# The Tunicate Ciona: A New Model for the Effects of Aging on Tissue Regeneration

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $334,400

## Abstract

Summary
 The loss of regenerative capacity during aging is a major unsolved problem in biology and biomedicine.
Here we continue to develop the tunicate Ciona intestinalis as a model for regenerative aging research. Ciona
has many favorable attributes for this purpose, including a small sequenced genome, an extensive tool kit for
genetic manipulations, a short life span, powerful regeneration capacities that disappear with age, an identified
stem cell niche involved in regeneration, a collection of stable transgenic lines with green fluorescent protein
expressed in specific tissues, and the ability to produce chimeric animals containing young and old body parts.
Most importantly, Ciona belongs to an invertebrate chordate group recognized as the closest living relative of
vertebrates, suggesting that research on this organism will be generally relevant to vertebrates, including
humans. The three specific aims of this proposal are designed to incrementally advance our understanding
the relative roles of the stem cell niche, the blastema, and the surrounding tissue environment in regenerative
aging and the molecular mechanisms governing this process using the Ciona oral siphon (mouth) as a model.
The first aim will use a novel chimera assay in which stem cell niches are swapped between young and old
animals and isolated stem cells are injected into old animals to determine the relative roles of the stem cell
niche, the stem cells themselves, the regeneration blastema, and the surrounding tissue environment in
regenerative aging. This aim will exploit our previous identification of the branchial sac (pharynx) stem cell
niche as the source of progenitor cells that migrate the site of siphon amputation and differentiate into multiple
tissues during regeneration. The second aim is to identify, characterize, and localize the expression of key
regulatory genes that are responsible for robust siphon regeneration in young animals and loss of this capacity
in old animals. This aim will use both a set of pre-existing candidate genes expressed at high levels in the
regenerating siphon of young animals as well as a new set of downregulated and upregulated regulatory genes
expressed in the stem cell niche to be identified by transcriptome sequencing at different stages of the adult life
cycle. The third aim is to determine the functions, hierarchical relationships, and ability to restore lost
regenerative capacity of key regeneration genes by RNAi mediated gene knockdown and amelioration assays
using the chimera approach in old animals. This research is designed to reveal the genetic mechanisms
underlying the loss of regenerative capacity during aging in an invertebrate chordate model with the potential to
clarify our understanding of the evolutionary history and causes of regenerative aging in vertebrates.

## Key facts

- **NIH application ID:** 9816611
- **Project number:** 5R01AG055411-03
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** WILLIAM R JEFFERY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,400
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9816611

## Citation

> US National Institutes of Health, RePORTER application 9816611, The Tunicate Ciona: A New Model for the Effects of Aging on Tissue Regeneration (5R01AG055411-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9816611. Licensed CC0.

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