Wednesday, October 1, 2025 10/1/2025

Single nuclei RNA-sequencing to map adipose cellular populations and senescent cells in older subjects

Award Number: R01AG075684
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

Single nuclei RNA-sequencing to map adipose cellular populations and senescent cells in older subjects - Aging is characterized by an expansion in adipose tissue (i.e. obesity), which plays a key role in the pathophysiology of many aging-diseases, including type 2 diabetes, atherosclerotic vascular disease, Alzheimer’s disease, and some cancers. Adipose tissue is composed of adipocytes, immune cells, endothelial cells, stem/stromal cells, and previously uncharacterized cellular populations. Adipose tissue also contains cells that have undergone cellular senescence, a state characterized by the arrest of the cell cycle and a senescence-associated secretory phenotype (SASP), which induces inflammation, cytotoxicity, and metabolic dysfunction in other cells and tissues. Recent research suggests that aging is associated with changes in adipose cellular populations and subpopulations, and that these variations may be involved in the biology of aging and etiology of aging-related diseases. Yet, the precise profiling of adipose tissue cellular composition has been limited due to a lack of robust cell surface markers for the numerous cellular subpopulations. Single-cell (sc) RNA seq is a novel high-resolution methodology that enables global identification of cellular populations and subpopulations (known and newly identified) in tissues. We have developed a single nuclei (sn)RNA-seq based method (a variation of scRNA-seq) that allows excellent identification, separation and clustering of adipose cellular populations, including mature adipocytes, immune cells, endothelial cells, and mesenchymal stem cells. Although snRNA-seq also is a promising tool for identification and characterization of cells undergoing senescence, it has not been used to more fully elucidate the importance of such cells in the biology of aging and the etiology of aging-related metabolic diseases. In Aim 1 we will conduct adipose tissue molecular profiling via snRNA-seq in three cohorts at baseline: younger lean, older lean, and older obese individuals. We will develop molecular atlases in these subjects to test the hypothesis that both aging and aging plus obesity will have distinct adipose tissue molecular profiles. In a subgroup of older obese subjects we will also test whether a lifestyle intervention changes the global molecular profile in adipose tissue to a profile closer to that in younger and older lean individuals. In Aim 2 we will focus on the identification, quantification, and functional characterization of adipose tissue senescent cells. Sub Aim 2A will test the hypotheses that the amount and function (i.e. SASP) of adipose tissue senescent cells will be elevated with aging and further enhanced by obesity, and that the lifestyle intervention (from Aim 1) will reduce senescent cell burden in older obese subjects. In Sub Aim 2B we will administer senolytic agents to a subgroup of older obese subjects (from Aim 1) to determine whether clearance of senescent cells improves metabolic outcomes. This Sub Aim will directly test the cellular senescence theory and will serve as a positive control for the lifestyle intervention regarding its potential anti-senescence effect.


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: 2025 ( Subtotal = $671,004 )
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	001	4	6/9/2025	NON-COMPETING CONTINUATION	$54,777
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	000	4	3/7/2025	NON-COMPETING CONTINUATION	$616,227
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	002	4	7/7/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $671,004

Issue Date FY: 2024 ( Subtotal = $684,697 )
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	003	3	4/18/2024	NON-COMPETING CONTINUATION	$684,697
2024	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	002	2	3/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$568,532
2024	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	000	2	11/17/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	001	1	3/18/2024	NEW	-$568,532
														Subtotal = $684,697

Issue Date FY: 2023 ( Subtotal = $684,697 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Aging Research	001	2	4/14/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$684,697
2023	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	000	1	4/14/2023	NEW	$0
														Subtotal = $684,697

Issue Date FY: 2022 ( Subtotal = $632,419 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Aging Research	000	1	6/9/2022	NEW	$632,419
														Subtotal = $632,419

Grand Total All Awards = $2,672,817

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Single nuclei RNA-sequencing to map adipose cellular populations and senescent cells in older subjects

Award Number: R01AG075684

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/15/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer