Aging changes cell mechanics and dynamics associated with cytoplasmic crowding.

Aging induces physical changes in organisms, many of which are at the cellular level, but the mechanisms underlying these changes are poorly understood. While the cytoplasm provides a crucial physical environment to host essential cellular processes, how its properties change in aging remains largely unknown. Here, using cells from well-established aging mice models, we first investigate the morphological and dynamic changes of aging cells and how they relate to the physical state of the cytoplasm. We find that aged cells spread larger and rounder and migrate slower than young cells. Using particle fluctuation, optical tweezers, and force spectrum microscopy, we demonstrate that aging increases cytoplasmic stiffness and reduces intracellular movement, even while active intracellular forces increase. In addition, using tomographic phase microscopy, we observe a higher refractive index in aged cells which indicates a denser cytoplasm, hinting that aging causes a more crowded cell interior. This crowding behavior underlines the increased cytoplasmic stiffness and the decreased intracellular movement, thereby influencing the altered cell behavior. Our results imply a crucial physical mechanism behind cellular-level changes due to aging. Though mechanisms behind these observations remain unclear, this understanding of cells' physical nature may support fundamental biological functions explored in aging research.