MECHANISM OF MUSCLE WASTING IN AGING MAN

Project: Research project

Description

Skeletal muscle mass declines with advancing age. This skeletal muscle
loss is a major cause of frailty in the elderly. Important questions in
the study of aging are what the mechanisms of this loss of skeletal
muscle are and whether it is reversible by therapeutic interventions.
Previous studies using indirect measurements of whole-body protein
synthesis have failed to elucidate the biochemical basis of age-related
muscle wasting. The primary goal of this proposal is to determine the
effect of aging on muscle protein synthesis. The secondary goal is to
determine whether this process is reversible by resistance training. We
will test the hypotheses that aging decreases IGF-I production in
skeletal muscle and the effect of IGF-I on muscle protein is reduced in
the elderly. We will measure (13C)leucine abundance in total protein and
myosin of serial skeletal muscle biopsy samples obtained during
continuous infusion of L-(1-13C)leucine. Fractional (total and myosin)
protein synthesis rate will be calculated using (13C)ketoisocaproate as
the precursor pool. A forearm technique using (ring-2H5)phenylalanine as
a tracer will be used to estimate muscle protein breakdown and its
relative contribution to whole body protein dynamics, to study the local
effect of IGF-I on muscle protein synthesis and degradation, and to
assess whether the elderly demonstrate resistance to IGF-I's anabolic
effect. In order to assess the molecular basis for changes in myosin
synthesis rates and distinguish between translational and
pretranslational levels of regulation, we will compare changes in the
fractional synthesis rate of myosin to the relative abundance of
messenger RNA coding for myosin heavy chain in skeletal muscle biopsies.
We will also measure total RNA per unit of skeletal muscle protein to
assess the efficiency and capacity to synthesize proteins. To examine
the effect of age on the rate of muscle protein synthesis we will first
study 90 healthy subjects from three separate age groups20-30 yrs, 45-55
yrs and above 65 yrs. To determine the effect of resistance training on
muscle protein synthesis in middle-age and older subjects, we will
randomly assign 60 inactive middle-aged and older subjects to a 12-week
resistance training program or nonexercising control group and study
their muscle protein synthesis. These studies will provide new insights
into the mechanism of muscle wasting and the influence of resistance
training for use as a therapeutic intervention to reverse the age-related
decline in skeletal muscle protein synthesis.
StatusFinished
Effective start/end date4/15/938/31/15

Funding

  • National Institutes of Health: $151,100.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $694,484.00
  • National Institutes of Health: $569,313.00
  • National Institutes of Health: $535,799.00
  • National Institutes of Health
  • National Institutes of Health: $747,665.00
  • National Institutes of Health
  • National Institutes of Health: $567,177.00
  • National Institutes of Health
  • National Institutes of Health: $562,353.00
  • National Institutes of Health: $548,883.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $576,867.00
  • National Institutes of Health: $488,667.00
  • National Institutes of Health: $705,805.00
  • National Institutes of Health: $648,582.00
  • National Institutes of Health: $682,432.00
  • National Institutes of Health
  • National Institutes of Health: $584,386.00
  • National Institutes of Health: $690,347.00
  • National Institutes of Health

Fingerprint

Muscles
Muscle Proteins
Proteins
Resistance Training
Myosin Heavy Chains
Mitochondrial Proteins
Skeletal Muscle
Sarcopenia
Insulin-Like Growth Factor I
Myosins
Exercise
Muscle Mitochondrion
Protein Isoforms
Contractile Proteins
Mitochondrial Genes
Leucine
Mitochondrial DNA
Obesity
Biopsy
Phenylalanine

ASJC

  • Medicine(all)