X-Message-Number: 25999
Date: Mon, 11 Apr 2005 05:24:32 -0700 (PDT)
From: Doug Skrecky <>
Subject: sarcopenia may be avoidable

[Dietary protein, leucine, resistance training, and vitamin D are good.
Creatine, estrogen, and growth hormone make no difference. Jury is out on
dehydroepiandrosterone, interleukin-6 and testosterone]

J Lab Clin Med. 2001 Apr;137(4):231-43.
Sarcopenia.
  Sarcopenia is a term utilized to define the loss of muscle mass
and strength that occurs with aging. Sarcopenia is believed to
play a major role in the pathogenesis of frailty and functional
impairment that occurs with old age. Progressive muscle wasting
occurs with aging. The prevalence of clinically significant
sarcopenia is estimated to range from 8.8% in young old women to
17.5% in old old men. Persons who are obese and sarcopenic (the
"fat frail") have worse outcomes than those who are sarcopenic
and non-obese. There is a disproportionate atrophy of type IIa
muscle fibers with aging. There is also evidence of an age-related
decrease in the synthesis rate of myosin heavy chain proteins, the
major anabolic protein. Motor units innervating muscle decline
with aging, and there is increased irregularity of muscle unit
firing. There are indications that cytokines-especially
interleukin-1beta, tumor necrosis factor-alpha, and
interleukin-6-play a role in the pathogenesis of sarcopenia.
Similarly, the decline in anabolic hormones-namely, testosterone,
dehydroepiandrosterone, growth hormone, and insulin-like growth
factor-I-is also implicated in the sarcopenic process. The role
of the physiologic anorexia of aging remains to be determined.
Decreased physical activity with aging appears to be the key
factor involved in producing sarcopenia. An increased research
emphasis on the factors involved in the pathogenesis of
sarcopenia is needed.

Age Ageing. 2004 Nov;33(6):548-55. Epub 2004 Sep 22.
Interventions for sarcopenia and muscle weakness in older people.
  OBJECTIVE: three major strategies have been tested for
combating the losses in muscle mass and strength that accompany
ageing. Those strategies are testosterone replacement for men,
growth hormone replacement and resistance exercise training.
This review will cover the risks and benefits associated with
each of these interventions. METHODS: searches of PubMed and Web
of Science through May 2004 yielded 85 relevant citations for
the following descriptors: sarcopenia, aging/ageing, elderly,
testosterone, hormone replacement, growth hormone, resistance
training, exercise, muscle mass, nutrition and strength. RESULTS
AND CONCLUSIONS: testosterone replacement in elderly hypogonadal
men produces only modest increases in muscle mass and strength,
which are observed in some studies and not in others. Higher
doses have not been given for fear of accelerating prostate
cancer. Growth hormone replacement in elderly subjects produces
a high incidence of side-effects, does not increase strength and
does not augment strength gains resulting from resistance
training. Some alternate strategies for stimulating the growth
hormone/insulin-like growth factor (IGF) pathway continue to
hold promise. The latter include growth hormone releasing hormone
(GHRH) and the complex of IGF-I with its major circulating
binding protein (IGF-I/IGFBP-3). Resistance training remains the
most effective intervention for increasing muscle mass and
strength in older people. Elderly people have reduced food intake
and increased protein requirements. As a result, adequate
nutrition is sometimes a barrier to obtaining full benefits from
resistance training in this population.

