Biological age, an indicator of an individual's health status, was initially measured using bulk tissue aging clocks. However, by averaging molecular signals across thousands of cells, these tools mask the cellular heterogeneity that characterizes aging. Recent single-cell aging clocks, enabled by high-resolution omics technologies, address this limitation. In this review, we provide a systematic overview of these tools, covering their computational foundations and the key biological insights they enable. These clocks have transformed "mosaic aging" from a hypothesis into a quantifiable phenomenon. They also highlight the plasticity of aging by tracking cell-type-specific age acceleration in disease and its reversal after interventions. Furthermore, they are opening new biological frontiers, including the "age reset" during embryogenesis, the role of the tissue microenvironment, and the molecular underpinnings of extreme longevity. Collectively, these findings recast aging not as passive decline but as a regulated, potentially malleable biological program. Single-cell aging clocks provide the foundational tools for developing the next generation of precision interventions aimed at extending human healthspan.
Longevity & Aging