Age-related changes in lamin A/C expression in cardiomyocytes

Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1451-6. doi: 10.1152/ajpheart.01194.2006. Epub 2007 May 18.

Abstract

Lamin A and C (A/C) are type V intermediate filaments that form the nuclear lamina. Lamin A/C mutations lead to reduced expression of lamin A/C and diverse phenotypes such as familial cardiomyopathies and accelerated aging syndromes. Normal aging is associated with reduced expression of lamin A/C in osteoblasts and dermal fibroblasts but has never been assessed in cardiomyocytes. Our objective was to compare the expression of lamin A/C in cardiomyocytes of old (24 mo) versus young (4 mo) C57Bl/6J mice using a well-validated mouse model of aging. Lamin B1 was used as a control. Immunohistochemical and immunofluorescence analyses showed reduced expression of lamin A/C in cardiomyocyte nuclei of old mice (proportion of nuclei expressing lamin A/C, 9% vs. 62%, P < 0.001). Lamin A/C distribution was scattered peripherally and perinuclear in old mice, whereas it was homogeneous throughout the nuclei in young mice. Western blot analyses confirmed reduced expression of lamin A/C in nuclear extracts of old mice (ratio of lamin A/C to B1, 0.6 vs. 1.2, P < 0.01). Echocardiographic studies showed increased left ventricular wall thickness with preserved cavity size (concentric remodeling), increased left ventricular mass, and a slight reduction in fractional shortening in old mice. This is the first study to show that normal aging is associated with reduced expression and altered distribution of lamin A/C in nuclei of cardiomyocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • Cell Nucleus / metabolism
  • Echocardiography
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Mutation / genetics
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology

Substances

  • Lamin Type A
  • lamin C