Yuanpei College, Peking University, Beijing 100871, China.
Center for Bioinformatics, School of Life Sciences, Peking University, Beijing 100871, China.
Genome Res. 2023 Aug;33(8):1381-1394. doi: 10.1101/gr.277491.122. Epub 2023 Jul 31.
Accurately measuring biological age is crucial for improving healthcare for the elderly population. However, the complexity of aging biology poses challenges in how to robustly estimate aging and interpret the biological significance of the traits used for estimation. Here we present SCALE, a statistical pipeline that quantifies biological aging in different tissues using explainable features learned from literature and single-cell transcriptomic data. Applying SCALE to the "Mouse Aging Cell Atlas" () data, we identified tissue-level transcriptomic aging programs for more than 20 murine tissues and created a multitissue resource of mouse quantitative aging-associated genes. We observe that SCALE correlates well with other age indicators, such as the accumulation of somatic mutations, and can distinguish subtle differences in aging even in cells of the same chronological age. We further compared SCALE with other transcriptomic and methylation "clocks" in data from aging muscle stem cells, Alzheimer's disease, and heterochronic parabiosis. Our results confirm that SCALE is more generalizable and reliable in assessing biological aging in aging-related diseases and rejuvenating interventions. Overall, SCALE represents a valuable advancement in our ability to measure aging accurately, robustly, and interpretably in single cells.
准确测量生物年龄对于改善老年人口的医疗保健至关重要。然而，衰老生物学的复杂性给如何稳健地估计衰老以及解释用于估计的特征的生物学意义带来了挑战。在这里，我们提出了 SCALE，这是一个统计管道，使用从文献和单细胞转录组数据中学习到的可解释特征来量化不同组织中的生物衰老。将 SCALE 应用于“小鼠衰老细胞图谱”（）数据，我们确定了 20 多种鼠组织的组织水平转录组衰老程序，并创建了一个多组织的小鼠定量衰老相关基因资源。我们观察到 SCALE 与其他年龄指标（如体细胞突变的积累）很好地相关，并且即使在相同的生物钟年龄的细胞中也能区分细微的衰老差异。我们还在衰老肌肉干细胞、阿尔茨海默病和异时异体共生的来自衰老相关疾病和恢复干预的数据中，将 SCALE 与其他转录组和甲基化“时钟”进行了比较。我们的结果证实，SCALE 在评估与衰老相关的疾病和恢复干预中的生物衰老方面更具通用性和可靠性。总的来说，SCALE 代表了在单细胞中更准确、稳健和可解释地测量衰老的一个有价值的进展。
