Calico Life Sciences, South San Francisco, California 94080, USA.
Genome Res. 2019 Dec;29(12):2088-2103. doi: 10.1101/gr.253880.119. Epub 2019 Nov 21.
Aging is a pleiotropic process affecting many aspects of mammalian physiology. Mammals are composed of distinct cell type identities and tissue environments, but the influence of these cell identities and environments on the trajectory of aging in individual cells remains unclear. Here, we performed single-cell RNA-seq on >50,000 individual cells across three tissues in young and old mice to allow for direct comparison of aging phenotypes across cell types. We found transcriptional features of aging common across many cell types, as well as features of aging unique to each type. Leveraging matrix factorization and optimal transport methods, we found that both cell identities and tissue environments exert influence on the trajectory and magnitude of aging, with cell identity influence predominating. These results suggest that aging manifests with unique directionality and magnitude across the diverse cell identities in mammals.
衰老是一个多效过程，影响着哺乳动物生理学的许多方面。哺乳动物由不同的细胞类型和组织环境组成，但这些细胞身份和环境对个体细胞衰老轨迹的影响尚不清楚。在这里，我们对年轻和老年小鼠的三个组织中的超过 50,000 个单个细胞进行了单细胞 RNA-seq，以便能够直接比较细胞类型之间的衰老表型。我们发现，许多细胞类型中都存在衰老的转录特征，而每种类型都有其独特的衰老特征。利用矩阵分解和最优传输方法，我们发现细胞身份和组织环境都对衰老的轨迹和幅度产生影响，其中细胞身份的影响占主导地位。这些结果表明，衰老在哺乳动物的不同细胞身份中表现出独特的方向性和幅度。
