Age-Dependent Chromatin Remodeling Drives Inflammatory Dysregulation in Tendon Cells

Area of Science:

• Gerontology
• Molecular Biology
• Musculoskeletal Biology

Background:

• Aging impairs tissue function and cellular stress tolerance.
• Musculoskeletal disorders, like tendon degeneration, are rising with increased lifespan.
• Effective interventions for age-related decline are limited.

Purpose of the Study:

• Investigate how inflammation differentially affects tendon cells from young and aged donors.
• Identify age-dependent regulatory mechanisms governing inflammatory responsiveness.
• Understand the link between epigenetic changes and tendon degeneration.

Main Methods:

• Super-resolution microscopy for chromatin organization.
• Epigenomic and transcriptomic profiling.
• Analysis of TNFα receptor organization and AP-1 transcription factor activity.

Main Results:

• Mature tendon cells show exaggerated inflammatory and catabolic responses.
• Enhanced TNFα receptor organization and pro-inflammatory element accessibility in aged cells.
• AP-1 transcription factors act as central age-dependent regulators, promoting inflammatory programs.

Conclusions:

• Age-dependent epigenetic priming amplifies inflammatory sensitivity in mature tendon cells.
• Reparative gene regulation is constrained in aged tendon cells.
• Findings provide a framework linking chromatin remodeling to tendon degeneration, suggesting epigenetic targets for rejuvenation.