image: Figure 4. Mechanistic insights from a combined approach of all tools used by SINGULAR. (A) Recapitulation of well documented cell communication pathway for Macrophage recruitment under the Parabiosis condition. Ccr2 recognizes Ccl2, which initiates a signaling cascade to activate the AP-1 complex, which leads to the activation of chemotaxis genes. (B) Further validation of this well-known pathway from gene set Enrichment analysis of the members of the connected component of TRN and signaling cascade crosstalk for Gnai2 as a signalling intermediate and Fos, Jun and Cepbp as TRN TFs. Values have been averaged from several related functions, full results in Supplementary Table 4. (C) Novel signaling cascade. In Purkinje cells of the cerebellum, Fgf10 binds to Fgfr2, initiating a cascade in which Pkrca leads to the activation of Mapk1, which recruits Runx2 for further expression of the Fgfr2 receptor, as well as a separate Creppb-mediated signaling cascade that ends with Tcf12 activating Pax6, a transcription factor known for its neuroprotective properties. (D) Intersection between druggable activating TFs in DrugBank and the master regulators uncovered in this study. (E) Number of druggable key signaling molecules for every integrated TRN and signalling cascade.
Credit: 2024 Hodar et al.
“Thus, we expect SINGULAR to be of great utility in informing further advances in human age reversal.”
BUFFALO, NY- September 16, 2024 – A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 17 on September 9, 2024, entitled, “The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies.”
As highlighted in the study's abstract, current rejuvenation strategies—ranging from calorie restriction to in vivo partial reprogramming—tend to improve only a few specific cellular processes. In addition, the molecular mechanisms behind these approaches remain largely unknown, which limits the development of more comprehensive cellular rejuvenation strategies.
To tackle this challenge, researchers Javier Arcos Hodar, Sascha Jung, Mohamed Soudy, Sybille Barvaux, and Antonio del Sol from CIC bioGUNE-BRTA (Basque Research and Technology Alliance in Derio, Spain), Luxembourg Centre for Systems Biomedicine (LCSB), and the Ikerbasque, Basque Foundation for Science (Bilbao, Bizkaia, Spain), developed SINGULAR (Single-cell RNA-seq Investigation of Rejuvenation Agents and Longevity)—a cell rejuvenation atlas that offers a comprehensive systems 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.”
The researchers also analyzed the effects of six rejuvenation strategies across nine studies, involving 73 cell types, at multiple levels: gene regulatory networks, intracellular signaling, cell-cell communication, and cellular processes. They identified master regulators at each level of biological organization and uncovered common targets across immune cells. Lastly, they demonstrated how SINGULAR can be used to select drugs that mimic the effects of complex interventions.
“Thus, we expect SINGULAR to be of great utility in informing further advances in human age reversal.”
Continue reading: DOI: https://doi.org/10.18632/aging.206105
Correspondence Author: Antonio del Sol – antonio.delsol@uni.lu
Video short: https://www.youtube.com/watch?v=xjpZgdq4BTc
Keywords: rejuvenation, computational biology, scRNA-seq, aging, database, cellular biology
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Journal
Aging-US
Method of Research
News article
Subject of Research
Cells
Article Title
The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies
Article Publication Date
9-Sep-2024
COI Statement
The authors declare no conflicts of interest related to this study.