Sarcopenia and aging
Tim
Sarcopenia and aging.
Kamel HK.
Division of Geriatrics and Gerontology, Medical College of Wisconsin,
Milwaukee, WI, USA.
Sarcopenia refers to the gradual decline in muscle mass and quality
noted with advancing age. There is growing evidence linking sarcopenia
to functional disability, falls, decreased bone density, glucose
intolerance, and decreased heat and cold tolerance in older adults.
Factors implicated in the etiology of sarcopenia include decreased
physical activity, malnutrition, increased cytokine activity,
oxidative stress, and abnormalities in growth hormone and sex steroid
axes. At present, progressive resistance training is the best
intervention shown to slow down or reverse this condition. Preliminary
studies show that the utilization of several trophic factors, notably
testosterone and DHEA, may have a salutary effect on muscle mass
and/or strength in older adults. More research is needed, however,
before drawing definite conclusion as to the clinical utility of these
substances in the management of sarcopenia.
Publication Types:
Review
Review, Tutorial
PMID: 12822704 [PubMed - indexed for MEDLINE]
Matti Narkia
<6da4c14.04092...@posting.google.com> timo...@my-deja.com (Tim)
wrote:
Diet related mild chronic metabolic acidosis is common in western countries
and worsens with age due to age-related renal functional decline. Chronic
metabolic acidosis is known to cause muscle protein breakdown. Supplements
like potassium bicarbonate (KHCO3) neutralize metabolic acidosis and may
prevent continuing age-related loss of muscle mass and restore previously
accrued deficits.
Related references:
Frassetto L, Morris RC Jr, Sebastian A.
Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal
women.
J Clin Endocrinol Metab. 1997 Jan;82(1):254-9.
PMID: 8989270 [PubMed - indexed for MEDLINE]
<URL:http://jcem.endojournals.org/cgi/content/full/82/1/254>
"Previously we demonstrated that low grade chronic metabolic
acidosis exists normally in humans eating ordinary diets
that yield normal net rates of endogenous acid production
(EAP), and that the degree of acidosis increases with age.
We hypothesize that such diet-dependent and age-amplifying
low grade metabolic acidosis contributes to the decline in
skeletal muscle mass that occurs normally with aging. This
hypothesis is based on the reported finding that chronic
metabolic acidosis induces muscle protein breakdown, and
that correction of acidosis reverses the effect.
Accordingly, in 14 healthy postmenopausal women residing in
a General Clinical Research Center and eating a constant
diet yielding a normal EAP rate, we tested whether
correcting their "physiological" acidosis with orally
administered potassium bicarbonate (KHCO3; 60–120 mmol/day
for 18 days) reduces their urinary nitrogen loss. KHCO3
reduced EAP to nearly zero, significantly reduced the blood
hydrogen ion concentration (P < 0.001), and increased the
plasma bicarbonate concentration (P < 0.001), indicating
that pre-KHCO3, diet-dependent EAP was significantly
perturbing systemic acid-base equilibrium, causing a low
grade metabolic acidosis. Urinary ammonia nitrogen, urea
nitrogen, and total nitrogen levels significantly decreased.
The cumulative reduction in nitrogen excretion was 14.1 ±
12.3 g (P < 0.001). Renal creatinine clearance and urine
volume remained unchanged. We conclude that in
postmenopausal women, neutralization of diet-induced EAP
with KHCO3 corrects their preexisting diet-dependent low
grade metabolic acidosis and significantly reduces their
urinary nitrogen wasting. The magnitude of the KHCO3-induced
nitrogen-sparing effect is potentially sufficient to both
prevent continuing age-related loss of muscle mass and
restore previously accrued deficits."
Frassetto LA, Morris RC, Sebastian A.
Effect of age on blood acid-base composition in adult humans: role of
age-related renal functional decline.
Am J Physiol. 1996 Dec;271(6 Pt 2):F1114-22.
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8997384&dopt=Abstract>
"... Otherwise healthy adults manifest a low-grade diet-
dependent metabolic acidosis, the severity of which
increases with age at constant EAP, apparently due in part
to the normal age-related decline of renal function."
Frassetto L, Sebastian A.
Age and systemic acid-base equilibrium: analysis of published data.
J Gerontol A Biol Sci Med Sci. 1996 Jan;51(1):B91-9.
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8548506&dopt=Abstract>
"To investigate whether systemic acid-base equilibrium
changes with aging in normal adult humans, we reviewed
published articles reporting the acid-base composition of
arterial, arterialized venous, or capillary blood in age-
identified healthy subjects. We extracted or calculated
blood hydrogen ion concentration ([H+]), plasma bicarbonate
concentration ([HCO3(-)]), blood PCO2, and age, and computed
a total of 61 age-group means, distributed among eight 10-
year intervals from age 20 to 100 years. Using linear
regression analysis, we found that with increasing age,
there is a significant increase in the steady-state blood
[H+] (p < .001), and reduction in steady-state plasma
[HCO3(-)] (p < .001), indicative of a progressively
worsening low-level metabolic acidosis. Blood PCO2 decreased
with age (p < .05), in keeping with the expected respiratory
adaptation to metabolic acidosis. Such age-related
increasing metabolic acidosis may reflect in part the normal
decline of renal function with increasing age. The role of
age-related metabolic acidosis in the pathogenesis of the
degenerative diseases of aging warrants consideration."
Mitch WE, Medina R, Grieber S, May RC, England BK, Price SR, Bailey JL,
Goldberg AL.
