# Determining the role of ribosomal DNA in metazoan aging

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2020 · $39,975

## Abstract

ABSTRACT
Ribosomal RNA (rRNA) accounts for 80% of all cellular transcripts. rRNA is encoded by long tandem ribosomal
DNA repeats (rDNA). Differences in rDNA copy number associate with changes in transcriptome and
mitochondrial abundance, which suggests that rDNA copy number may have bearing on phenotype. Two
aspects of rDNA copy number – the number of genomic repeats, and the number of extrachromosomal repeats
– have been associated with aging. Specifically, a reduction of genomic rDNA repeats has been observed in
some aging mammalian tissues. Additionally, an increase in extrachromosomal circular rDNA (ecc-rDNA)
repeats occurs with yeast replicative age. Whether rDNA copy number itself influences aging phenotypes
remains unresolved. While reductions in genomic rDNA copy number with age have been reported in specific
post-mitotic mammalian tissues, it is unclear how prevalent this feature is, or by what mechanisms rDNA
copies may be lost in a multicellular eukaryote. Furthermore, age-associated increases in ecc-rDNA have been
extensively characterized in yeast but have been largely unexplored in metazoans. I propose to utilize
Caenorhabditis elegans as an aging model to determine 1) If rDNA copy number influences aging and 2) How
aging affects rDNA copy number. In Aim 1, I will assess lifespan, fertility, and length of development in two sets
of recombinant inbred lines (RILs). The first set of RILs, which I developed from a cross of a C. elegans wild
isolate and a derivative of the lab strain, were selected specifically for high (~420 copies) or low (~130 copies)
rDNA copy number. The second set of RILs, part of the C. elegans Multiparental Experimental Evolution
(CeMEE) panel, were developed from an advanced intercross of 16 wild isolates that underwent multiple
rounds of experimental evolution prior to RIL development. For both sets of RILs, I will perform genome-wide
association analyses to determine if rDNA copy number either additively or epistatically affects aging
phenotypes. In Aim 2, I will assess both genomic rDNA copy number and ecc-rDNA levels during aging in C.
elegans. Together these Aims will determine the relationship between rDNA and aging in a metazoan system,
including if rDNA copy number changes are a universal hallmark of aging.

## Key facts

- **NIH application ID:** 10057210
- **Project number:** 5F31AG063450-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Ashley Nicole Hall
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,975
- **Award type:** 5
- **Project period:** 2019-09-16 → 2021-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057210

## Citation

> US National Institutes of Health, RePORTER application 10057210, Determining the role of ribosomal DNA in metazoan aging (5F31AG063450-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057210. Licensed CC0.

---

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