# Novel longevity enhancing pathways regulated by mTOR

> **NIH NIH R56** · DREXEL UNIVERSITY · 2021 · $310,489

## Abstract

Abstract
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 and 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 noncoding 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:** 10358671
- **Project number:** 1R56AG071815-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** CHRISTIAN SELL
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $310,489
- **Award type:** 1
- **Project period:** 2021-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358671

## Citation

> US National Institutes of Health, RePORTER application 10358671, Novel longevity enhancing pathways regulated by mTOR (1R56AG071815-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10358671. Licensed CC0.

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