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Immunometabolic regulation of bone inflammaging

Award Number: R01AG076782
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Immunometabolic regulation of bone inflammaging - PROJECT SUMMARY Age-related inflammation and accumulation of ectopic lipid in multiple organs in elderly is associated with bone loss, frailty and chronic diseases. For example, bone and thymus are the major primary lymphoid organs that progressively accumulate ectopic lipid and adipocytes in humans and mouse models. The sympathetic nervous system (SNS) regulates all organ systems by localized release of catecholamines from post-synaptic vesicles in a rapid fashion without the time-lag required to complete events that control transcriptional activation or post-translational regulation of specific cytokines or adipokines. The catecholamines released from SNS in various local tissue niches is required for fatty acid oxidation, a process that is impaired in elderly. The key questions this proposal aims to address is: A) How does aging cause accumulation of ectopic lipid in bone marrow? B) Whether increase in ectopic lipid serves as an associative trigger for increase in bone inflammation and osteoporosis seen during aging. C) Can one prevent bone loss and ectopic accumulation in aging by targeting the mechanisms that link immune-metabolic crosstalk? These questions emanate from our discovery that aging is associated with increased degradation of norepinephrine (NE) due to elevated expression of Monoamine Oxidase A (MAOA), a catecholamine degradation enzyme. The long-term goal of this project is to decipher neuro-immune crosstalk that controls bone inflammation and to target this mechanism to develop new approaches to maintain or enhance bone function in elderly.


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: 2026 ( Subtotal = $479,676 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	5	3/9/2026	NON-COMPETING CONTINUATION	$479,676
														Subtotal = $479,676

Issue Date FY: 2025 ( Subtotal = $433,969 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	001	4	6/18/2025	NON-COMPETING CONTINUATION	$35,426
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	4	3/12/2025	NON-COMPETING CONTINUATION	$398,543
														Subtotal = $433,969

Issue Date FY: 2024 ( Subtotal = $452,354 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	3	4/17/2024	NON-COMPETING CONTINUATION	$452,354
														Subtotal = $452,354

Issue Date FY: 2023 ( Subtotal = $461,605 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	2	4/5/2023	NON-COMPETING CONTINUATION	$461,605
														Subtotal = $461,605

Issue Date FY: 2022 ( Subtotal = $502,500 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	1	6/9/2022	NEW	$502,500
														Subtotal = $502,500

Grand Total All Awards = $2,330,104

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Immunometabolic regulation of bone inflammaging

Award Number: R01AG076782

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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