Tuesday, July 1, 2025 7/1/2025

Use of C. elegans as a model to study aging-associated neurodegeneration

Award Number: R01AG073994
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Use of C. elegans as a model to study aging-associated neurodegeneration - Aging can cause neurodegeneration and is also a major risk factor for neurodegenerative diseases. However, the molecular mechanisms underlying aging-associated neurodegeneration are not well understood yet. Therefore, our-long-term goal is to understand the molecular mechanisms undying neurodegeneration in aging and neurodegenerative diseases. The objective of this proposal is to use C. elegans as a model to uncover novel mechanisms underlying aging-associated neurodegeneration. This proposal builds on our recent punished work, in which we revealed that antimicrobial peptide (AMPs) released by epidermal cells in aged animals lead to neurodegeneration through activating a neuropeptide receptor (NPR). Importantly, our collaborators showed that signaling via the same molecular players (AMPs and NPR) also leads to neurite degeneration in rat cortical neurons, supporting the conclusion that the mechanisms identified in our system are preserved in mammalian neurons. Based on these exciting findings, we propose to use genetic and genomic methods to further examine the signals that cause the overexpression of AMPs in aged animals and to uncover the transcriptional regulators that lead to neurodegeneration upon aging. We believe that careful analysis of aging-associated neurodegeneration in C. elegans will reveal previously unknown but potentially conserved mechanisms that govern fundamental features of neurodegeneration in aging. This proposal will determine the function and regulation of AMPs in aging-associated neurodegeneration (Aim 1), and establish cell-autonomous mechanisms underlying neurodegeneration in aged animals (Aim 2). It is expected that completion of this proposal will lead to the discovery of novel mechanisms of aging-associated neurodegeneration, the establishment of C. elegans PVD neurons as a powerful model to study aging- associated neurodegeneration, and the generation of new tools for further studies. As many neurodegenerative disorders are associated with aging, our studies may lead to a better understanding of the pathogenesis of these diseases.


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 = $483,402 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	001	4	6/18/2025	NON-COMPETING CONTINUATION	$39,461
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	000	4	3/11/2025	NON-COMPETING CONTINUATION	$443,941
														Subtotal = $483,402

Issue Date FY: 2024 ( Subtotal = $493,267 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	001	3	6/28/2024	NON-COMPETING CONTINUATION	$49,326
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	000	3	3/4/2024	NON-COMPETING CONTINUATION	$443,941
														Subtotal = $493,267

Issue Date FY: 2023 ( Subtotal = $519,671 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	000	2	2/15/2023	NON-COMPETING CONTINUATION	$519,671
														Subtotal = $519,671

Issue Date FY: 2022 ( Subtotal = $776,073 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Aging Research	000	1	5/18/2022	NEW	$519,671
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Aging Research	001	1	9/22/2022	NEW	$256,402
														Subtotal = $776,073

Grand Total All Awards = $2,272,413

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Use of C. elegans as a model to study aging-associated neurodegeneration

Award Number: R01AG073994

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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