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Womb to Tomb: Developmental Programming and Aging Interactions in Primates

Award Number: U19AG057758
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Womb to Tomb: Developmental Programming and Aging Interactions in Primates - ABSTRACT Specific aims/significance. In our well-characterized baboon nonhuman primate (NHP) models of developmental programming and aging we use both categorical group and longitudinal, life course approaches to evaluate interactive programming-aging mechanisms. Developmental programming can be defined as responses to challenges in critical developmental time windows that alter life course phenotype. Premises/hypotheses. 1. Aging antecedents are present early in the hippocampal-hypothalamo-pituitary- adrenal (HHPA) axis (HHPAA), brain, and behavior; cardiovascular system (CVS); and metabolism. 2. Programming-aging interactions are major determinants of life course HHPA, brain, behavior, CVS, and metabolic health span. 3. Comparing normative, life course observational control data with data from three interventions that alter aging trajectory provides insights into key aging mechanisms and cellular pathways and information needed for translation to humans to anticipate age-related mechanisms that either increase or decrease health span. Findings enable development of markers and beneficial interventions in human aging. Projects - 1. HHPAA, Brain, and Behavior. 2: CVS Function. 3: Metabolism. Cores - A: Administrative; B: Animal; C: Genomics; D: MRI; E: Samples and Data Management. Synergy: All components study all 96 animals with in vivo MRI and tether studies and in vitro histological, cell culture, and molecular approaches. We study 96 baboons in 4 groups, equal males and females at 6–17 years (y) (human equivalent ~18–68y; 24– 68% of the life course). Groups: 1. 48 normal life course controls (NLC); 2. 16 IUGR offspring (F1) of moderately undernourished mothers; 3. 16 F1 of obese, over-nourished mothers; 4. In 16 at 12–17y we clamp plasma cortisol to normal 5y levels. Comparison of aging mechanisms in NLC and interventions provides information on life course whole animal and cellular mechanisms modified by programming-aging interactions. New preliminary data. We present new evidence of increased cortisol and accelerated brain, CVS, and metabolic aging in IUGR. Responsiveness to PAR-16-143 Complex Integrated Multi-Component Projects in Aging Research (U19). We address requested “Large-scale longitudinal observational studies… integration of multiple outcomes with molecular, genetic, mechanistic data and interventions… animal models for aging- related conditions… multiple endpoints to elucidate mechanisms.” Investigators are from multiple institutions and have worked and published together in aging research and programming and in completing large NIH P01s, R24s, P51s. We share resources worldwide. Innovation. Life course NHP studies are rare. We assembled unique cohorts and built our own custom facility for these studies. We now 1. perform biopsies not euthanasia, enabling further applications on these cohorts; 2. combine U19 in vivo and in vitro data with histological and molecular data from our extensive fetal (130 fetuses) and postnatal archives (120 adults birth to 25y) to produce a new mechanistic programming and aging framework from womb to tomb.


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 = $70,468 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	003	6	8/15/2024	SUPPLEMENT FOR EXPANSION	$100,000
2024	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	6	2/14/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,017,750
2024	2022	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	000	5	2/14/2024	NON-COMPETING CONTINUATION	-$1,047,282
2024	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	002	6	5/31/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $70,468

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	000	5	4/18/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	001	5	8/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $2,552,738 )
2022	2022	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	001	5	9/5/2022	NON-COMPETING CONTINUATION	$2,552,738
2022	2021	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	000	4	5/9/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,552,738

Issue Date FY: 2021 ( Subtotal = $2,638,712 )
2021	2021	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	000	4	7/14/2021	NON-COMPETING CONTINUATION	$2,638,712
														Subtotal = $2,638,712

Issue Date FY: 2020 ( Subtotal = $2,289,346 )
2020	2020	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	004	3	7/7/2020	NON-COMPETING CONTINUATION	$0
2020	2020	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	003	3	6/24/2020	NON-COMPETING CONTINUATION	$2,657,007
2020	2019	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	000	2	11/26/2019	NON-COMPETING CONTINUATION	$0
2020	2019	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	002	2	12/9/2019	NON-COMPETING CONTINUATION	-$172,042
2020	2018	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	001	1	12/6/2019	NEW	-$195,619
														Subtotal = $2,289,346

Issue Date FY: 2019 ( Subtotal = $2,816,377 )
2019	2019	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	001	2	6/26/2019	NON-COMPETING CONTINUATION	$2,816,377
2019	2018	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	000	1	12/13/2018	NEW	$0
														Subtotal = $2,816,377

Issue Date FY: 2018 ( Subtotal = $2,874,315 )
2018	2018	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Aging Research	000	1	9/18/2018	NEW	$2,874,315
														Subtotal = $2,874,315

Grand Total All Awards = $13,241,956

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Womb to Tomb: Developmental Programming and Aging Interactions in Primates

Award Number: U19AG057758

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/30/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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