Over 100 million individuals in the United States are obese, including the very young and the very old, a condition associated with insulin insensitivity, metabolic inflexibility, and reduced activities of daily living.
Principal Investigator: David L. Williamson, PhD
Funding Agency: University at Buffalo
Abstract: Over 100 million individuals in the United States are obese, including the very young and the very old, a condition associated with insulin insensitivity, metabolic inflexibility, and reduced activities of daily living. Like aged individuals, skeletal muscle proliferative capacity, mass, and function of the obese are decreased. This has a negative metabolic impact, because skeletal muscle is a major site for insulin action and glucose disposal and comprises a large portion of fat free mass, which is positively associated with metabolic homeostasis. There is mounting evidence of increased expression of senescence proteins in obese tissues, similar to that of aged, suggesting premature senescing of obese tissue. Stress-induced premature senescence results in irreversible cell cycle inhibition and reduced growth of tissue that is not aged. Premature cell senescence of skeletal muscle is detrimental to adaptation and growth. Reduced muscle mass can also result from a reduction in mRNA translation and subsequent protein synthesis. Our contention is that normalizing the metabolic variables (e.g. insulin, glucose, lipid) and dysregulated growth pathways, often disturbed in the obese and aging, are equally important for muscle growth. This will be achieved through treatment of obese and/or aged rodents with common anti-diabetes and/or anti-cancer drugs, as well as treadmill exercise.