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C. Elegans as a Model of Cell Senescence and Alzheimer's Disease

Award Number: R21AG067147
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: 04/30/2024

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C. Elegans as a Model of Cell Senescence and Alzheimer's Disease - PROJECT SUMMARY/ABSTRACT Significance: Cell senescence is implicated in many age-related diseases. Drugs which postpone or reverse cellular senescence (SENO drugs) have been developed and three of these drugs are in human clinical trials. The availability of an inexpensive, whole-animal model of SENO drug action will accelerate development of new treatments of Alzheimer’s Disease. Background: SENO drugs ameliorate numerous age-related pathologies through a common pharmacological action: the selective killing or alteration of senescent cells. SENO drugs are expected to postpone diverse causes of human mortality including Parkinson’s Disease, Alzheimer’s Disease, and atherosclerosis, as well as cancer metastasis and recurrence. We propose to study SENO drugs, targeting three distinct pathways. These pathways lead to alternative responses characterized by distinct levels of AMP Kinase and P53. C. elegans transgenic strains have been engineered to express the amyloidogenic human proteins amyloid-beta (Aβ) and tau. We found that treatment with a SENO drug (piperlongumine) resulted in longer life in the wild-type and postponed paralysis in Aβ-expressing transgenic worm strains, and have since found a similar effect with a second SENO drug (KU60019). We propose to extend these studies by applying a representative set of five SENO drugs to wild-type nematodes and then apply single-cell RNA-Seq, to search for common seno-drug-driven transcriptional changes within and between specific cell types. 6


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: 2024 ( Subtotal = -$19 )
2024	2021	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Aging Research	001	2	8/19/2024	SUPPLEMENT FOR EXPANSION	-$8
2024	2021	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Aging Research	000	2	8/19/2024	NON-COMPETING CONTINUATION	-$11
														Subtotal = -$19

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Aging Research	000	2	4/10/2023	NON-COMPETING CONTINUATION	$0
2023	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Aging Research	001	2	4/11/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $336,150 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Aging Research	001	2	8/10/2021	SUPPLEMENT FOR EXPANSION	$143,650
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Aging Research	000	2	4/28/2021	NON-COMPETING CONTINUATION	$192,500
														Subtotal = $336,150

Issue Date FY: 2020 ( Subtotal = $231,000 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Aging Research	000	1	9/11/2020	NEW	$231,000
														Subtotal = $231,000

Grand Total All Awards = $567,131

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C. Elegans as a Model of Cell Senescence and Alzheimer's Disease

Award Number: R21AG067147

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: 04/30/2024

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