# Heterochronic parabiosis uncovers AdipoR1 as a critical player in retinal rejuvenation

## TL;DR

This study finds that AdipoR1 is crucial for reversing retinal aging, using young blood factors to rejuvenate old retinas.

## Contribution

Identifies AdipoR1 as a novel therapeutic target for retinal aging through heterochronic parabiosis and single-cell RNA sequencing.

## Key findings

- Systemic factors from young mice rejuvenate aged retinas and reduce senescent phenotypes.
- AdipoR1 and AMPK signaling are central to retinal rejuvenation mechanisms.
- AdipoRon treatment reverses retinal aging by enhancing mitochondrial function.

## Abstract

Aging induces substantial structural and functional decline in the retina, yet the molecular drivers of this process remain elusive. In this study, we used heterochronic parabiosis (HP) combined with single-cell RNA sequencing to generate comprehensive transcriptomic profiles of murine retinas from young, aged, and HP pairs, aiming to identify antiaging targets. Our analysis revealed extensive transcriptional alterations across retinal cell types with aging. HP experiments demonstrated that systemic factors from young mice rejuvenated aged retinas and alleviated senescent phenotypes, while aged blood accelerated aging in young mice. Integrative analysis pinpointed adiponectin receptor 1 (AdipoR1) and the downstream adenosine 5′-monophosphate–activated protein kinase (AMPK) signaling pathway as central to the molecular mechanisms underlying retinal rejuvenation. Treatment with the AdipoR1 agonist AdipoRon reversed retinal aging. Mechanistically, AdipoR1-AMPK activation promoted mitochondrial function, contributing to the restoration of youthful cellular phenotypes. Together, our study identifies AdipoR1 as a therapeutic target for retinal aging and provides insights into the molecular programs driving retinal rejuvenation.

AdipoR1 is a key antiaging target uncovered by heterochronic parabiosis, offering insights into retinal aging and rejuvenation.