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Variation in senescent-dependent lung changes in inbred mouse strains.

Kewu Huang1, Wayne Mitzner, Richard Rabold

  • 1Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, Maryland 21205, USA.

Journal of Applied Physiology (Bethesda, Md. : 1985)
|January 16, 2007
PubMed
Summary

Aging accelerates lung structure and function changes in DBA/2J mice more than in C57BL/6J mice, driven by distinct gene expression patterns. These findings highlight strain-specific senescence in mouse lungs.

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Area of Science:

  • Pulmonary physiology
  • Aging research
  • Comparative genomics

Background:

  • Inbred mouse strains exhibit varying lung development.
  • Senescence-dependent differences in lung structure and function are not fully understood across strains.

Purpose of the Study:

  • To investigate age-related changes in lung structure and function between C57BL/6J (B6) and DBA/2J (D2) mice.
  • To identify gene expression differences contributing to strain-specific senescence in mouse lungs.

Main Methods:

  • Quasi-static pressure-volume curves and respiratory impedance measurements in 2- and 20-month-old B6 and D2 mice.
  • Morphometric analysis of lung parenchyma for elastic fiber and collagen content.
  • Quantitative RT-PCR to assess gene expression of elastin, collagen, matrix metalloproteinases, and their inhibitors.

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Main Results:

  • Both strains showed age-dependent increases in lung volume, with a greater proportional increase in D2 mice.
  • D2 mice exhibited decreased elastic recoil and reduced airway resistance with age, unlike B6 mice.
  • Age-related decreases in elastic fibers were observed in both strains, but collagen increased significantly with age in D2 mice.
  • D2 mice showed downregulation of elastin and procollagen genes and upregulation of matrix metalloproteinase 9 (Mmp9).
  • B6 mice showed increased expression of tissue inhibitors of matrix metalloproteinases (Timp1 and Timp4).

Conclusions:

  • Lung mechanics change significantly with age in both B6 and D2 mice.
  • Age-related lung changes are accelerated in D2 mice compared to B6 mice.
  • Strain-specific differences in lung mechanics are associated with distinct age-dependent gene expression profiles.