RT Journal A1 Mao, Shulin A1 Su, Jiayu A1 Wang, Longteng A1 Bo, Xiaochen A1 Li, Cheng A1 Chen, Hebing T1 A transcriptome-based single-cell biological age model and resource for tissue-specific aging measures JF Genome Research JO Genome Research YR 2023 FD August 01 VO 33 IS 8 SP 1381 OP 1394 DO 10.1101/gr.277491.122 UL http://genome.cshlp.org/content/33/8/1381.abstract AB 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” (Tabula Muris Senis) 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.