# Novel longevity enhancing pathways regulated by mTOR

> **NIH NIH R01** · DREXEL UNIVERSITY · 2022 · $396,259

## Abstract

ABSTRACT/SUMMARY
Inhibitors of the mTOR pathway are among the most promising interventions to target age-related
dysfunction, however, there is a critical need to further define the pro longevity effects to facilitate clinical
development of mTOR inhibitors. The current proposal will significantly advance this effort providing new
targets for intervention and novel markers to monitor individual responses to mTOR inhibition. The
overarching goal of this research program is to develop a mechanistic understanding of novel downstream
targets of rapamycin, in order to facilitate safer and more effective strategies to promote healthy aging.
Cellular senescence occurs in both somatic and stem cell populations and contributes to age-related
dysfunction, and our laboratory has shown that mTOR inhibition using rapamycin, can prevent entry into the
senescent state. The mTOR pathway also regulates senescence a n d pluripotency in a variety of stem cell
populations. The central hypothesis of the application is that mTOR inhibition by rapamycin prevents
senescence and enhances pluripotency by increasing the lncRNA H19. The rationale for this hypothesis is
our observation that rapamycin increases levels of the non- coding RNA (lncRNA) H19. We find that levels of
H19 decrease during senescence and in pluripotent cells. H19 plays a central role during development and
differentiation, and maintenance of adult stem cell populations. Rapamycin increases H19 levels, prevents
senescence and maintains pluripotency. The results suggest that increasing H19 levels in response to mTOR
inhibition may play a dual role, inhibiting senescence while simultaneously increasing pluripotency in adult
stem cell populations. The proposed work will provide transformative data regarding a novel mechanism for
lifespan extension and improvement of late-life function in multiple tissues.

## Key facts

- **NIH application ID:** 10446243
- **Project number:** 1R01AG071815-01A1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** CHRISTIAN SELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,259
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446243

## Citation

> US National Institutes of Health, RePORTER application 10446243, Novel longevity enhancing pathways regulated by mTOR (1R01AG071815-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10446243. Licensed CC0.

---

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