# Engineered Heterochronic Parabiosis on 3D Microphysiological Systems

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $287,147

## Abstract

PROJECT SUMMARY
Heterochronic parabiosis, in which young and aged animals are surgically attached to share circulation, provided
evidence of putative ‘anti-geronic’ factors exist but the mechanisms by which circulating factors mediate
rejuvenating properties on muscle stem cells and their microenvironment have yet to be elucidated. Due to the
complexity of in vivo parabiosis and the dynamic nature of blood-borne factors, reliable identification of these
humoral factors remains a major hurdle. To overcome this challenge, Dr. Jang and his team will leverage
advanced microengineering approaches to build a 3D microfluidic parabiosis circuit that can control mechanical
and biochemical cues in the physiologically relevant 3D microenvironment. In this proposal, his team will further
refine and upgrade the in vitro parabiosis platform by integrating a cell-type-specific protein labeling system
(MetRSL2774G transgene) to precisely identify muscle secretome, also known as myokines, responsible for
rejuvenation effects on muscle stem cells. In addition, the targeted genetics approach will be employed to
delineate oxidative stress-induced pro-geronic myokines that negatively impact muscle stem cell function.
Finally, the team will also engineer an exercise-induced myokine reporter system within parabiosis-on-a-chip
using an optogenetic actuator (Channelrhodopsin 2) co-expressed with protein labeling construct, MetRSL274G.
Using this reporter, proposed studies will identify novel contraction-induced myokines with anti-geronic properties
and myokines that pass the blood-brain-barrier (BBB) to exert their action on muscle-brain crosstalk. The
successful outcomes of this project will have far and broad implications in geroscience. This minimally invasive
3D microphysiological system can be exploited in a variety of studies testing the hallmarks of aging or modeling
of age-related diseases in vitro. More importantly, upon validation, the experimental approach used in this
proposal can be translated to mimic human parabiosis, which will have significant clinical implications.

## Key facts

- **NIH application ID:** 10663683
- **Project number:** 7R01AG072309-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Young Charles Jang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $287,147
- **Award type:** 7
- **Project period:** 2021-04-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10663683

## Citation

> US National Institutes of Health, RePORTER application 10663683, Engineered Heterochronic Parabiosis on 3D Microphysiological Systems (7R01AG072309-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10663683. Licensed CC0.

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