Age-dependent Dystrophin Loss and Genetic Reconstitution Establish a Molecular Link between Dystrophin and Heart Performance during Aging

Dewayne Townsend, Michael Daly, Jeffrey S. Chamberlain, Joseph M. Metzger

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The aging-related decline in cardiac function is an important public health problem. The molecular basis of age-dependent loss of cardiac function is largely unknown and there are no effective therapies addressing this important form of heart disease. This study evaluates the role of the cytoskeletal protein dystrophin in the process of normal cardiac aging. Here, we show that the cytoskeletal protein dystrophin in the hearts of old mice is significantly decreased to a level of 36% that of young mice, whereas other key members of the dystrophin complex are unchanged. Age-dependent decreased ejection fraction was rescued by systemic delivery of an adeno-associated viral vector harboring a functional micro-dystrophin cassette (48.9 ± 2.5% in untreated aged vs. 61.6 ± 7.4% in treated aged mice, compared to 67.1 ± 2.6% in young mice). These data provide the first direct evidence that decreased dystrophin levels are an important modulator of cardiac function in the aged heart.

Original languageEnglish (US)
Pages (from-to)1821-1825
Number of pages5
JournalMolecular Therapy
Volume19
Issue number10
DOIs
StatePublished - Oct 2011

Bibliographical note

Funding Information:
This work was supported by grants from National Institutes of Health (J.M.M, J.S.C, D.T.), the Lillehei Heart Institute (M.D.) and the Muscular Dystrophy Association (D.T.).

Fingerprint Dive into the research topics of 'Age-dependent Dystrophin Loss and Genetic Reconstitution Establish a Molecular Link between Dystrophin and Heart Performance during Aging'. Together they form a unique fingerprint.

Cite this