Age-related changes in lamin A/C expression in cardiomyocytes.
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.
Afilalo
Jonathan
J
Division of Internal Medicine, Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montréal, Québec, Canada.
Sebag
Igal A
IA
Chalifour
Lorraine E
LE
Rivas
Daniel
D
Akter
Rahima
R
Sharma
Kamal
K
Duque
Gustavo
G
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004452:Echocardiography; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology
D034904:Lamin Type A; C440308:lamin C