• Jensen, Michael Dennis (PI)
  • Klee, George G (PI)
  • Sreekumaran, K. (PI)
  • Sreekumaran, K. (PI)
  • Rizza, Robert Allan (PI)

Project: Research project

Project Details


The progressive decline in muscle mass, strength, and maximal aerobic
capacity and increased fatiguability in the aging population is a major
public health problem of our society. An important question in the
investigation of this aging-related problem is what is the pathogenesis of
this aging-related sarcopenia and whether it is partially or completely
reversible by therapeutic interventions. Previous studies using whole body
measurements failed to elucidate the biochemical basis of age-related
sarcopenia, although, measurements of mixed muscle protein synthesis
indicated that a decline in synthesis rate of muscle protein is a factor
in the pathogenesis of sarcopenia. Recent development of techniques to
measure synthetic rates of specific proteins such as myosin heavy chain
and mitochondrial protein demonstrated that a decline in synthesis rate of
these proteins could cause a decline in muscle strength and V02 max. The
current proposal will determine whether interventions such as testosterone
replacement in the elderly men and DHEA replacement in elderly men and
women will positively affect changes in muscle mass, muscle function and
V02 max in the elderly population. It is hypothesized that while androgens
increase synthetic rates of myosin heavy chain, which is a major
contractile protein resulting in increased muscle mass and muscle strength
only combined aerobic and resistance training increase synthesis rate of
both myosin heavy chain and mitochondrial protein, thereby enhancing not
only muscle strength and mass but also V02 max. Studies will be performed
in 80 elderly men with low testosterone and DHEA and 60 elderly women with
low DHEA. Studies will be performed at baseline t a 3 month interval (to
determine the immediate effects) and then after one year of the
interventions. The results will be compared with 20 young men and women
18-30 years old. It is anticipated that the proposed studies will not only
help in defining the effects of androgen replacement on the quantity and
quality of muscle, but also provide insight into the biochemical basis of
their action and their potential benefits and risks as future hormone
replacements approach in the elderly population. A unique aspect of this
study is the ability to compare these results from studies on muscle with
that of insulin action substrate metabolism and bone turnover.
Effective start/end date7/1/986/30/06


  • Medicine(all)