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The role of hyaluronan in age-related vascular and skeletal muscle dysfunction

Award Number: R00AT010017
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2018
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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The role of hyaluronan in age-related vascular and skeletal muscle dysfunction - PROJECT SUMMARY Candidate: Daniel Machin, PhD is a postdoctoral fellow in the Translational Physiology Laboratory at the University of Utah. Dr. Machin’s research is focused on the impact of high molecular weight hyaluronan (HMW- HA) dietary supplementation on the vascular and skeletal muscle function in advanced age. Dr. Machin’s long- term goal is to independently direct an extramurally funded laboratory with research focused on natural countermeasures to aging and age-related diseases. Career Development: This award will support Dr. Machin’s career development by building on his existing training in aging cardiovascular and exercise physiology. Specifically, Dr. Machin will receive extensive training in the planning and execution of studies assessing skeletal muscle mitochondrial function and hemodynamics in rodents. The career development plan outlines a coordinated effort to train the candidate in areas including: vascular biology of aging; assessment of skeletal muscle mitochondrial respiration, blood flow distribution, and microvascular oxygen perfusion; didactic course work designed to facilitate a better understanding of fundamentals of therapeutic product development, animal research, and biostatistics; and, regular attendance at vascular aging, nutrition, microcirculatory, and exercise physiology conferences. Environment: The University of Utah is an ideal environment for Dr. Machin’s career development. This environment provides all of the resources needed to complete the proposed studies during the K99 phase and allows for collaboration with experts in aging, vascular biology, and exercise physiology. The University of Utah also provides a rich environment for formal and informal training in career development. Research: The central hypothesis of this research project is that age-related reductions in HMW-HA result in a deteriorated glycocalyx that leads to micro/macrovascular dysfunction that impairs skeletal muscle hemodynamics, attenuating maximal exercise capacity. Furthermore, we hypothesize that chronic HMW-HA dietary supplementation can reverse age-related glycocalyx deterioration and micro/macrovascular dysfunction, as well as prevent the decline in maximal exercise capacity with advanced age. To test these hypotheses we will assess glycocalyx thickness, micro/macrovascular function, maximal exercise capacity, and skeletal muscle hemodynamics and mitochondrial function in young and old mice, as well as in inducible, endothelial HMW-HA synthase 2 (HAS2) knockout and control mice. To determine if there are any direct effects of HMW-HA on skeletal muscle, we will also assess exercise and skeletal muscle outcomes in inducible, skeletal muscle HAS2 knockout and control mice. The results from these studies will provide insight into the etiology of age-related vascular and skeletal muscle dysfunction and provide a proof of mechanism of action for HMW-HA in prevention of age-related 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 = -$1,073 )
2025	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Research and Training in Complementary and Integrative Health	000	5	11/26/2024	NON-COMPETING CONTINUATION	-$1,073
														Subtotal = -$1,073

Issue Date FY: 2022 ( Subtotal = $249,000 )
2022	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Research and Training in Complementary and Integrative Health	000	5	7/14/2022	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2021 ( Subtotal = $249,007 )
2021	2021	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Research and Training in Complementary and Integrative Health	002	4	7/9/2021	NON-COMPETING CONTINUATION	$249,000
2021	2020	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Research and Training in Complementary and Integrative Health	000	3	12/10/2020	EXTENSION WITH OR WITHOUT FUNDS	$0
2021	2020	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Research and Training in Complementary and Integrative Health	001	3	2/1/2021	EXTENSION WITH OR WITHOUT FUNDS	$7
														Subtotal = $249,007

Issue Date FY: 2020 ( Subtotal = $249,000 )
2020	2020	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Research and Training in Complementary and Integrative Health	000	3	7/20/2020	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $745,934

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The role of hyaluronan in age-related vascular and skeletal muscle dysfunction

Award Number: R00AT010017

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2018

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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