Ageing research has focused either on assessing organ- and tissue-based changes, such as lung capacity and cardiac function, or on changes at the molecular scale such as gene expression, epigenetic modifications and metabolism. Here, by using a cohort of 32 samples of primary dermal fibroblasts collected from individuals between 2 and 96 years of age, we show that the degradation of functional cellular biophysical features—including cell mechanics, traction strength, morphology and migratory potential—and associated descriptors of cellular heterogeneity predict cellular age with higher accuracy than conventional biomolecular markers. We also demonstrate the use of high-throughput single-cell technologies, together with a deterministic model based on cellular features, to compute the cellular age of apparently healthy males and females, and to explore these relationships in cells from individuals with Werner syndrome and Hutchinson–Gilford progeria syndrome, two rare genetic conditions that result in phenotypes that show aspects of premature ageing. Our findings suggest that the quantification of cellular age may be used to stratify individuals on the basis of cellular phenotypes and serve as a biological proxy of healthspan.

衰老研究的重点要么是评估基于器官和组织的变化，如肺活量和心脏功能，要么是分子尺度的变化，如基因表达、表观遗传修饰和新陈代谢。在这里，通过使用从 2 到 96 岁的个体中收集的 32 个原代真皮成纤维细胞样本的队列，我们​​表明功能性细胞生物物理特征（包括细胞力学、牵引强度、形态和迁移潜力）和相关描述符的退化细胞异质性的预测比传统的生物分子标记更准确地预测细胞年龄。我们还展示了使用高通量单细胞技术以及基于细胞特征的确定性模型来计算明显健康的男性和女性的细胞年龄，并探索 Werner 综合征和 Hutchinson-Gilford 早衰综合征患者细胞中的这些关系，这两种罕见的遗传病会导致表型显示过早衰老的各个方面。我们的研究结果表明，细胞年龄的量化可用于根据细胞表型对个体进行分层，并作为健康寿命的生物学指标。