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

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $432,173

## Abstract

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.

## Key facts

- **NIH application ID:** 10447719
- **Project number:** 5R01AG067604-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Matthew Sieber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $432,173
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447719

## Citation

> US National Institutes of Health, RePORTER application 10447719, Investigating the role of maternal metabolic reprogramming in progeny physiology and aging (5R01AG067604-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10447719. Licensed CC0.

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