Metabolic acidosis stimulates muscle protein degradation by activating the
adenosine triphosphate-dependent pathway involving ubiquitin and
proteasomes.
J Clin Invest. 1994 May;93(5):2127-33.
PMID: 8182144 [PubMed - indexed for MEDLINE]
<URL:http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=8182144>
"Metabolic acidosis often leads to loss of body protein due mainly to
accelerated protein breakdown in muscle.
[...]
These results are consistent with, but do not prove that
acidosis stimulates muscle proteolysis by activating the
ATP-ubiquitin-proteasome-dependent, proteolytic pathway."
May RC, Masud T, Logue B, Bailey J, England BK.
Metabolic acidosis accelerates whole body protein degradation and leucine
oxidation by a glucocorticoid-dependent mechanism.
Miner Electrolyte Metab. 1992;18(2-5):245-9.
PMID: 1465068 [PubMed - indexed for MEDLINE]
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1465068&dopt=Abstract>
"... We conclude that chronic metabolic acidosis accelerates
whole body protein turnover and reduces the efficiency of
protein utilization by accelerating amino acid oxidation.
These changes may require an intact glucocorticoid axis."
May RC, Masud T, Logue B, Bailey J, England B.
Chronic metabolic acidosis accelerates whole body proteolysis and oxidation
in awake rats.
Kidney Int. 1992 Jun;41(6):1535-42.
PMID: 1501410 [PubMed - indexed for MEDLINE]
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1501410&dopt=Abstract>
"... We conclude that chronic metabolic acidosis accelerates
whole body protein turnover and affects the reincorporation
of amino acid into body proteins by accelerating amino acid
oxidation."
May RC, Kelly RA, Mitch WE.
Metabolic acidosis stimulates protein degradation in rat muscle by a
glucocorticoid-dependent mechanism.
J Clin Invest. 1986 Feb;77(2):614-21.
PMID: 3511100 [PubMed - indexed for MEDLINE]
<URL:http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=3511100>
"... We conclude that chronic metabolic acidosis depresses
nitrogen utilization and increases glucocorticoid
production. The combination of increased glucocorticoids and
acidosis stimulates muscle proteolysis but does not affect
protein synthesis. These changes in muscle protein
metabolism may play a role in the defense against acidosis
by providing amino acid nitrogen to support the glutamine
production necessary for renal ammoniagenesis."
Williams B, Layward E, Walls J.
Skeletal muscle degradation and nitrogen wasting in rats with chronic
metabolic acidosis.
Clin Sci (Lond). 1991 May;80(5):457-62.
PMID: 1851685 [PubMed - indexed for MEDLINE]
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1851685&dopt=Abstract>
"1. Chronic metabolic acidosis is associated with impaired
growth and negative nitrogen balance, suggesting that it
promotes endogenous protein catabolism. 2. Skeletal muscle
is the major repository of body protein and is a potential
target for stimuli of protein catabolism. 3. This study in
vivo examines the effects of chronic metabolic acidosis on
the relationship between growth, nitrogen disposal and
skeletal muscle catabolism in the rat. 4. Growth, nitrogen
utilization and acquisition of body mass were significantly
impaired in acidotic animals compared with pair-fed
controls. 5. Total nitrogen excretion was significantly
increased in acidotic rats despite decreased urea
production. The time course of this response to acidosis was
synchronous with that of accelerated protein catabolism in
skeletal muscle. 6. It is proposed that metabolic acidosis
impairs growth by stimulating skeletal muscle protein
catabolism. It is suggested that this forms part of a co-
ordinated multi-organ homoeostatic response to acidosis,
skeletal muscle and down-regulated urea production supplying
the nitrogen required for renal ammoniagenesis."
Morris RC, Schmidlin O, Tanaka M, Forman A, Frassetto L, Sebastian A.
Differing effects of supplemental KCl and KHCO3: pathophysiological and
clinical implications.
Semin Nephrol. 1999 Sep;19(5):487-93. Review.
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10511388&dopt=Abstract>
Kurtz I, Maher T, Hulter HN, Schambelan M, Sebastian A.
Effect of diet on plasma acid-base composition in normal humans.
Kidney Int. 1983 Nov;24(5):670-80.
PMID: 6663989 [PubMed - indexed for MEDLINE]
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=6663989&dopt=Abstract>
Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris RC Jr.
Estimation of the net acid load of the diet of ancestral preagricultural
Homo sapiens and their hominid ancestors.
Am J Clin Nutr. 2002 Dec;76(6):1308-16.
PMID: 12450898 [PubMed - indexed for MEDLINE]
<URL:http://www.ajcn.org/cgi/content/full/76/6/1308>
"... Results: The mean (± SD) NEAP for 159 retrojected
preagricultural diets was -88 ± 82 mEq/d; 87% were net base-
producing. The computational model predicted NEAP for the
average American diet (as recorded in the third National
Health and Nutrition Examination Survey) as 48 mEq/d, within
a few percentage points of published measured values for
free-living Americans; the model, therefore, was not biased
toward generating negative NEAP values. The historical shift
from negative to positive NEAP was accounted for by the
displacement of high-bicarbonate-yielding plant foods in the
ancestral diet by cereal grains and energy-dense, nutrient-
poor foods in the contemporary diet—neither of which are net
base-producing.
Conclusions: The findings suggest that diet-induced
metabolic acidosis and its sequelae in humans eating
contemporary diets reflect a mismatch between the nutrient
composition of the diet and genetically determined
nutritional requirements for optimal systemic acid-base
status."
--
Matti Narkia
--
Matti Narkia