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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
44
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pubmed:dateCreated |
1998-12-1
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pubmed:abstractText |
Excitation-contraction uncoupling has been identified as a mechanism underlying skeletal muscle weakness in aging mammals (sarcopenia). The basic mechanism for excitation-contraction uncoupling is a larger number of ryanodine receptors (RyR1) uncoupled to dihydropyridine receptors (DHPRs) (Delbono, O., O'Rourke, K. S., and Ettinger, W. H. (1995) J. Membr. Biol. 148, 211-222). In the present study, we used transgenic mice overexpressing human insulin-like growth factor-1 exclusively in skeletal muscle to test the hypothesis that a high concentration of IGF-1 prevents age-related decreases in DHPR number and in muscle force. Transgenic mice express 10-20-fold higher IGF-1 concentrations than nontransgenic mice at all ages (1-24 months). The number of DHPRs is 50-100% higher, and the DHPR/RyR1 ratio is 40% higher in transgenic soleus (predominantly type I fiber muscles), extensor digitorum longus (predominantly type II fiber muscles), and the pool of type I and type II fiber muscles than in nontransgenic young (6 months), adult (12 months), and old (24 months) mice. Furthermore, no age-related changes in DHPRs and the DHPR/RyR1 ratio were observed in transgenic muscles. The specific single twitch and tetanic muscle force in old transgenic soleus and extensor digitorum longus muscles are 50% higher than in old nontransgenic muscles. Taken together, these results support the concept that IGF-1- dependent prevention of age-related decline in DHPR expression is associated with stronger muscle contraction in older transgenic mice.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, L-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine Receptor Calcium Release...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28845-51
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9786885-Aging,
pubmed-meshheading:9786885-Animals,
pubmed-meshheading:9786885-Calcium Channels,
pubmed-meshheading:9786885-Calcium Channels, L-Type,
pubmed-meshheading:9786885-Humans,
pubmed-meshheading:9786885-Insulin-Like Growth Factor I,
pubmed-meshheading:9786885-Mice,
pubmed-meshheading:9786885-Mice, Transgenic,
pubmed-meshheading:9786885-Muscle, Skeletal,
pubmed-meshheading:9786885-Ryanodine Receptor Calcium Release Channel
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pubmed:year |
1998
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pubmed:articleTitle |
Overexpression of IGF-1 exclusively in skeletal muscle prevents age-related decline in the number of dihydropyridine receptors.
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pubmed:affiliation |
Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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