# Assessing healthspan and epigenetics in aged mice after prolonged exposure to young circulation

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $241,500

## Abstract

Abstract: Aging has profound deleterious effects across all tissues, especially apparent in
skeletal muscle. Age-related loss in skeletal muscle mass and function, referred to as
sarcopenia, is associated with decreased muscle strength and mobility, greater risk of falls, and
an inability to recovery from injury. Currently there are limited therapies to delay the onset of this
condition. Heterochronic blood exchange has rejuvenating effects in the old recipient, showing
enhancing function in various tissues, including skeletal muscle. The parabiosis and blood
plasma transfer models are established methods to deliver youthful circulation to old mice.
However, these models have several limitations that restrict our understanding of how they
affect the aging process. Such limitations include restricted data collection due to physical
attachment of the parabionts, understanding long-term effects of blood sharing and the need for
continuous plasma injections to the aged mouse. To eliminate these limitations, we have
modified the parabiosis/detachment model, allowing various lifespan/healthspan measurements
in aged mice after prolonged exposure to young blood. Therefore, the objective of this R21
application is to characterize the parabiosis/detachment model and determine if prolonged (12
weeks) heterochronic parabiosis at the initial onset of sarcopenia will alter muscle healthspan
and epigenetic patterns after detachment. The rationale for the project is based on preliminary
data suggesting lifespan extension and improved physical function and regenerative capacity in
the detached mice after heterochronic parabiosis. Therefore, we hypothesize prior
heterochronic parabiosis will extend muscle function and result in epigenetic reprogramming in
whole muscle tissue and satellite cells, emulating a youthful state. This research study will
pursue two specific aims: Aim 1 will determine if prolonged exposure to youthful circulation can
delay the development of sarcopenia during anastomose and continue after detachment.
Muscle healthspan will be investigated through measurement of muscle mass,
locomotive/contractile function and regenerative capacity. Aim 2 will determine if prolonged
exposure to youthful circulation can alter epigenetics of whole muscle and satellite cells in aged
mice. Mice will undergo either heterochronic or isochronic parabiosis from 20-23 months of age,
designed to expose the old mouse to youthful circulation at the onset of sarcopenia. Functional
and molecular measurements will be taken during parabiosis and one month after detachment.
This project is highly innovative in the utility of a modified parabiosis/detach model that will allow
investigation of long-term effects on healthspan and epigenetics. The proposed research is
significant because it will address gaps in knowledge that have persisted over the past few
decades due to limitations in current models. The ability to detach heterochronic parabiosis
pairs will allow us to inve...

## Key facts

- **NIH application ID:** 9979231
- **Project number:** 1R21AG065943-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** James P. White
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $241,500
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979231

## Citation

> US National Institutes of Health, RePORTER application 9979231, Assessing healthspan and epigenetics in aged mice after prolonged exposure to young circulation (1R21AG065943-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979231. Licensed CC0.

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