Research Paper Volume 16, Issue 17 pp 12168—12190
The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies
- 1 Computational Biology Group, CIC bioGUNE-BRTA (Basque Research and Technology Alliance), Bizkaia Technology Park, Derio, Spain
- 2 Computational Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette L-4362, Luxembourg
- 3 Biomedical Data Science Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette L-4362, Luxembourg
- 4 Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia 48012, Spain
Received: March 15, 2024 Accepted: July 19, 2024 Published: September 9, 2024
https://doi.org/10.18632/aging.206105How to Cite
Copyright: © 2024 Hodar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Current rejuvenation strategies, which range from calorie restriction to in vivo partial reprogramming, only improve a few specific cellular processes. In addition, the molecular mechanisms underlying these approaches are largely unknown, which hinders the design of more holistic cellular rejuvenation strategies. To address this issue, we developed SINGULAR (Single-cell RNA-seq Investigation of Rejuvenation Agents and Longevity), a cell rejuvenation atlas that provides a unified system biology analysis of diverse rejuvenation strategies across multiple organs at single-cell resolution. In particular, we leverage network biology approaches to characterize and compare the effects of each strategy at the level of intracellular signaling, cell-cell communication, and transcriptional regulation. As a result, we identified master regulators orchestrating the rejuvenation response and propose that targeting a combination of them leads to a more holistic improvement of age-dysregulated cellular processes. Thus, the interactive database accompanying SINGULAR is expected to facilitate the future design of synthetic rejuvenation interventions.