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METTL3 in regulation of the aging process

Award Number: R01AG079842
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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METTL3 in regulation of the aging process - PROJECT SUMMARY Aging is a complex process where perturbation of multiple molecular pathways contributes to organ deterioration and aging-related morbidity and mortality. One component of the aging process is severe dysregulation of gene expression that contributes to changes in the proteome of aged cells, which can compromise cell function. Understanding the mechanisms responsible for aging-induced perturbation of gene expression will be key to develop the necessary medical therapies. Although significant progress has been made in understanding the transcriptional changes occurring with aging, very little is known about how post- transcriptional events, such as RNA modifications, control protein synthesis during aging. In this proposal we will examine the role of METTL3-mediated m6A mRNA methylation in the context of aging using muscle aging as a model system. We hypothesize that METTL3-dependent mRNA methylation regulates the process of aging by controlling the translation of specific pro-hypertrophic mRNAs. For the first time, utilizing gain- and loss-of-function approaches we will characterize this novel regulatory program by establishing the molecular mechanisms by which m6A regulates the life of select mRNAs and assess the global aging- and METTL3- dependent translation dynamics (aim 1), examining the therapeutic benefit of enhancing m6A content to counteract sarcopenia in clinically relevant animal models (aim 2), and define the role of m6A binding proteins in muscle aging (aim 3). Completion of the proposed aims will allow the uncovering of a novel mechanism responsible for post-transcriptional regulation of aging with significant therapeutics ramifications.


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 = $515,089 )
2025	2025	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	001	4	7/11/2025	NON-COMPETING CONTINUATION	$515,090
2025	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Aging Research	000	1	2/20/2025	NEW	-$1
														Subtotal = $515,089

Issue Date FY: 2024 ( Subtotal = $539,685 )
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	002	3	5/2/2024	NON-COMPETING CONTINUATION	$534,242
2024	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	001	2	1/3/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$539,216
2024	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Aging Research	000	1	1/2/2024	NEW	-$533,773
														Subtotal = $539,685

Issue Date FY: 2023 ( Subtotal = $533,774 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Aging Research	000	1	7/24/2023	NEW	$533,774
														Subtotal = $533,774

Grand Total All Awards = $1,588,548

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METTL3 in regulation of the aging process

Award Number: R01AG079842

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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