# Aging-associated dysregulation of the hypoxia pathway limits skeletal muscle regeneration

> **NIH NIH K76** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $241,976

## Abstract

Project Summary/Abstract
 This proposal describes a five-year training program and career development plan for Dr. Indranil
Sinha. Dr. Sinha is a prior trainee of a National Institute of Aging-sponsored Postdoctoral Individual National
Research Service Award (F32). He is a current awardee of a Research and Education Core Grant through the
Boston Pepper Center and the National Institute of Aging. He has completed clinical training in Plastic and
Reconstructive Surgery and is board-certified through the American Board of Plastic Surgery. He is now
embarking on a research and career development program under the mentorship of Amy Wagers, Ph.D.,
Professor of Medicine, Harvard Medical School. Dr. Wagers is an accomplished researcher in skeletal muscle
regeneration and has a history of mentoring trainees who go on to successful, independent research careers.
Additional mentoring will be provided by Dr. Shalender Bhasin, a world-renowned researcher on sarcopenia,
and Dr. Laurie Goodyear, an expert on exercise physiology. Dr. Sinha's career development plan includes
utilization of educational resources at Brigham and Women's Hospital, Joslin Diabetes Center, and Harvard
Medical School. Career development support will also be provided by the Brigham and Women's Hospital
Department of Surgery, where the principle investigator will serve as an attending physician during the period
of funding. Dr. Sinha has developed a clear timeline for publication of his work in peer-reviewed journals,
presentations at national meetings, establishment of an Aging Interest Group within Plastic Surgery, and plans
for the development of independent research projects and continued research funding.
 Dr. Sinha is interested in developing novel treatment strategies for aging-associated loss of skeletal
muscle regeneration. He is investigating mechanisms by which aging alters hypoxia pathway signaling and
skeletal muscle regenerative potential in a murine model. He found that two key factors in the hypoxia
pathway, aryl hydrocarbon receptor nuclear translocator (ARNT) and vascular endothelial growth factor
(VEGF), are severely dysregulated in skeletal muscle in aging and may lead to a loss of skeletal muscle
regenerative potential. Furthermore, using a genetically modified mouse model, he demonstrated that muscle
specific loss of ARNT recapitulates diminished skeletal muscle regeneration as associated with aging. Building
on these intriguing preliminary data, the central goals of this project are to (1) mechanistically define the role of
hypoxia pathway signaling and its impact on muscle regeneration in aging, (2) identify interventions to restore
ARNT and VEGF signaling to preserve skeletal muscle myogenic potential, and (3) determine whether muscle
hypertrophy in response to exercise, which is known to require skeletal muscle regeneration and hypoxia
signaling, is limited in aging secondary to loss of ARNT.

## Key facts

- **NIH application ID:** 10166755
- **Project number:** 5K76AG059996-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Indranil Sinha
- **Activity code:** K76 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,976
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166755

## Citation

> US National Institutes of Health, RePORTER application 10166755, Aging-associated dysregulation of the hypoxia pathway limits skeletal muscle regeneration (5K76AG059996-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10166755. Licensed CC0.

---

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