# Role of transposon regulation in the negligible senescence of S. mediterranea

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $402,632

## Abstract

PROJECT SUMMARY
The progressive decline in the function of adult stem cells is a major factor in the development of age-related
conditions. Considering the increasing age of the overall human population, identifying strategies to prolong
stem cell health is of major importance. Study of short-lived model systems has identified many potential
limiting factors in the maintenance of stem cells, but has been unable to elucidate whether and how stem cell
aging could be avoided altogether. We will leverage the negligibly senescent system S. mediterranea to reveal
the regulation underlying this animal’s ability to maintain stem cell health seemingly indefinitely. We previously
found that planarian stem cells employ a double layer of protection against transposons, whereas the shorter-
lived differentiated cells retain only a single defense layer, suggesting that transposons could be a significant
threat to stem cell maintenance. Further, loss of transposon silencing leads to rapid lethality in these otherwise
long-lived animals. This project focuses on the role of transposon silencing and chromatin compaction in the
resistance to aging phenotypes of planarian tissues. We intend to leverage our recent finding of stereotypic
age-related markers in planarian differentiated cells to determine the role of various pathways in the
progression of planarian aging. Aim 1 of this proposal seeks to elucidate whether changes in transposon levels
or in chromatin regulation can change the rate of aging in planarian differentiated tissues. Aim 2 addresses the
role of various transposon-related pathways in the indefinite maintenance of planarian stem cells. Aim 3 will
determine whether there is a correlation between the lifespan of a planarian tissue type and its control of
transposons. Furthermore, the genomic locations of age-related changes in chromatin modifications will be
addressed.
This project will provide new insights in the workings of a negligibly senescent system. Understanding of the
mechanisms it employs in the long-term maintenance of its actively dividing stem cell population will provide
new avenues to pursue in search for strategies to extend human stem cell health.

## Key facts

- **NIH application ID:** 10518521
- **Project number:** 1R01AG078926-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Josephina C van Wolfswinkel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,632
- **Award type:** 1
- **Project period:** 2022-07-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518521

## Citation

> US National Institutes of Health, RePORTER application 10518521, Role of transposon regulation in the negligible senescence of S. mediterranea (1R01AG078926-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10518521. Licensed CC0.

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