Biology subjects

Tilton, M.

Publications and source records attributed to Tilton, M..

2 recordsLinked to original sources

bioRxiv2024

Tracing Cellular Senescence in Bone: Time-Dependent Changes in Osteocyte Cytoskeleton Mechanics and Morphology

Aging-related bone loss significantly impacts the growing elderly population globally, leading to debilitating conditions such as osteoporosis. Senescent osteocytes play a crucial role in the aging process of bone. This longitudinal study examines the impact of continuous local and paracrine exposure to senescence-associated secretory phenotype (SASP) factors on senescence-associated biophysical and biomolecular markers in osteocytes. We found significant cytoskeletal stiffening in irradiated osteocytes, accompanied by expansion of F-actin areas and a decline in dendritic integrity. These changes, correlating with alterations in pro-inflammatory cytokine levels and osteocyte-specific gene expression, support the reliability of biophysical markers for identifying senescent osteocytes. Notably, local accumulation of SASP factors had a more pronounced impact on osteocyte properties than paracrine effects, suggesting that the interplay between local and paracrine exposure could substantially influence cellular aging. This study underscores the importance of osteocyte mechanical and morphological properties as biophysical markers of senescence, highlighting their time-dependence and differential effects of local and paracrine SASP exposure. Collectively, our investigation into biophysical senescence markers offer unique and reliable functional hallmarks for non-invasive identification of senescent osteocytes, providing insights that could inform therapeutic strategies to mitigate aging-related bone loss.

biophysics↗

bioRxiv2024

Stiffening Symphony of Aging: How Senescent Osteocytes Lose Their Elastic Rhythm

Senescent osteocytes are key contributors to age-related bone loss and fragility; however, the impact of mechanobiological changes in these cells remains poorly understood. This study provides a novel analysis of these changes in primary osteocytes following irradiation-induced senescence. By integrating sub-cellular mechanical measurements with gene expression analyses, we identified significant, time-dependent alterations in the mechanical properties of these cells. Increases in SA-{beta}-Gal activity and p16Ink4a expression levels confirmed the senescence status post-irradiation. Key findings include a time-dependent increase in cytoskeletal Youngs modulus and altered viscoelastic properties of the plasma membrane, affecting the contractility of primary osteocytes. Additionally, we observed a significant increase in Sclerostin (Sost) expression 21 days post-irradiation. These mechanobiological changes may impair osteocyte mechanosensation and mechanotransduction, contributing to bone fragility. This is the first study to time-map senescence-associated mechanical changes in the osteocyte cytoskeleton. Our findings highlight the potential of biophysical markers as indicators of cellular senescence, providing more specificity than traditional, variable biomolecular markers. We believe these results support biomechanical stimulation as a potential therapeutic strategy to rejuvenate aging osteocytes and enhance bone health.

cell biology↗