Cellular viscous properties in senescence: An emerging biophysical perspective and potential biomarker

Cellular mechanical properties are key regulators of diverse cellular functions. In particular, cellular senescence, a state of permanent cell cycle arrest, is closely associated with mechanical alterations. While extensive efforts have characterized changes in cells' elastic properties such as stiffness and elasticity during senescence, the viscous component of cellular mechanics, governing molecular transport, organelle mobility, and intracellular force dissipation, remains largely unexplored. Emerging evidence suggests that changes in cells' viscous properties, despite receiving limited attention to date, may provide critical insights into cellular state, particularly in the context of senescence and aging. In this review, we define key viscous properties relevant to cellular mechanics and function, summarize experimental approaches for measuring and quantifying these properties, and review existing studies examining viscous properties in aging and senescent cells. We further discuss potential mechanistic origins of alterations in viscous properties during senescence, including cytoskeletal remodeling, macromolecular crowding, and intracellular phase separation. Finally, we evaluate the potential of cellular viscous properties as biomarkers of senescence, promising advances in applications including senescence detection, assessment of aging progression, and administration of senolytic therapies, while also addressing key limitations.