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Aging involves complex, interconnected processes across multiple organs. This study reveals coordinated gene expression shifts and immune cell activation during aging in mice, offering insights into systemic health decline.

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Area of Science:

  • Gerontology
  • Molecular Biology
  • Immunology

Background:

  • Aging is the primary risk factor for global disease and mortality.
  • Understanding aging mechanisms is crucial for improving healthspan.
  • Previous studies identified key aging damage categories but lacked whole-organism analysis.

Purpose of the Study:

  • To comprehensively analyze aging dynamics across multiple organs in a whole-organism context.
  • To identify and characterize gene expression and protein level changes during aging.
  • To investigate the interplay between tissue-specific and systemic aging processes.

Main Methods:

  • Bulk RNA sequencing of 17 organs and plasma proteomics in mice at 10 different ages.
  • Integration with single-cell RNA sequencing data from the Tabula Muris Senis.
  • Analysis of gene expression trajectories and protein level correlations.

Main Results:

  • Identified linear and nonlinear gene expression shifts during aging, clustered into functional groups like extracellular matrix, protein homeostasis, mitochondrial function, and immune response.
  • Observed similar gene expression patterns across tissues, varying in onset and magnitude.
  • Detected widespread immune cell activation, particularly T and B cells in adipose tissue, starting in middle age.
  • Found strong correlations between tissue gene expression changes and plasma protein levels.

Conclusions:

  • Aging progresses asynchronously within and between organs, yet exhibits coordinated molecular signatures.
  • Immune system activation, especially in adipose tissue, is a key feature of aging.
  • Systemic circulation reflects tissue-specific aging changes, providing potential biomarkers for health decline.