J Gerontol A Biol Sci Med Sci. 2003 May;58(5):M436-40.
Prevalence of sarcopenia and predictors of skeletal muscle mass
in nonobese women who are long-term users of estrogen-replacement
therapy.
  BACKGROUND: Sarcopenia refers to the loss of skeletal muscle
mass with age. We have found a prevalence of sarcopenia of 22.6%
in older postmenopausal women not receiving estrogen. The
objective of this study was to determine the prevalence of
sarcopenia in a population of older, nonobese, community-dwelling
women who had been long-term users of estrogen replacement
therapy (ERT). METHODS: We measured appendicular skeletal muscle
mass by dual x-ray absorptiometry (DXA) in 189 women aged 59 to
78 years old who had been using ERT for at least 2 years
(mean +/- SD duration, 12.7 +/- 8.2 years). We defined sarcopenia
as an adjusted appendicular skeletal muscle mass (ASM) (mass
divided by height squared) more than 2 SDs below the mean for a
young healthy reference population. Health and menopause history
were obtained. Body mass index (BMI) was calculated, and physical
activity and performance were measured using the Physical
Activity Scale in the Elderly, the chair rise time, the 6-minute
walk, and measures of lower extremity strength and power. Serum
estrone, estradiol, testosterone, and sex hormone binding
globulin were measured. RESULTS: The prevalence of sarcopenia in
nonobese, community-dwelling women who were long-term ERT users
was 23.8%. Skeletal muscle mass correlated significantly with
BMI, age at the time of starting ERT, hand grip strength, lower
extremity strength and power, and testosterone level, but not with
estradiol level. In linear regression analysis, BMI, leg press
strength, and testosterone level contributed to adjusted ASM,
accounting for 48.7% of the variance (p <.001). CONCLUSIONS:
Sarcopenia is as common in nonobese women who are long-term ERT
users as in community-dwelling women not using ERT, suggesting
that ERT does not protect against the muscle loss of aging. BMI,
strength, and testosterone level contributed to appendicular
skeletal mass in women. These data suggest that interventions to
target nutrition, strength training, and testosterone replacement
should be further investigated for their role in preventing
muscle loss with age.

Presse Med. 2002 Jul 27;31(25):1185-92.
Physical activity to delay the effects of aging on mobility
  SARCOPENIA: Aging is accompanied by the progressive reduction
in cardio-pulmonary capacity and muscular strength. These two
phenomena are partly related to the decrease in muscle mass, or
sarcopenia. CARDIO-PULMONARY CAPACITY: Measured by maximum oxygen
consumption (VO2max), it demonstrates the individual's capacity
for movement. It is also the principle marker of mortality due to
cardiovascular events. VO2max decreases by around 0.8% each year,
in close correlation with the evolution in muscle mass. These
phenomena are partly related to reduced physical activity and,
particularly, intense activity greater than 6 MET. Regular
practice of moderately intense physical activity can maintain
VO2max at a level 20 to 35% superior to that of the mean level
in the same age range, and is associated with increased autonomic
nervous system activity. DECREASED MUSCULAR STRENGTH: Sarcopenia
and the proportional decrease in fast-twitch muscle fibers are
related to a reduction in physical activity. The decrease in
muscular strength is a handicapping factor and increases the risk
of falls. Two sessions of training per week can increase by more
than 30% the strength of the muscles concerned, by increasing the
muscle volume and the maximum frequency of emission of motoneuron
influx. The production of somatotropin, insulin-like growth
factor-I and testosterone can also be increased. High-resistance
exercises are themselves sufficient to increase bone density. In
the light of these advantages, the practice of workouts in
endurance and strength should be encouraged.

