Wednesday, December 17, 2025 12/17/2025

Lipid signaling in cellular senescence and tissue aging

Award Number: R01AG069865
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Lipid signaling in cellular senescence and tissue aging - Abstract This proposal is focused on the challenge of understanding and thus improving treatment for idiopathic pulmonary fibrosis, a devastating interstitial lung disease without effective treatments. Deregulation of lipid signaling and metabolism has long been studied in pulmonary fibrosis, pointing to changes in sphingolipid and ceramide pathways that may impact pathology. In recent years, increased attention has been paid to a possible role for senescent cells in the lung as a critical factor driving pulmonary fibrosis. Senescent cells express inflammatory factors, including signaling lipids, which may drive the fibrotic process. Current questions include why senescent cells accumulate in these patients and how their pro-inflammatory activity might be mitigated. An inference is that preventing formation of senescent cells, blocking their lipid signaling and/or promoting their clearance from the lung might prevent pulmonary fibrosis or block disease progression. Importantly, there may be a direct link between sphingolipid pathways and cellular senescence. Ceramides have been shown to induce senescence in otherwise proliferating cells. Our studies have implicated lipid peroxidation and its aldehyde end-products such as 4-hydroxynonenal as key mediators of accelerated senescence. Transcriptomic, proteomic and lipidomic analysis of proliferative and senescent lung cells will be used to identify key senescence factors and networks that may point to the specific lipid metabolic pathways that drive senescence and inflammatory signaling. We will then examine lipids and modulators for the ability to promote or prevent senescence. Finally, we will examine whether manipulation of lipid metabolic pathways can be used to potentiate clearance of senescent cells and thereby limit pulmonary fibrosis. With success in these studies, we anticipate identification of candidate therapeutics with potential to move to clinical trials.


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 = -$34,319 )
2026	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Aging Research	000	5	12/9/2025	NON-COMPETING CONTINUATION	-$34,319
														Subtotal = -$34,319

Issue Date FY: 2024 ( Subtotal = $352,994 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Aging Research	000	5	7/3/2024	NON-COMPETING CONTINUATION	$352,994
														Subtotal = $352,994

Issue Date FY: 2023 ( Subtotal = $352,994 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Aging Research	000	4	8/14/2023	NON-COMPETING CONTINUATION	$352,994
														Subtotal = $352,994

Issue Date FY: 2022 ( Subtotal = $352,994 )
2022	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Aging Research	000	3	7/18/2022	NON-COMPETING CONTINUATION	$352,994
														Subtotal = $352,994

Issue Date FY: 2021 ( Subtotal = $352,994 )
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Aging Research	000	2	8/24/2021	NON-COMPETING CONTINUATION	$352,994
														Subtotal = $352,994

Issue Date FY: 2020 ( Subtotal = $366,545 )
2020	2020	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Aging Research	000	1	9/14/2020	NEW	$366,545
														Subtotal = $366,545

Grand Total All Awards = $1,744,202

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Lipid signaling in cellular senescence and tissue aging

Award Number: R01AG069865

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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