Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy
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Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy. / Suetta, Charlotte; Frandsen, Ulrik; Nielsen, Line; Jensen, Mette Munk; Jespersen, Jakob G; Hvid, Lars Grøndahl; Bayer, Monika; Petersson, Stine Juhl; Schrøder, Henrik D; Andersen, Jesper L.; Heinemeier, Katja M; Aagaard, Per; Schjerling, Peter; Kjaer, Michael.
I: P L o S One, Bind 7, Nr. 12, 2012, s. e51238.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy
AU - Suetta, Charlotte
AU - Frandsen, Ulrik
AU - Nielsen, Line
AU - Jensen, Mette Munk
AU - Jespersen, Jakob G
AU - Hvid, Lars Grøndahl
AU - Bayer, Monika
AU - Petersson, Stine Juhl
AU - Schrøder, Henrik D
AU - Andersen, Jesper L.
AU - Heinemeier, Katja M
AU - Aagaard, Per
AU - Schjerling, Peter
AU - Kjaer, Michael
PY - 2012
Y1 - 2012
N2 - Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1a and PGC-1ß (1-4 days) and a ~10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast, Akt phosphorylation was unchanged in old muscle after 2 days and increased after 4 days of immobilization. Further, an age-specific down-regulation of MuRF-1 and Atrogin-1 expression levels was observed following 2 weeks of immobilization, along with a slowing atrophy response in aged skeletal muscle. Neither the immediate loss of muscle mass, nor the subsequent age-differentiated signaling responses could be explained by changes in inflammatory mediators, apoptosis markers or autophagy indicators. Collectively, these findings indicate that the time-course and regulation of human skeletal muscle atrophy is age dependent, leading to an attenuated loss in aging skeletal muscle when exposed to longer periods of immobility-induced disuse.
AB - Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1a and PGC-1ß (1-4 days) and a ~10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast, Akt phosphorylation was unchanged in old muscle after 2 days and increased after 4 days of immobilization. Further, an age-specific down-regulation of MuRF-1 and Atrogin-1 expression levels was observed following 2 weeks of immobilization, along with a slowing atrophy response in aged skeletal muscle. Neither the immediate loss of muscle mass, nor the subsequent age-differentiated signaling responses could be explained by changes in inflammatory mediators, apoptosis markers or autophagy indicators. Collectively, these findings indicate that the time-course and regulation of human skeletal muscle atrophy is age dependent, leading to an attenuated loss in aging skeletal muscle when exposed to longer periods of immobility-induced disuse.
U2 - 10.1371/journal.pone.0051238
DO - 10.1371/journal.pone.0051238
M3 - Journal article
C2 - 23284670
VL - 7
SP - e51238
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 12
ER -
ID: 44383957