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Role of Hypothalamic IKK-beta/NF-kappaB in Nutritional Control of Aging

Award Number: R01AG031774
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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DESCRIPTION (provided by applicant): Aging is not only an important biological phenomenon but a core basis in many deleterious aging-related diseases. Having appreciated that IKKb/NF-kB-dependent inflammation mediates hypothalamic mechanism of aging, the long-term objective of this research is to study the involved neural types and molecular cascades, in order to develop strategies for treating aging-related diseases. In preliminary studies, hypothalamic astroglia have been targeted, using mouse models of astroglia-specific IKKb/NF-kB activation or inhibition. Preliminary data have demonstrated IKKb/NF-kB activation or inhibition in hypothalamic astroglia was sufficient to lead to aging acceleration or retardation, respectively. Hence, supported by these data, the hypothesis of this project is that astroglial IKKb/NF-kB is activated during early aging to induce neuronal inflammation and thus mediates the hypothalamic mechanism of aging. This hypothesis predicts that astroglial IKKb/NF-kB inhibition can reduce aging-related hypothalamic neuronal inflammation and therefore provide anti-aging effects. This hypothesis will be examined in 3 Aims: (1) Study the role of astroglial IKKb/NF-kB in aging-related hypothalamic inflammation; (2) Study the role of brain or hypothalamic astroglial IKKb/NF-kB in aging physiology and lifespan; (3) Study the neuronal mechanism in astroglial IKKb/NF-kB -mediated aging development. Experiments in these Aims will be carried out by using mouse models of site- and cell type-specific IKKb/NF-kB activation or inhibition. A list of molecular methods will be used to analyze astroglial and neuronal inflammatory changes as well as the inhibitory impacts on anti-aging molecular markers such as SIRTs and FOXOs. Also, a battery of physiological and histological approaches will be used to analyze aging of mouse models. Overall, successful completion of this project can yield new insights into the hypothalamic mechanism of aging, and enlighten a potential of targeting the hypothalamus for managing healthy aging and counteracting deadly aging-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: 2024 ( Subtotal = $579,289 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	000	14	6/4/2024	NON-COMPETING CONTINUATION	$579,289
														Subtotal = $579,289

Issue Date FY: 2023 ( Subtotal = $572,233 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	000	13	8/24/2023	COMPETING CONTINUATION	$572,233
														Subtotal = $572,233

Issue Date FY: 2022 ( Subtotal = -$418 )
2022	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	000	12	5/13/2022	NON-COMPETING CONTINUATION	-$418
														Subtotal = -$418

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	000	12	1/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $488,188 )
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	000	12	12/28/2018	NON-COMPETING CONTINUATION	$488,188
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	007	11	7/22/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$13,136
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	003	11	3/15/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$154,061
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	005	12	3/23/2019	NON-COMPETING CONTINUATION	$0
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	004	12	3/19/2019	NON-COMPETING CONTINUATION	$488,188
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	001	12	2/21/2019	NON-COMPETING CONTINUATION	-$488,188
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	002	10	3/14/2019	NON-COMPETING CONTINUATION	-$154,061
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	006	10	7/22/2019	NON-COMPETING CONTINUATION	-$13,136
														Subtotal = $488,188

Issue Date FY: 2018 ( Subtotal = $488,188 )
2018	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	000	10	1/23/2018	NON-COMPETING CONTINUATION	$439,368
2018	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	001	10	4/19/2018	NON-COMPETING CONTINUATION	$48,820
														Subtotal = $488,188

Issue Date FY: 2017 ( Subtotal = $488,188 )
2017	2017	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	001	9	6/15/2017	NON-COMPETING CONTINUATION	$48,820
2017	2017	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Aging Research	000	9	12/23/2016	NON-COMPETING CONTINUATION	$439,368
														Subtotal = $488,188

Issue Date FY: 2016 ( Subtotal = $488,188 )
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Aging Research	000	8	1/29/2016	NON-COMPETING CONTINUATION	$488,188
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	002	6	2/23/2016	COMPETING CONTINUATION	$64,630
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Aging Research	001	7	2/22/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$64,630
														Subtotal = $488,188

Issue Date FY: 2015 ( Subtotal = $488,188 )
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Aging Research	002	7	9/22/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$402,014
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	000	6	1/9/2015	COMPETING CONTINUATION	$488,188
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	001	6	9/21/2015	COMPETING CONTINUATION	-$402,014
														Subtotal = $488,188

Issue Date FY: 2014 ( Subtotal = $327,096 )
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	000	5	1/23/2014	NON-COMPETING CONTINUATION	$294,386
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	001	5	2/19/2014	NON-COMPETING CONTINUATION	$32,710
														Subtotal = $327,096

Issue Date FY: 2013 ( Subtotal = $309,105 )
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	000	4	1/15/2013	NON-COMPETING CONTINUATION	$294,386
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	001	4	5/17/2013	NON-COMPETING CONTINUATION	$14,719
														Subtotal = $309,105

Issue Date FY: 2012 ( Subtotal = $327,096 )
2012	2012	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	000	3	2/8/2012	NON-COMPETING CONTINUATION	$327,096
														Subtotal = $327,096

Issue Date FY: 2011 ( Subtotal = $327,096 )
2011	2011	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	001	2	6/21/2011	NON-COMPETING CONTINUATION	$20,826
2011	2011	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	000	2	2/2/2011	NON-COMPETING CONTINUATION	$306,270
														Subtotal = $327,096

Issue Date FY: 2010 ( Subtotal = $340,300 )
2010	2010	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Aging Research	000	1	1/29/2010	NEW	$340,300
														Subtotal = $340,300

Grand Total All Awards = $5,222,737

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Role of Hypothalamic IKK-beta/NF-kappaB in Nutritional Control of Aging

Award Number: R01AG031774

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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