细胞类型特异性衰老时钟,用于量化大脑神经发生区域的衰老和年轻化。
Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain.
机构信息
Department of Genetics, Stanford University, Stanford, CA, USA.
Genetics Graduate Program, Stanford University, Stanford, CA, USA.
出版信息
Nat Aging. 2023 Jan;3(1):121-137. doi: 10.1038/s43587-022-00335-4. Epub 2022 Dec 19.
The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic regions for two interventions-heterochronic parabiosis and exercise. Aging clocks revealed that heterochronic parabiosis and exercise reverse transcriptomic aging in neurogenic regions, but in different ways. This study represents the first development of high-resolution aging clocks from single-cell transcriptomic data and demonstrates their application to quantify transcriptomic rejuvenation.
细胞类型的多样性是量化衰老及其逆转的一个挑战。在这里,我们开发了基于单细胞转录组学的“衰老时钟”,以描述细胞类型特异性的衰老和恢复活力。我们从 28 只小鼠的侧脑室神经生成区生成了单细胞转录组,覆盖了从年轻到年老的各个年龄段。我们训练了基于单细胞的回归模型,以预测生理年龄(神经干细胞增殖能力)和生物钟年龄。这些衰老时钟可推广到其他小鼠、大脑其他区域和其他物种的独立队列中。为了确定这些衰老时钟是否可以量化转录组的年轻化,我们生成了两个干预措施——异时性联体共生和运动的神经生成区的单细胞转录组数据集。衰老时钟显示,异时性联体共生和运动在神经生成区逆转了转录组的衰老,但方式不同。这项研究代表了首次从单细胞转录组数据开发高分辨率衰老时钟,并展示了它们在量化转录组年轻化方面的应用。