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Aerobic
Exercise Overcomes Age-Related Insulin Resistance Principal Investigator:
Satoshi Fujita, Ph.D.
Age-dependent loss of skeletal muscle mass and strength diminishes quality
of life of older individuals by impairing gait and increasing risks for
falls. An important contributing factor is reduced response of skeletal
muscle to anabolic hormones such as insulin. Physiological levels of insulin
stimulate synthesis of skeletal muscle in young adults only if blood flow
and amino acid availability are maintained. Insulin exerts a positive
anabolic effect on muscle in part through its ability to dilate blood
vessels and increase blood flow. With aging this ability of muscle to
respond to insulin is compromised, thereby diminishing insulin-induced
promotion of muscle protein synthesis. Aerobic exercise has been shown to
increase dilation of blood vessels and improve blood flow to the muscle. The
hypothesis of this study was that a bout of aerobic exercise before
administration of insulin would improve blood flow to the muscle brought on
by exercise in older individuals, and amplify the positive anabolic effect
of insulin on muscle protein synthesis.
Thirteen healthy, older subjects (67-69 years of age, 10 men and 3 women)
were randomly assigned to either an exercise group, which underwent 45
minutes of treadmill at 70% of the maximum heart rate, or a no-exercise
group. Both groups were infused intravenously with insulin and blood and
muscle biopsy samples were obtained for assessing muscle protein synthesis.
The results showed for the first time that a single bout of moderate aerobic
exercise restores insulin responsive muscle protein synthesis in elderly
individuals. The mechanism of this effect was shown to be from vasodilation,
improvement of blood flow and amino acid availability, and enhanced
activation of the Akt/mTOR signaling pathway, which is a pathway
specifically involved in protein synthesis. Thus moderate-intensity aerobic
exercise may be an effective intervention to counter age-related declines in
muscle mass and function and frailty.
Publication:
1. Fujita S, Rasmussen BB, Cadenas JG P, U Drummond MJUPU, Glynn ELUPUUP,
Sattler FR, and Volpi E. Aerobic exercise overcomes the age-related insulin
resistance of muscle protein metabolism by improving endothelial function
Uand Akt/mTOR signaling. Diabetes. 2007 56:1615-1622.
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Androgen Therapy in Older Women
Principal Investigator: Melinda Sheffield-Moore, Ph.D.
Aging can result in a progressive decline in skeletal muscle mass and
function. Reasons for this loss may include inadequate nutrition, hormonal
alterations, reduced mitochondrial protein synthesis, DNA alterations and
physical inactivity, all leading to an imbalance between protein synthesis
and breakdown. The decrease in muscle mass that characterizes the aging
process in both men and women is accompanied by a progressive increase in
fat tissue. As a result of the continued growth of our aging population, it
has become increasingly important to understand the mechanisms underlying
loss of muscle mass and function and devise interventions that can
ameliorate this loss. Androgen administration has been shown to positively
influence muscle protein synthesis in aging men, and has been used recently
by clinicians to improve muscle strength and function. Anabolic hormones
such as testosterone and oxandrolone improve lean body mass and strength in
both young and older men. Testosterone has limited potential in women
because of its virilizing effects. However, oxandrolone is purported to
induce fewer androgenic side effects, and may be useful in both sexes.
Numerous clinical trials have demonstrated its benefits in a multitude of
patient populations, including those with burn injuries and AIDS. However,
the potential benefits of oxandrolone administration have not previously
been examined in older women.
To address this issue, five healthy women between the ages of 63 and 67
years and seven older men, as matching controls, were studied. Oxandrolone
was administered orally at 7.5 and 10.5 mg doses twice daily for 15 days.
Metabolic parameters were measured at baseline (day 0), day 5 and day 14 of
oxandrolone administration. At these time points blood samples and muscle
biopsies were taken to measure muscle protein synthesis.
The results indicate that muscle protein synthesis increased in both older
women and men after 14 days of oxandrolone administration. However, the time
course of protein anabolism differed in men and women, since the rate
increased significantly in women only after 14 days, whereas protein
synthesis increased significantly in men at day 5 and then declined somewhat
by day 14. This decline is not unexpected since it is known that oxandrolone
administration significantly decreases testosterone production by day 5 in
older men. The results also indicated that the mechanism of increased muscle
mass in both older women and men is through increase in protein synthesis
rather than an inhibition of protein breakdown, since the rate of protein
breakdown remained unchanged.
The ability of an anabolic agent to reverse the loss of lean body mass using
an oral anabolic agent has considerable clinical implications. Given that
most trauma and burn patients have acute muscle wasting and most cancer and
AIDS patients show a chronic muscle wasting, such interventions may prove
useful in restoring muscle mass in these patient populations.
Publication:
1. Sheffield-Moore M, Paddon-Jones D, Casperson SL, Gilkison C, Volpi E,
Wolfe SE, Jiang J, Rosenblatt JI, Urban RJ. Androgen therapy induces muscle
protein anabolism in older women. J Clin Endocrinol Metab. 2006 91(10):
3844-9
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