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Investigating the role of maternal metabolic reprogramming in progeny physiology and aging

Award Number: R01AG067604
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Investigating the role of maternal metabolic reprogramming in progeny physiology and aging - Abstract Metabolic dysfunction is one of the major factors that impact lifespan in all systems. Mitochondrial defects are known to contribute to tissue dysfunction during aging. Alterations in carbohydrate metabolism, lipid oxidation, and redox metabolism have all been shown to play significant roles in many processes that can help dictate lifespan. One major factor that can dictate human lifespan and aging is the onset of metabolic syndrome. Over the past 30 years there has been a dramatic rise in the prevalence of metabolic disease and currently 1/3 of people world-wide suffer from metabolic syndrome. While genetics, environment, and nutrition play important roles in metabolic disfunction and lifespan, many recent studies have shown that disruptions in maternal metabolism can have a profound impact on progeny physiology and aging. While many studies have examined chromatin state and small RNAs to explain the heritability that maternal metabolism has on progeny disease these studies, in fact, support the idea that other factors contribute to the heritability of metabolic syndrome. Unlike sperm, that only contribute DNA to the early embryo, the oocyte provides a complex stockpile of metabolites, stored nutrients, and mitochondria to the progeny. Our research exploits the Drosophila oogenesis system as a tool to isolate large amounts of staged oocytes and embryos to conduct in-depth biochemical and metabolomics studies of the mechanisms that regulate oocyte physiology and metabolism. These tools combined with the speed and power of Drosophila genetics allow us to identify and characterize biochemical mechanisms in the oocyte that impact progeny metabolism. In this proposal we will examine how changes in systemic metabolism in aged mothers impact the reprogramming of progeny physiology and metabolism. In addition, we will examine whether reprogrammed progeny exhibit alterations to the metabolic shifts that occur normally during aging. We will test whether insulin-mediated changes in oocyte redox metabolism provides a signal that reprograms progeny physiology. We will also define the changes in chromatin landscape that underlie the transcriptional shift we observed in reprogrammed progeny. Our long-term goal is to use these studies to provide a mechanistic platform to study metabolic reprogramming in other systems, such as mice and mammalian cell models, and how it impacts progeny physiology and aging. Overall, this proposal challenges the dogmatic ideas we all have about the heritability of disease and explores the novel concept that changes in oocyte metabolism can reprogram progeny physiology and metabolism during aging.


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 = $0 )
2026	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Aging Research	000	5	12/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $432,173 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Aging Research	000	5	7/8/2024	NON-COMPETING CONTINUATION	$432,173
														Subtotal = $432,173

Issue Date FY: 2023 ( Subtotal = $432,173 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Aging Research	000	4	7/7/2023	NON-COMPETING CONTINUATION	$432,173
														Subtotal = $432,173

Issue Date FY: 2022 ( Subtotal = $432,173 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Aging Research	000	3	7/14/2022	NON-COMPETING CONTINUATION	$432,173
														Subtotal = $432,173

Issue Date FY: 2021 ( Subtotal = $431,953 )
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Aging Research	000	2	7/8/2021	NON-COMPETING CONTINUATION	$431,953
														Subtotal = $431,953

Issue Date FY: 2020 ( Subtotal = $428,174 )
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Aging Research	000	1	9/18/2020	NEW	$428,174
														Subtotal = $428,174

Grand Total All Awards = $2,156,646

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Investigating the role of maternal metabolic reprogramming in progeny physiology and aging

Award Number: R01AG067604

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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