# Alternative splicing and expression of transposable elements in aging skeletal muscle

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2024 · $485,375

## Abstract

Project Summary/Abstract
Aging is associated with decline in skeletal muscle function even in healthy individuals, and the molecular
mechanisms underlying this aging process are incompletely understood. The overall goal of the proposed
project is to discover genomic alterations in skeletal muscle that are associated with aging, with the long term
goal of creating a better understanding of mechanisms of aging in order to help prevent or slow down the aging
related decline in muscle function. It is known that expression of hundreds of genes is altered in healthy
muscle aging, we will dissect the aging muscle transcriptome in two ways beyond gene expression. Alternative
splicing of messenger RNA creates diversity in the proteome and has been implicated in causing disease.
Additionally, alternative splicing can cause exonization of previously intronic sequences, potentially leading to
an amino acid sequence not previously seen by the immune system. Based on our preliminary data, Aim 1 will
explore if alternative splicing of mRNA results in quantitative differential isoform changes associated with
aging, resulting in increased expression of non-functional proteins that are relevant for healthy muscle function.
Moreover, we will predict protein changes from alternative splicing and the potential for generation of novel
peptide sequences. On the other hand, aging is associated with inflammatory changes (referred to as
“inflammaging”). In Aim 2, we will investigate a potential source of inflammaging by quantifying expression of
transposable elements in the aging muscle including LINE-1, HERV-K, and SINEs. All proposed analyses will
be conducted on two existing datasets, including RNA-sequencing data from muscle biopsies of healthy
individuals, which is ideal to isolate the effect of aging on the muscle transcriptome without influence from
diseases more common in older individuals. Additionally, we will validate our results in a much larger and less
selected RNA-sequencing data of hundreds of muscle biopsies, which will add confidence in the external
validity of our results.

## Key facts

- **NIH application ID:** 10994905
- **Project number:** 1R21AG087517-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Tomas M Mustelin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $485,375
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994905

## Citation

> US National Institutes of Health, RePORTER application 10994905, Alternative splicing and expression of transposable elements in aging skeletal muscle (1R21AG087517-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10994905. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*