J Am Coll Nutr. 2004 Dec;23(6 Suppl):601S-609S.
Protein nutrition, exercise and aging.
  Aging is associated with remarkable changes in body composition.
Loss of skeletal muscle, a process called sarcopenia, is a
prominent feature of these changes. In addition, gains in total
body fat and visceral fat content continue into late life. The
cause of sarcopenia is likely a result of a number of changes
that also occur with aging. These include reduced levels of
physical activity, changing endocrine function (reduced
testosterone, growth hormone, and estrogen levels), insulin
resistance, and increased dietary protein needs. Healthy
free-living elderly men and women have been shown to accommodate
to the Recommended Dietary Allowance (RDA) for protein of
0.8 g . kg(-1) . d(-1) with a continued decrease in urinary
nitrogen excretion and reduced muscle mass. While many elderly
people consume adequate amounts of protein, many older people
have a reduced appetite and consume less than the protein RDA,
likely resulting in an accelerated rate of sarcopenia. One
important strategy that counters sarcopenia is strength
conditioning. Strength conditioning will result in an increase
in muscle size and this increase in size is largely the result
of increased contractile proteins. The mechanisms by which the
mechanical events stimulate an increase in RNA synthesis and
subsequent protein synthesis are not well understood. Lifting
weight requires that a muscle shorten as it produces force
(concentric contraction). Lowering the weight, on the other hand,
forces the muscle to lengthen as it produces force (eccentric
contraction). These lengthening muscle contractions have been
shown to produce ultrastructural damage (microscopic tears in
contractile proteins muscle cells) that may stimulate increased
muscle protein turnover. This muscle damage produces a cascade
of metabolic events which is similar to an acute phase response
and includes complement activation, mobilization of neutrophils,
increased circulating an skeletal muscle interleukin-1,
macrophage accumulation in muscle, and an increase in muscle
protein synthesis and degradation. While endurance exercise
increases the oxidation of essential amino acids and increases
the requirement for dietary protein, resistance exercise results
in a decrease in nitrogen excretion, lowering dietary protein
needs. This increased efficiency of protein use may be important
for wasting diseases such as HIV infection and cancer and
particularly in elderly people suffering from sarcopenia.
Research has indicated that increased dietary protein intake
(up to 1.6 g protein . kg(-1) . d(-1)) may enhance the
hypertrophic response to resistance exercise. It has also been
demonstrated that in very old men and women the use of a
protein-calorie supplement was associated with greater strength
and muscle mass gains than did the use of placebo.

Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E645-53.
Combined ingestion of protein and free leucine with carbohydrate
increases postexercise muscle protein synthesis in vivo in male
subjects.
  The present study was designed to determine postexercise
muscle protein synthesis and whole body protein balance
following the combined ingestion of carbohydrate with or without
protein and/or free leucine. Eight male subjects were randomly
assigned to three trials in which they consumed drinks containing
either carbohydrate (CHO), carbohydrate and protein (CHO+PRO),
or carbohydrate, protein, and free leucine (CHO+PRO+Leu)
following 45 min of resistance exercise. A primed, continuous
infusion of L-[ring-13C6]phenylalanine was applied, with blood
samples and muscle biopsies collected to assess fractional
synthetic rate (FSR) in the vastus lateralis muscle as well as
whole body protein turnover during 6 h of postexercise recovery.
Plasma insulin response was higher in the CHO+PRO+Leu compared
with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%,
respectively, P < 0.05). Whole body protein breakdown rates were
lower, and whole body protein synthesis rates were higher, in the
CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial
(P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted
in a lower protein oxidation rate compared with the CHO+PRO trial.
Protein balance was negative during recovery in the CHO trial but
positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu
trial, whole body net protein balance was significantly greater
compared with values observed in the CHO+PRO and CHO trials
(P < 0.05). Mixed muscle FSR, measured over a 6-h period of
postexercise recovery, was significantly greater in the
CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006
vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with
intermediate values observed in the CHO+PRO trial (0.0820 +/-
0.0104%/h). We conclude that coingestion of protein and leucine
stimulates muscle protein synthesis and optimizes whole body
protein balance compared with the intake of carbohydrate only.

Am J Physiol Endocrinol Metab. 2005 Feb 22; [Epub ahead of print]
No effects of lifelong creatine supplementation on sarcopenia in
senescence-accelerated mice (SAMP8).
  Oral creatine supplementation can acutely ameliorate skeletal
muscle function in older humans, but its value in the prevention
of sarcopenia remains unknown. We evaluated the effects of
lifelong creatine supplementation on muscle mass and morphology,
contractility and metabolic properties in a mouse model of muscle
senescence. Male senescenceaccelerated mice (SAMP8) were fed
control or creatine-supplemented (2% of food intake) diet from
the age of 10 to 60 weeks. Soleus and EDL muscles were tested for
in vitro contractile properties, creatine content and morphology
at week 25 and 60. Both muscle types showed reduced
phosphocreatine content at week 60 that could not be prevented by
creatine. Accordingly, age-associated decline in muscle mass and
contractility was not influenced by treatment. Aged soleus muscles
had fewer and smaller fast-twitch glycolytic fibers irrespective
of treatment received. It is concluded that lifelong creatine
supplementation is no effective strategy to prevent sarcopenia
in senescence-accelerated mice.

