# Regulation of Mitochondrial Gene Expression and Function by GDF11 Signaling

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $367,975

## Abstract

PROJECT SUMMARY. Skeletal muscle is increasingly recognized as an endocrine tissue with the capacity to
regulate physiological homeostasis via the secretion of muscle-derived growth factors and cytokines known as
myokines. Although myokines may regulate aging in mammals, these studies are hampered by the relatively
long lifespan of mice. Over the past decades, shorter-lived organisms, such as the fruit fly Drosophila, have
proven instrumental in dissecting the endocrine signaling pathways that regulate aging. We have found that the
myokine Myoglianin (the homolog of human GDF11) regulates tissue aging and lifespan in Drosophila. GDF11
has been reported to delay aging in mice but the molecular and cellular mechanisms involved are largely
unknown. To investigate its action, my group has profiled the gene expression changes induced by
Myoglianin/GDF11-like signaling in muscle and found that it regulates the expression of many genes involved
in mitochondrial function and metabolism. Afterwards, we have computationally analyzed the promoter regions
of Myoglianin-regulated genes and identified transcription factor binding motifs that are enriched. With
subsequent functional studies, we have defined a set of transcription factors that act downstream of
Myoglianin/GDF11-like signaling and regulate mitochondrial gene expression. On the basis of these
preliminary data, my group now proposes to determine: 1) the mechanisms by which Myoglianin regulates
downstream transcription factors that promote mitochondrial gene expression; 2) the regulation of
mitochondrial function by Myoglianin during aging; and 3) the endocrine modulation of mitochondrial function in
non-muscle tissues such as the brain in response to muscle-derived Myoglianin. The successful completion of
this research will provide fundamental new insight into the mechanisms by which Myoglianin/GDF11-like
signaling delays aging and its possible roles in extending healthy lifespan in humans.

## Key facts

- **NIH application ID:** 10169211
- **Project number:** 5R01AG055532-05
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Fabio Demontis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,975
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169211

## Citation

> US National Institutes of Health, RePORTER application 10169211, Regulation of Mitochondrial Gene Expression and Function by GDF11 Signaling (5R01AG055532-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169211. Licensed CC0.

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