers around high-throughput single-nucleus RNA sequencing of flash-frozen tissues. In Specific Aim 1, I will profile sex-matched young and aged mice sampled every four hours over two days in constant darkness, dissecting seven organs: brain, liver, heart, kidney, lung, colon, and skeletal muscle. Clustering analyses will identify cell types, and circadian genes will be characterized using the JTK_Cycle algorithm, comparing results across sex and age. I will map circadian cell-cell interactions through ligand-receptor analysis to reveal age-related shifts in intercellular communication and perform transcription factor enrichment analysis to uncover upstream regulators in cell types showing pronounced changes with aging. In Specific Aim 2, I will perform single-nucleus sequencing on wild-type young and aged mice, Bmal1 knockout mice—a genetic model of circadian disruption—and aged mice exposed to chronic jet lag—an environmental model of circadian disruption. This analysis will identify cell populations vulnerable to circadian disruption and determine whether circadian disruption-induced early aging reflects natural aging or represents a distinct pathology. The outcomes of this study will enhance our understanding of the interplay between circadian rhythms and aging, offering a roadmap for examining the circadian output of cell types involved in aging-associated diseases such as Alzheimer's disease, Type II diabetes, major depressive disorder, and cardiovascular disease. By uncovering the circadian rhythms of disease-associated genes and receptors, the findings could inform therapeutic timing and improve chronotherapy by aligning drug delivery with the biological rhythms of specific cell types. With the mentorship of my sponsor, co-sponsor, thesis committee, and the support of this fellowship, I am confident I will be well-prepared to pursue this project and achieve my goal of becoming a physician-scientist and an independent investigator in the field of aging biology.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $55,114 )
2026	2026	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Aging Research	000	2	9/1/2026	NON-COMPETING CONTINUATION	$55,114
														Subtotal = $55,114

Issue Date FY: 2025 ( Subtotal = $54,538 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Aging Research	001	1	9/3/2025	NEW	$0
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Aging Research	000	1	9/3/2025	NEW	$54,538
														Subtotal = $54,538

Grand Total All Awards = $109,652

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Investigating Vulnerable Cell Populations in Aging-Induced Circadian Clock Remodeling and Disruption

Award Number: F30AG097071

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/03/2025

PERIOD OF PERFORMANCE END DATE: 09/02/2029

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