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1 Montreal, Canada; Medicine, Jewish General Hospital, Montreal, Canada
2 Medicine, Jewish General Hospital, Montreal, Canada
3 Cardiology, Lady Davis Institute for Medical Research, Montreal, Canada
4 Lady Davis Institute for Medical Research, Montreal, Canada
5 Geriatric Medicine, McGill University, Montreal, Canada; Medicine, Jewish General Hospital, Montreal, Canada; Lady Davis Institute for Medical Research, Montreal, Canada
* To whom correspondence should be addressed. E-mail: gustavo.duque{at}mcgill.ca.
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 months) versus young (4 months) 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: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.
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