Stiffening symphony of aging: Biophysical changes in senescent osteocytes

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Main Authors: Maryam Tilton, Megan Weivoda, Maria Astudillo Potes, Anne Gingery, Alan Y. Liu, Tamara Tchkonia, Lichun Lu, James L. Kirkland
Format: Artículo Open Access
Published: Wiley 2024
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author Maryam Tilton
Megan Weivoda
Maria Astudillo Potes
Anne Gingery
Alan Y. Liu
Tamara Tchkonia
Lichun Lu
James L. Kirkland
author_facet Maryam Tilton
Megan Weivoda
Maria Astudillo Potes
Anne Gingery
Alan Y. Liu
Tamara Tchkonia
Lichun Lu
James L. Kirkland
Maryam Tilton
Megan Weivoda
Maria Astudillo Potes
Anne Gingery
Alan Y. Liu
Tamara Tchkonia
Lichun Lu
James L. Kirkland
collection Wiley Open Access
contents Stiffening symphony of aging: Biophysical changes in senescent osteocytes Maryam Tilton Megan Weivoda Maria Astudillo Potes Anne Gingery Alan Y. Liu Tamara Tchkonia Lichun Lu James L. Kirkland Aging Cell AbstractSenescent 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 subcellular mechanical measurements with gene expression analyses, we identified significant, time‐dependent alterations in the mechanical properties of senescent bone cells. Increases in classical markers such as SA‐β‐Gal activity and p16Ink4a expression levels confirmed the senescence status post‐irradiation. Our key findings include a time‐dependent increase in cytoskeletal Young's 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 biophysical 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 may support biomechanical stimulation as a potential therapeutic strategy to rejuvenate aging osteocytes and enhance bone health. 10.1111/acel.14421 http://creativecommons.org/licenses/by/4.0/
doi_str_mv 10.1111/acel.14421
format Artículo Open Access
id wiley_oa_10_1111_acel_14421
institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by/4.0/
publishDate 2024
publisher Wiley
record_format wiley_oa
spellingShingle Stiffening symphony of aging: Biophysical changes in senescent osteocytes
Maryam Tilton
Megan Weivoda
Maria Astudillo Potes
Anne Gingery
Alan Y. Liu
Tamara Tchkonia
Lichun Lu
James L. Kirkland
Aging Cell
Stiffening symphony of aging: Biophysical changes in senescent osteocytes Maryam Tilton Megan Weivoda Maria Astudillo Potes Anne Gingery Alan Y. Liu Tamara Tchkonia Lichun Lu James L. Kirkland Aging Cell AbstractSenescent 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 subcellular mechanical measurements with gene expression analyses, we identified significant, time‐dependent alterations in the mechanical properties of senescent bone cells. Increases in classical markers such as SA‐β‐Gal activity and p16Ink4a expression levels confirmed the senescence status post‐irradiation. Our key findings include a time‐dependent increase in cytoskeletal Young's 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 biophysical 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 may support biomechanical stimulation as a potential therapeutic strategy to rejuvenate aging osteocytes and enhance bone health. 10.1111/acel.14421 http://creativecommons.org/licenses/by/4.0/
title Stiffening symphony of aging: Biophysical changes in senescent osteocytes
topic Aging Cell
url https://onlinelibrary.wiley.com/doi/10.1111/acel.14421