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Mechanistic Approach to Preventing Atrophy and Restoring Function in Older Adults

Award Number: R01AG046401
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2014
PERIOD OF PERFORMANCE END DATE: 05/31/2020

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Mechanistic Approach to Preventing Atrophy and Restoring Function in Older Adults - DESCRIPTION (provided by applicant): As a function of our growing population of older adults, an estimated 3.48 million total knee arthroplasty (TKA) procedures will be performed annually in the U.S. by 2030. Despite the near-universal success of this surgery in mitigating chronic knee pain, TKA is not successful in restoring long-term physical function in older adults, primarily because of quadriceps muscle atrophy, which explains 77% of the strength deficits. Overall, strength and functional mobility in TKA patients is 30-50% below age-matched healthy controls. Functional tasks such as stair-climbing, which is considered a high fall-risk activity, remain a clinical problem for 75% of patients following TKA. Muscle atrophy occurs in both operative and non-operative legs, and is essentially permanent for older patients because their ability to increase muscle mass is significantly impaired. Thus, safe and effective treatments to prevent muscle loss and preserve strength are urgently needed and clinically meaningful, as they have the potential to significantly impact the quality of life for millions of older adults. Te purpose of the proposed clinical research is to determine the effects of essential amino acid (EAA) supplementation on muscle mass, strength, and functional mobility following TKA in older adults. Our hypothesis, based on strong preliminary data, is that twice-daily ingestion of 20 g of EAA for 1 wk before through 6 wk after TKA will increase basal rates of muscle protein synthesis via inactivation of catabolic signaling, and up-regulation of anabolic and cyto-protective proteins. We further hypothesize that short-term atrophy prevention and accelerated return of functional mobility will lead to longer-term structural and functional adaptations, and improved quality of life in older TKA patients vs. Placebo. The rationale for the proposed research is that effective treatments to prevent muscle atrophy after increasingly common TKA surgery will result in short- and longer-term muscle cell adaptations that boost functional mobilit and quality of life. Identifying the mechanisms up-regulated by EAA treatment that preserve muscle volume and mobility will have a major impact on rehabilitation science. The proposed research will empirically test our hypotheses by accomplishing two specific aims: (1) determine if EAA elevates basal rates of muscle protein synthesis by up- regulating anabolic pathways and cyto-protective proteins, and inactivating catabolic pathways in the short term (6 wk post-TKA) vs. Placebo and (2) determine if short-term prevention of atrophy, weakness, and functional mobility leads to positive changes in muscle cell structure and function, and improved quality of life (WOMAC & SF-36) in the longer term (6 mo and 1 yr post-TKA) vs. Placebo. The proposed work is significant because it advances knowledge of the molecular and cellular changes occurring during muscle atrophy (Placebo) and atrophy prevention (EAA) in a clinical setting using a treatment that is broadly applicable, is well tolerated, and can be implemented immediately.


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: 2021 ( Subtotal = $0 )
2021	2018	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	000	5	1/28/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	001	5	6/2/2020	NON-COMPETING CONTINUATION	$0
2020	2018	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	000	5	4/24/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $485,308 )
2018	2018	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	000	5	1/31/2018	NON-COMPETING CONTINUATION	$436,777
2018	2018	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	001	5	4/12/2018	NON-COMPETING CONTINUATION	$48,531
														Subtotal = $485,308

Issue Date FY: 2017 ( Subtotal = $522,477 )
2017	2017	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	000	4	3/1/2017	NON-COMPETING CONTINUATION	$391,171
2017	2017	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	003	4	6/19/2017	NON-COMPETING CONTINUATION	$43,462
2017	2017	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	004	4	9/8/2017	SUPPLEMENT FOR EXPANSION	$87,844
2017	2016	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Aging Research	002	3	3/21/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$281,786
2017	2015	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Aging Research	001	2	3/21/2017	NON-COMPETING CONTINUATION	-$281,786
														Subtotal = $522,477

Issue Date FY: 2016 ( Subtotal = $437,877 )
2016	2016	UNIVERSITY OF OREGON	POST OFFICE BOX 3237	EUGENE	OR	97403	LANE	USA	Aging Research	000	3	2/25/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$437,877
														Subtotal = $437,877

Issue Date FY: 2015 ( Subtotal = $457,601 )
2015	2015	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Aging Research	000	2	2/19/2015	NON-COMPETING CONTINUATION	$457,601
														Subtotal = $457,601

Issue Date FY: 2014 ( Subtotal = $560,537 )
2014	2014	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Aging Research	000	1	5/12/2014	NEW	$560,537
														Subtotal = $560,537

Grand Total All Awards = $2,463,800

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Mechanistic Approach to Preventing Atrophy and Restoring Function in Older Adults

Award Number: R01AG046401

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2014

PERIOD OF PERFORMANCE END DATE: 05/31/2020

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