# Mesenchymal Stem Cells as Determinants of Tissue Aging

> **NIH NIH R00** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $248,998

## Abstract

Project Summary/Abstract
 The appearance of fatty and fibrotic infiltration in aged skeletal muscle causes a decline in muscle function
and an increase in metabolic disorders. However, a means to mitigate this detrimental process remains
absent, as the cellular and molecular mechanisms that lead to the intramuscular accumulation of these
adverse atypical tissues are not well understood. Recently identified mesenchymal stem cells (MSCs) that
occupy the interstitial space of skeletal muscle (interstitial MSCs, iMSCs) have been postulated as the
foremost cellular mediators of adiposis and fibrosis. In young tissue iMSCs do not covert to these fates, but
instead, remain as progenitors and are assumed to support the processes of tissue homeostasis and
regeneration. We hypothesize that the fate of iMSCs determine their impact on skeletal muscle and with age,
iMSCs become the adipocytes and fibrocytes that negatively impact the organism as a whole. In the studies of
this proposal, we will define the role of iMSCs in intramuscular fatty and fibrotic infiltration by genetically
targeting the cell in vivo and examining its developmental potential in models of aged skeletal muscle (Aim 1).
We will also determine the necessity of iMSCs in skeletal muscle homeostasis and regeneration in young and
aged milieus by specifically depleting iMSCs in vivo and then examining these activities (Aim 2). Finally, we will
define the molecular pathways of iMSC fate progression by modeling this process in vitro and using advanced
RNA sequencing technologies to reveal non-coding and coding RNA species that can functionally modulate
cell fate determination (Aim 3). Our overarching goal is to elucidate the impact iMSC fate has on skeletal
muscle and to leverage these findings to develop therapeutic targets to mitigate age-related skeletal muscle
decline.
 The candidate, Dr. Michael Wosczyna, has extensive expertise in experimental progenitor cell biology and
has spent more than a decade studying stem cell-related disorders. During the mentoring phase of this award,
Dr. Wosczyna aims to advance his knowledge in age-related stem cell decline and in massively parallel
technologies used for uncovering genetic pathways of fate determination. Dr. Wosczyna's mentor and co-
mentor, Dr. Thomas Rando and Dr. Judith Campisi, respectively, have comprehensive expertise in these
areas. They will provide an enriching environment for Dr. Wosczyna to develop as a prominent independent
investigator in aging research.

## Key facts

- **NIH application ID:** 10130176
- **Project number:** 4R00AG053438-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** MICHAEL WOSCZYNA
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,998
- **Award type:** 4N
- **Project period:** 2016-09-30 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130176

## Citation

> US National Institutes of Health, RePORTER application 10130176, Mesenchymal Stem Cells as Determinants of Tissue Aging (4R00AG053438-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10130176. Licensed CC0.

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