Muscle Nerve. 2005 Apr;31(4):461-7.
Motor unit number estimates in the tibialis anterior muscle of
young, old, and very old men.
  The rate of motor unit (MU) loss and its influence on the
progression of sarcopenia is not well understood. Therefore, the
main purpose of this study was to estimate and compare numbers
of MUs in the tibialis anterior (TA) of young men
( approximately 25 years) and two groups of older men
( approximately 65 years and >/=80 years). Decomposition-enhanced
spike-triggered averaging was used to collect surface and
intramuscular electromyographic signals during isometric
dorsiflexions at 25% of maximum voluntary contraction. The mean
surface-MU potential size was divided into the maximum M wave to
calculate the motor unit number estimate (MUNE). The MUNE was
significantly reduced in the old (91) compared to young (150)
men, and further reduced in the very old men (59). Despite the
smaller MUNE at age 65, strength was not reduced until beyond 80
years. This suggests that age-related MU loss in the TA does not
limit function until a critical threshold is reached.

Age Ageing. 2004 Nov;33(6):548-55. Epub 2004 Sep 22
Interventions for sarcopenia and muscle weakness in older people.
  OBJECTIVE: three major strategies have been tested for combating
the losses in muscle mass and strength that accompany ageing.
Those strategies are testosterone replacement for men, growth
hormone replacement and resistance exercise training. This review
will cover the risks and benefits associated with each of these
interventions. METHODS: searches of PubMed and Web of Science
through May 2004 yielded 85 relevant citations for the following
descriptors: sarcopenia, aging/ageing, elderly, testosterone,
hormone replacement, growth hormone, resistance training, exercise,
muscle mass, nutrition and strength. RESULTS AND CONCLUSIONS:
testosterone replacement in elderly hypogonadal men produces only
modest increases in muscle mass and strength, which are observed
in some studies and not in others. Higher doses have not been
given for fear of accelerating prostate cancer. Growth hormone
replacement in elderly subjects produces a high incidence of
side-effects, does not increase strength and does not augment
strength gains resulting from resistance training. Some alternate
strategies for stimulating the growth hormone/insulin-like growth
factor (IGF) pathway continue to hold promise. The latter include
growth hormone releasing hormone (GHRH) and the complex of IGF-I
with its major circulating binding protein (IGF-I/IGFBP-3).
Resistance training remains the most effective intervention for
increasing muscle mass and strength in older people. Elderly
people have reduced food intake and increased protein
requirements. As a result, adequate nutrition is sometimes a
barrier to obtaining full benefits from resistance training in
this population.

Mol Aspects Med. 2005 Jun;26(3):203-19
Vitamin D in the aging musculoskeletal system: An authentic
strength preserving hormone.
  Until recently, vitamin D was only considered as one of the
calciotrophic hormones without major significance in other
metabolic processes in the body. Several recent findings have
demonstrated that vitamin D plays also a role as a factor for
cell differentiation, function and survival. Two organs, muscle
and bone, are significantly affected by the presence, or
absence, of vitamin D. In bone, vitamin D stimulates bone
turnover while protecting osteoblasts of dying by apoptosis
whereas in muscle vitamin D maintains the function of type II
fibers preserving muscle strength and preventing falls.
Furthermore, two major changes associated to aging: osteoporosis
and sarcopenia, have been also linked to the development of
frailty in elderly patients. In both cases vitamin D plays an
important role since the low levels of this vitamin seen in
senior people may be associated to a deficit in bone formation
and muscle function. In this review, the interaction between
vitamin D and the musculoskeletal components of frailty are
considered from the basic mechanisms to the potential therapeutic
approach. We expect that these new considerations about the
importance of vitamin D in the elderly will stimulate an
innovative approach to the problem of falls and fractures which
constitutes a significant burden to public health budgets worldwide

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