PMID:16373446

Citation	Haddad, F and Adams, GR (2006) Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophy. J. Appl. Physiol. 100:1188-203
Abstract	Sarcopenia is an age-related loss of muscle mass and strength. The aged can increase various measures of muscle size and strength in response to resistance exercise (RE), but this may not normalize specific tension. In rats, aging reduces the hypertrophy response and impairs regeneration. In this study, we measured cellular and molecular markers, indicative of muscle hypertrophy, that also respond to acute increases in loading. Comparing 6- and 30-mo-old rats, the aims were to 1) determine whether these markers are altered with age and 2) identify age-sensitive responses to acute RE. The muscles of old rats exhibited sarcopenia involving a deficit in contractile proteins and decreased force generation. The RNA-to-protein ratio was higher in the old muscles, suggesting a decrease in translational efficiency. There was evidence of reduced signaling via components downstream from the insulin/insulin-like growth factor (IGF)-I receptors in old muscles. The mRNA levels of myostatin and suppressor of cytokine signaling 2, negative regulators of muscle mass, were lower in old muscles but did not decrease following RE. RE induced increases in the mRNAs for IGF-I, mechano-growth factor, cyclin D1, and suppressor of cytokine signaling 3 were similar in old and young muscles. RE induced phosphorylation of the IGF-I receptor, and Akt increased in young but not old muscles, whereas that of S6K1 was similar for both. The results of this study indicate that a number of components of intracellular signaling pathways are sensitive to age. As a result, key anticatabolic responses appear to be refractory to the stimuli provided by RE.
Links	PubMed Online version:10.1152/japplphysiol.01227.2005
Keywords	Aging/metabolism; Aging/pathology; Animals; Gene Expression Regulation; Hypertrophy; Insulin Receptor Substrate Proteins; Insulin-Like Growth Factor I/genetics; Insulin-Like Growth Factor I/metabolism; Male; Muscle, Skeletal/metabolism; Muscle, Skeletal/pathology; Myostatin; Phosphoproteins/metabolism; Phosphorylation; Physical Conditioning, Animal; Proto-Oncogene Proteins c-akt/metabolism; RNA, Messenger/metabolism; Rats; Rats, Inbred BN; Rats, Inbred F344; Receptor, IGF Type 1/metabolism; Signal Transduction; Suppressor of Cytokine Signaling Proteins/genetics; Suppressor of Cytokine Signaling Proteins/metabolism; Time Factors; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:IRS1	involved_in	GO:0007568: aging	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

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