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Insolubilome profiling defines molecular features that influence protein insolubility with aging - PubMed

9 hours ago
  • #aging
  • #protein solubility
  • #proteostasis
  • Insolubilome profiling identifies molecular features affecting protein insolubility during aging.
  • Mass spectrometry reveals tissue-specific insoluble/soluble protein ratios in young mice, varying widely (100-1,000×).
  • Aging alters protein solubility: some proteins become more insoluble, others less, and some remain unaffected.
  • Age-related solubility changes are not solely based on tissue similarity and differ in tissues with varying degeneration tendencies.
  • Structural features correlate with tissue-specific changes in protein solubility with aging.
  • Proteins becoming insoluble in multiple organs include aggregation-prone circulating factors and ectopically expressed proteins.
  • Example: Hornerin, primarily expressed in epidermis, increases in insolubility in aging skeletal muscle; its upregulation causes muscle weakness.
  • Age-insoluble proteins serve as biomarkers and may contribute to functional decline, indicating a complex remodeling of the insolubilome with aging.