Date of Award

4-8-2010

Document Type

Thesis

First Advisor

Gary Krishnan: Advisor

Second Advisor

Kevin Moore: Convener

Third Advisor

Kevin Kinney: Third Reader

Abstract

Muscle atrophy and weakening are major health care concerns. For instance sarcopenia, which is a condition of extreme muscle loss and weakening due to aging, was estimated to have cost over 18.5 billion for the year 2000 in the US (Dirks & Leeuwenburgh, 2005). Abilities that depend upon muscle quality like strength, functional mobility, and balance are all key components for how people evaluate their self-rated health (SRH) and quality of life (QoL) (Ozcan et al., 2005; Sirola et al., 2010). Interestingly, SRH and QoL also serve as strong predictors for institutionalization, disability, and mortality for elderly populations (Marzetti & Leeuwenburgh, 2006; Ozcan et al., 2005; Sirola et al., 2010). Two negative growth regulators myostatin (Gdf8) and activin A were investigated in hopes of better understanding the molecular and microscopic behaviors behind muscle atrophy and regeneration. A muscle specific promoter linked to the target gene was used to over-express these constructs in the gastrocnemius (calf) muscle of sexually mature female mice. Myostatin could not be over-expressed, but activin A was successfully over-expressed in vivo through electrotransduction gene transference. In only three weeks, the over-expression of activin A revealed 1-2 fold greater muscle atrophy when compared to the control vector transduced animals. These results indicate for the first time that local overexpression of Activin A in muscle tissue results in significant muscle atrophy.

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