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

Dual transcriptional programs coordinate lipogenic and membrane stress responsive programs in C. elegans

Award Number: R01AG068670
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

Group Awards By:

View Award Description

Dual transcriptional programs coordinate lipogenic and membrane stress responsive programs in C. elegans - Metabolism can affect the aging process through many mechanisms. The effects of calorie levels and the sensation of nutrient sources are powerful regulators. Other metabolic pathways may affect aging by acting as signaling or transcriptional regulators. The 1 carbon cycle has multiple links to aging, particularly through the production of the methyl donor S-adenosylmethionine (SAM). SAM is critical for epigenetic modification, which can affect many cellular processes, including aging. SAM is also important for the production of a phospholipid, phosphatidylcholine (PC), which is a major membrane component. We propose to study how one 1CC metabolite, PC, impacts aging though it’s role in a membrane stress pathway. Using a long-lived C. elegans model (sams-1) and human cell-based assays, we found that lowering PC induces a stress response in the Golgi, limiting the GTPase ARF-1.2/ARF1, which is a critical regulator of Golgi function. One effect of this stress response is the maturation of a membrane-intrinsic transcription factor, SBP-1/SREBP-1, to restore lipid homeostasis. We also found that a compensatory program is upregulated that produces an alternative ARF, arf- 1.1. to support Golgi function. We have identified at least one transcription factor, LET-607, which is also intrinsic to the membrane, as a regulator of this process. Thus, the Golgi stress response has multiple transcriptional outputs that play specific roles in correcting organelle misfunction. Finally, Golgi stress may be important in multiple neurodegenerative diseases, suggesting our studies could have a broad impact outside the aging field. Our proposal is based on data from multiple genetic screens, metabolomic studies, and other unbiased approaches. Next, our plan is to use a combination of cell biology, genetics and biochemistry several key questions. First, we will explore the basic cell biology of the Golgi stress response, which is not well understood. Second, we will determine how the LET-607 transcription factor is regulated during the stress response. These experiments will be complemented by our investigation on the molecular and biochemical basis explaining how ARF-1.1 can function when membrane conditions limit ARF-1.2. Finally, we have found that ARF-1.2 selectively disappears from the intestine in aging C. elegans. Because regulation of yolk secretion has important connections to aging, it is important to understand what regulates this loss of ARF-1.2 and how it might impact aging in sams-1 animals. Metabolites such as SAM and PC may have distinct roles in aging and stress in a variety of contexts, as these molecules can contribute to a variety of different processes. By delineating molecular mechanisms downstream of SAM and PC that affect membrane properties, we will uncover how specific aspects of 1 carbon and lipid metabolism drive changes in aging and stress.


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 = -$2,201 )
2026	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	5	4/15/2026	NON-COMPETING CONTINUATION	-$2,201
														Subtotal = -$2,201

Issue Date FY: 2025 ( Subtotal = $421,904 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	5	7/16/2025	NON-COMPETING CONTINUATION	$34,441
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	5	1/10/2025	NON-COMPETING CONTINUATION	$387,463
														Subtotal = $421,904

Issue Date FY: 2024 ( Subtotal = $430,514 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	4	6/10/2024	NON-COMPETING CONTINUATION	$43,051
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	4	2/7/2024	NON-COMPETING CONTINUATION	$387,463
														Subtotal = $430,514

Issue Date FY: 2023 ( Subtotal = $598,014 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	002	3	2/23/2023	NON-COMPETING CONTINUATION	$430,514
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	003	3	6/9/2023	SUPPLEMENT FOR EXPANSION	$167,500
2023	2021	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	1	12/29/2022	NEW	$202,643
2023	2021	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	1	11/16/2022	NEW	-$202,643
														Subtotal = $598,014

Issue Date FY: 2022 ( Subtotal = $227,872 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	2	6/13/2022	NON-COMPETING CONTINUATION	$43,055
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	2	2/14/2022	NON-COMPETING CONTINUATION	$184,817
														Subtotal = $227,872

Issue Date FY: 2021 ( Subtotal = $651,263 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	1	7/14/2021	NEW	$202,643
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	1	3/22/2021	NEW	$448,620
														Subtotal = $651,263

Grand Total All Awards = $2,327,365

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Dual transcriptional programs coordinate lipogenic and membrane stress responsive programs in C. elegans

Award Number: R01AG068670

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer