Aging is associated with alterations in skeletal muscle energy metabolism, insulin resistance and a higher prevalence of type 2 diabetes mellitus (T2DM). Aging is also associated with a progressive loss of muscle mass and increased adiposity, known as sarcopenic obesity, which leads to mobility limitations and disability. However, the causes of insulin resistance and sarcopenia in humans are not known. This project will provide novel information regarding potential factors underlying both metabolic dysfunction and sarcopenia in aging muscle - namely, mitochondria and the accumulation of intramyocellular lipids. Within this conceptual framework we will help elucidate the biological underpinnings of these two significant health problems related to aging. In addition, we will provide intervention-based evidence to better understand these complex age-related disorders and whether mitochondria or intramyocellular lipids are modifiable targets for improved prevention or treatment strategies for metabolic and muscle dysfunction. Therefore, our overall objectives are to employ highly innovative methods in muscle biopsy specimens in order to determine the functional and clinically relevant consequences of these interventions as well as alterations in several novel biochemical and molecular factors potentially underlying these intervention effects on human skeletal muscle.

Public Health Relevance

Dieting to lose weight may have positive benefits in older, overweight men and women. However, these benefits may come at a cost regarding the loss of muscle tissue. This project will provide unique biochemical and molecular targets in human skeletal muscle underlying the benefits as well as the potential negative consequences of dieting to lose weight in older men and women.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG021961-06
Application #
8336930
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Joseph, Lyndon
Project Start
2003-05-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
6
Fiscal Year
2012
Total Cost
$556,978
Indirect Cost
$167,141
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213