Computational Biology Group, CIC bioGUNE-BRTA (Basque Research and Technology Alliance), Bizkaia Technology Park, Derio, Spain.
Computational Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette L-4362, Luxembourg.
Aging (Albany NY). 2024 Sep 9;16(17):12168-12190. doi: 10.18632/aging.206105.
Current rejuvenation strategies, which range from calorie restriction to 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.
当前的衰老逆转策略，从热量限制到部分重编程，仅能改善少数特定的细胞过程。此外，这些方法的分子机制在很大程度上尚不清楚，这阻碍了更全面的细胞衰老逆转策略的设计。为了解决这个问题，我们开发了 SINGULAR（单细胞 RNA-seq 研究衰老逆转剂和寿命），这是一个细胞衰老逆转图谱，提供了在单细胞分辨率下对多种器官的不同衰老逆转策略的统一系统生物学分析。特别是，我们利用网络生物学方法来描述和比较每种策略在细胞内信号、细胞间通讯和转录调控水平上的作用。结果，我们确定了协调衰老逆转反应的主要调控因子，并提出靶向它们的组合可以更全面地改善与年龄相关的失调的细胞过程。因此，伴随 SINGULAR 的交互式数据库有望促进未来合成衰老逆转干预措施的设计。
