# Molecular signature of parabiosis

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $472,200

## Abstract

PROJECT SUMMARY
Aging is the single greatest cause of disease and death worldwide, and rejuvenating the body by targeting
biological aging processes therefore holds potential to simultaneously prevent multiple chronic diseases like
cancer, heart disease, dementia, and diabetes. While decades of research has unveiled common hallmarks of
aging, like mitochondrial dysfunction, inflammation, and loss of proteostasis, therapies targeting these hallmarks
have elicited only modest rejuvenation in animal models. This may be in part because most aging studies have
focused on only one or a few organs or cell types, with little to no temporal resolution, limiting our ability to
interpret how and when aging impacts these interconnected systems. Recently, however, we have attempted
such a systematic characterization of aging. Using bulk RNA-sequencing (RNA-seq) and single-cell RNA-
sequencing (scRNA-seq) on dozens of mouse organs and cell types across the lifespan (termed Tabula Muris
Senis), we discovered global and specific aging signatures throughout the body. But it remains unknown how,
or if, rejuvenation paradigms affect these global aging pathways, or rather instigate nascent biochemical
programs. The rational design of new therapeutics is therefore challenging.
 One method of rejuvenation which has garnered beneficial effects across organ systems is heterochronic
parabiosis, in which a young and old mouse share a common circulation. Phenotypes like cognition, muscle
strength, and bone repair have all shown functional improvement through exposure to young blood. Parabiosis
research has largely focused on age-related changes to circulating proteins, and several have been determined
to mediate at least some of the observed effects. However, such individual factors have yet to achieve robust
rejuvenation throughout the body, likely in part due to an incomplete understanding of the effects of parabiosis
on disparate organs and cells. Using our newly created Tabula Muris Senis data to represent normal aging, we
investigated scRNA-seq changes in 3 tissues following parabiosis: gonadal and mesenteric adipose tissues,
which undergo age-related gene expression changes prior to other organs, and liver, as hepatocytes were one
of the first cell types observed to benefit from exposure to a young circulatory system. Interestingly, individual
cell types vary greatly in their response to parabiosis, with vascular endothelial cells from all 3 tissues showing
prominent transcriptomic changes consistent with normal aging genes.
 It is our hope that by expanding this analysis to scRNA-seq of 9 tissues, and to bulk RNA-seq of 21
tissues, we can discover signatures that will serve as the basis for identifying small molecules capable of robust
rejuvenation and healthspan extension. As surgically intensive parabiosis is confounded by cell trafficking and
simultaneous exposure to young and aged circulating factors, we further propose to compare parabiosis
signatures to those ...

## Key facts

- **NIH application ID:** 10820571
- **Project number:** 5R01AG072255-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** TONY WYSS-CORAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $472,200
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820571

## Citation

> US National Institutes of Health, RePORTER application 10820571, Molecular signature of parabiosis (5R01AG072255-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10820571. Licensed CC0.

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