| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY
Departments of 1Medicine and of 2Physiology, University of Wisconsin, Madison, Wisconsin 53706
Submitted 21 June 2004 ; accepted in final form 27 July 2004
Although a diminished ability of tissues and organisms to tolerate stress is a clinically important hallmark of normal aging, little is known regarding its biochemical basis. Our goal was to determine whether age-associated changes in AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism during the stress response, might contribute to the poor stress tolerance of aged cardiac and skeletal muscle. Basal AMPK activity and the degree of activation of AMPK by AMP and by in vivo hypoxemia (arterial PO2 of 39 mmHg) were measured in cardiac and skeletal muscle (gastrocnemius) from 5- and 24-mo-old C57Bl/6 mice. In the heart, neither basal AMPK activity nor its allosteric activation by AMP was affected by age. However, after 10 min of hypoxemia, the activity of 
2-AMPK, but not 1-AMPK, was significantly higher in the hearts from old than from young mice (P < 0.005), this difference being due to differences in phosphorylation of 2-AMPK. Significant activation of AMPK in the young hearts did not occur until 30 min of hypoxemia (P < 0.01), stress that was poorly tolerated by the old mice (mortality = 67%). In contrast, AMPK activity in gastrocnemius muscle was unaffected by age or hypoxemia. We conclude that the age-associated decline in hypoxic tolerance in cardiac and skeletal muscle is not caused by changes in basal AMPK activity or a blunted AMPK response to hypoxia. Activation of AMPK by in vivo hypoxia is slower and more modest than might be predicted from in vitro and ex vivo experiments.
senescence; ischemia; mouse; energetics
This article has been cited by other articles:
|
|
 |
|
  J. D. Mulligan, A. A. Gonzalez, A. M. Stewart, H. V. Carey, and K. W. Saupe Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse J. Physiol., April 15, 2007; 580(2): 677 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Al-Regaiey, M. M. Masternak, M. S. Bonkowski, J. A. Panici, J. J. Kopchick, and A. Bartke Effects of Caloric Restriction and Growth Hormone Resistance on Insulin-Related Intermediates in the Skeletal Muscle J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2007; 62(1): 18 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-H. