Limits...
Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy.

Suetta C, Frandsen U, Jensen L, Jensen MM, Jespersen JG, Hvid LG, Bayer M, Petersson SJ, Schrøder HD, Andersen JL, Heinemeier KM, Aagaard P, Schjerling P, Kjaer M - PLoS ONE (2012)

Bottom Line: 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-1α and PGC-1β (1-4 days) and a ~10% decrease in myofiber size (4 days).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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Sports Medicine and Center for Healthy Aging, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark. csuetta@gmail.com

ABSTRACT
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-1α and PGC-1β (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.

Show MeSH

Related in: MedlinePlus

Immobility-induced skeletal muscle atrophy causes an age-specific decline in muscle size.A. Scheme of experimental setup, including the time points of muscle biopsy procedure. B. Percentage decreases in muscle size (mean muscle fiber area) after 4 days of immobility in young (n = 11) and old (n = 9) as well as after 14 days of immobilization in young (n = 11) and old (n = 12), respectively. * Time effect, p<0.05 compared to pre, # Age effect, p<0.05 young compared to old within time point. Group mean data ± SEM. Mean myofiber area was assessed in the quadriceps femoris muscle, by muscle biopsy sampling. C. Muscle histology from resting state (pre) and immobility (14 d) was analyzed by myofibrillar ATPase at pH 10.3 preincubations demonstrating type I (white) and type II muscle fibers (black) [52].
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3526599&req=5

pone-0051238-g001: Immobility-induced skeletal muscle atrophy causes an age-specific decline in muscle size.A. Scheme of experimental setup, including the time points of muscle biopsy procedure. B. Percentage decreases in muscle size (mean muscle fiber area) after 4 days of immobility in young (n = 11) and old (n = 9) as well as after 14 days of immobilization in young (n = 11) and old (n = 12), respectively. * Time effect, p<0.05 compared to pre, # Age effect, p<0.05 young compared to old within time point. Group mean data ± SEM. Mean myofiber area was assessed in the quadriceps femoris muscle, by muscle biopsy sampling. C. Muscle histology from resting state (pre) and immobility (14 d) was analyzed by myofibrillar ATPase at pH 10.3 preincubations demonstrating type I (white) and type II muscle fibers (black) [52].

Mentions: In the present manuscript results from two human intervention studies are reported. At first, myofiber atrophy was induced for a period of 2 weeks to investigate the signaling pathways regulating disuse skeletal muscle atrophy in young and aged individuals, respectively (Figure 1). Muscle biopsies of the vastus lateralis muscle were collected prior to the intervention and immediately after cast removal. In order to study the time-course and identify signaling pathways involved in the initiation of disuse muscle atrophy, two additional groups of young and aged individuals were recruited and immobility was induced for 4 days. These subjects were biopsied after 24 h (∼1 d), 48 h (∼2 d) and 96 h (∼4 d) of immobility (Figure 1A). Within age groups, subjects recruited for the two immobilization protocols did not differ with respect to age, weight, BMI and activity level (Table S1).


Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy.

Suetta C, Frandsen U, Jensen L, Jensen MM, Jespersen JG, Hvid LG, Bayer M, Petersson SJ, Schrøder HD, Andersen JL, Heinemeier KM, Aagaard P, Schjerling P, Kjaer M - PLoS ONE (2012)

Immobility-induced skeletal muscle atrophy causes an age-specific decline in muscle size.A. Scheme of experimental setup, including the time points of muscle biopsy procedure. B. Percentage decreases in muscle size (mean muscle fiber area) after 4 days of immobility in young (n = 11) and old (n = 9) as well as after 14 days of immobilization in young (n = 11) and old (n = 12), respectively. * Time effect, p<0.05 compared to pre, # Age effect, p<0.05 young compared to old within time point. Group mean data ± SEM. Mean myofiber area was assessed in the quadriceps femoris muscle, by muscle biopsy sampling. C. Muscle histology from resting state (pre) and immobility (14 d) was analyzed by myofibrillar ATPase at pH 10.3 preincubations demonstrating type I (white) and type II muscle fibers (black) [52].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526599&req=5

pone-0051238-g001: Immobility-induced skeletal muscle atrophy causes an age-specific decline in muscle size.A. Scheme of experimental setup, including the time points of muscle biopsy procedure. B. Percentage decreases in muscle size (mean muscle fiber area) after 4 days of immobility in young (n = 11) and old (n = 9) as well as after 14 days of immobilization in young (n = 11) and old (n = 12), respectively. * Time effect, p<0.05 compared to pre, # Age effect, p<0.05 young compared to old within time point. Group mean data ± SEM. Mean myofiber area was assessed in the quadriceps femoris muscle, by muscle biopsy sampling. C. Muscle histology from resting state (pre) and immobility (14 d) was analyzed by myofibrillar ATPase at pH 10.3 preincubations demonstrating type I (white) and type II muscle fibers (black) [52].
Mentions: In the present manuscript results from two human intervention studies are reported. At first, myofiber atrophy was induced for a period of 2 weeks to investigate the signaling pathways regulating disuse skeletal muscle atrophy in young and aged individuals, respectively (Figure 1). Muscle biopsies of the vastus lateralis muscle were collected prior to the intervention and immediately after cast removal. In order to study the time-course and identify signaling pathways involved in the initiation of disuse muscle atrophy, two additional groups of young and aged individuals were recruited and immobility was induced for 4 days. These subjects were biopsied after 24 h (∼1 d), 48 h (∼2 d) and 96 h (∼4 d) of immobility (Figure 1A). Within age groups, subjects recruited for the two immobilization protocols did not differ with respect to age, weight, BMI and activity level (Table S1).

Bottom Line: 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-1α and PGC-1β (1-4 days) and a ~10% decrease in myofiber size (4 days).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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Sports Medicine and Center for Healthy Aging, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark. csuetta@gmail.com

ABSTRACT
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-1α and PGC-1β (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.

Show MeSH
Related in: MedlinePlus