Departments of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
Department of Chemical and Biomolecular Engineering, Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, MD, 21218, USA.
Commun Biol. 2021 Jan 19;4(1):81. doi: 10.1038/s42003-020-01605-w.
Ageing in humans is associated with the decreased capacity to regulate cell physiology. Cellular properties, such as cell morphology and mechanics, encode ageing information, and can therefore be used as robust biomarkers of ageing. Using a panel of dermal fibroblasts derived from healthy donors spanning a wide age range, we observe an age-associated decrease in cell motility. By taking advantage of the single-cell nature of our motility data, we classified cells based on spatial and activity patterns to define age-dependent motility states. We show that the age-dependent decrease in cell motility is not due to the reduced motility of all cells, but results from the fractional re-distribution among motility states. These findings highlight an important feature of ageing cells characterized by a reduction of cellular heterogeneity in older adults relative to post-adolescent/adults. Furthermore, these results point to a mechanistic framework of ageing, with potential applications in deciphering emergent ageing phenotypes and biomarker development.
人类衰老与调节细胞生理功能的能力下降有关。细胞特性,如细胞形态和力学特性,编码衰老信息,因此可以作为衰老的可靠生物标志物。我们使用一组源自健康供体、年龄跨度较大的真皮成纤维细胞,观察到细胞迁移能力随年龄的相关性下降。利用我们的迁移数据的单细胞性质,我们根据空间和活动模式对细胞进行分类,以定义与年龄相关的迁移状态。我们表明,细胞迁移能力的年龄相关性下降不是由于所有细胞的迁移能力降低,而是由于迁移状态之间的分数再分布所致。这些发现突出了衰老细胞的一个重要特征,即与青少年/成年人相比,老年人的细胞异质性降低。此外,这些结果为衰老机制框架提供了线索,在破译新兴的衰老表型和生物标志物开发方面具有潜在的应用价值。