# The AMPK/ULK1/p27Kip1 axis regulates autophagy and cell survival in aged satellite cells

> **NIH NIH K01** · DUKE UNIVERSITY · 2020 · $122,526

## Abstract

a. Project summary/abstract:
Sarcopenia is the age-related loss in skeletal muscle mass and strength; it leads to a host of co-morbidities
including loss of physical function and overall resilience. One such perturbation in persons with sarcopenia is
the diminished ability to regenerate muscle after injury. Muscle stem cells, referred to as satellite cells, are
required to activate, proliferate and differentiate to regenerate muscle and restore physical function. Aged
satellite cells are slower to activate upon injury; susceptible to apoptosis; and less efficient in repairing injured
muscle. The AMPK/ULK1/p27Kip1 pathway appears critical for successful transition from quiescence to entry
into the cell cycle. Our preliminary data identify perturbations in the AMPK/ULK1/p27Kip1 pathway with
advanced age. This award period will investigate the role of the AMPK/ULK1/p27Kip1 pathway in the
phenotype of satellite cell aging in both human and mouse models. In Aim1, we will test the hypothesis that
activation of AMPK and its downstream targets ULK1 and p27Kip1 regulate the autophagy/apoptosis decision
in aged satellite cells. We will use molecular assays to rescue the functional loss of this pathway in aged cells
and return proliferative capacity. In Aim 2, we will test the hypothesis that exercise, a physiological inducer of
AMPK and autophagy, stimulates the AMPK/ULK1/p27Kip1 pathway, thereby enhancing proliferation and
metabolic function in aging murine and human satellite cells. Aim 3 will test the hypothesis that
AMPK/ULK1/p27Kip1 signaling will regulate the beneficial effects of caloric restriction on aged satellite cells.
Together, the experiments in this proposal will test the hypothesis that the AMPK/ULK1/p27Kip1 pathway is
impaired in aging satellite cells resulting in a reduction in autophagy and susceptibility to apoptosis. Key
aspects of Dr. White's career enhancement will be: to learn how to coordinate clinical exercise trials; to train
in methods of satellite cell isolation and metabolic analysis, especially in the context of the aging organism.
The training program will entail dedicated internal and external scientific presentations; pertinent course
work/workshops in stem cell biology and aging; and intensive career mentorship to ensure progress toward
independence. The research and career development plan detailed in this proposal will be conducted with a
team of outstanding mentors. Dr. William E. Kraus, a professor at the Duke Medical School is an established
expert in clinical exercise studies and muscle/satellite cell biology; he will serve as the primary mentor. Drs.
Kenneth Schmader, Deborah Muoio (Duke) and Amy Wagers (Harvard) will serve as co-mentors; they will
facilitate training in aging biology, cell metabolism and aging stem cell biology, respectively. The environment
at the Duke School of Medicine is ideal for the research and training activities outlined in this proposal. This
award will provide Dr. White with optimal tra...

## Key facts

- **NIH application ID:** 9939360
- **Project number:** 5K01AG056664-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** James P. White
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,526
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939360

## Citation

> US National Institutes of Health, RePORTER application 9939360, The AMPK/ULK1/p27Kip1 axis regulates autophagy and cell survival in aged satellite cells (5K01AG056664-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939360. Licensed CC0.

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