Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The intertissue communication between the hypothalamus and adipose tissue for mammalian aging and longevity control

Award Number: U01AG086196
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

Group Awards By:

View Award Description

The intertissue communication between the hypothalamus and adipose tissue for mammalian aging and longevity control - ABSTRACT Recent studies in model organisms have demonstrated that the intertissue communications play a critical role in the regulation of aging and longevity. In mammals, we have demonstrated that the intertissue communication between the hypothalamus and adipose tissue, particularly mediated by extracellular vesicles-contained extracellular nicotinamide phosphoribosyltrasferase (eNAMPT), the rate-limiting NAD+ biosynthetic enzyme in mammals, functions to counteract age-associated physiological decline and promote longevity in mice. Most recently, we have demonstrated that Ppp1r17-positive neurons in the dorsomedial hypothalamus (DMHPpp1r17 neurons) regulate white adipose tissue (WAT) function, including lipolysis and eNAMPT secretion, through the sympathetic nervous system (SNS), and the feedback loop between DMHPpp1r17 neurons and WAT plays a critical role in the regulation of aging and longevity in mice. Our preliminary results suggest that this critical feedback loop between DMHPpp1r17 neurons and WAT wanes over age, which is one of the key triggers for aging. Indeed, chemogenetic stimulation of DMHPpp1r17 neurons in aged mice significantly ameliorates multiple aging phenotypes, decreases age-associated mortality rate, and extends longevity. However, why and how this critical feedback loop wanes over age remains unknown. In this research proposal, we hypothesize that adipose tissue starts decreasing adipose-resident immune cells, particularly type 2 innate lymphoid cells (ILC2s), and increases cellular senescence, causing WAT dysfunction and decreasing the content and the secretion of adipose EVs. Such WAT dysfunction then affects the regulation of Ppp1r17 function in DMHPpp1r17 neurons, affecting their function and accelerating WAT dysfunction through decreased SNS function. Maintaining this hypothalamus- WAT feedback loop is critical to counteract age-associated physiological decline and promote lifespan in mammals. To address this hypothesis, we propose the following three SPECIFIC AIMs: SPECIFIC AIM (1) will examine the effect of miR-20a, a microRNA species in adipose EVs, on the expression of Prkg1 in DMHPpp1r17 neurons during aging. SPECIFIC AIM (2) will elucidate how adipose immune cells are dysregulated during aging. We will particularly focus on ILC2s, which are dramatically reduced in adipose tissue during aging. SPECIFIC AIM (3) will address whether restoring ILC2 function by transplanting young ILC2s could delay aging and extend lifespan in mice. The anticipated outcome of the proposed research will advance our understanding of the importance of intertissue communications in mammalian aging and longevity control and open a new opportunity to develop an effective anti-aging intervention based on the intertissue communication between the hypothalamus and WAT.


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 = $609,383 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Aging Research	000	3	2/27/2026	NON-COMPETING CONTINUATION	$609,383
														Subtotal = $609,383

Issue Date FY: 2025 ( Subtotal = $597,195 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Aging Research	001	2	6/17/2025	NON-COMPETING CONTINUATION	$48,751
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Aging Research	000	2	4/2/2025	NON-COMPETING CONTINUATION	$548,444
														Subtotal = $597,195

Issue Date FY: 2024 ( Subtotal = $622,000 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Aging Research	000	1	5/21/2024	NEW	$622,000
														Subtotal = $622,000

Grand Total All Awards = $1,828,578

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The intertissue communication between the hypothalamus and adipose tissue for mammalian aging and longevity control

Award Number: U01AG086196

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 06/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer