# METTL3 in regulation of the aging process

> **NIH NIH R01** · BROWN UNIVERSITY · 2024 · $534,242

## Abstract

PROJECT SUMMARY
Aging is a complex process where perturbation of multiple molecular pathways contributes to organ
deterioration and aging-related morbidity and mortality. One component of the aging process is severe
dysregulation of gene expression that contributes to changes in the proteome of aged cells, which can
compromise cell function. Understanding the mechanisms responsible for aging-induced perturbation of gene
expression will be key to develop the necessary medical therapies. Although significant progress has been
made in understanding the transcriptional changes occurring with aging, very little is known about how post-
transcriptional events, such as RNA modifications, control protein synthesis during aging. In this proposal we
will examine the role of METTL3-mediated m6A mRNA methylation in the context of aging using muscle aging
as a model system. We hypothesize that METTL3-dependent mRNA methylation regulates the process of
aging by controlling the translation of specific pro-hypertrophic mRNAs. For the first time, utilizing gain- and
loss-of-function approaches we will characterize this novel regulatory program by establishing the molecular
mechanisms by which m6A regulates the life of select mRNAs and assess the global aging- and METTL3-
dependent translation dynamics (aim 1), examining the therapeutic benefit of enhancing m6A content to
counteract sarcopenia in clinically relevant animal models (aim 2), and define the role of m6A binding proteins
in muscle aging (aim 3). Completion of the proposed aims will allow the uncovering of a novel mechanism
responsible for post-transcriptional regulation of aging with significant therapeutics ramifications.

## Key facts

- **NIH application ID:** 10892860
- **Project number:** 5R01AG079842-03
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Federica Accornero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $534,242
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892860

## Citation

> US National Institutes of Health, RePORTER application 10892860, METTL3 in regulation of the aging process (5R01AG079842-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10892860. Licensed CC0.

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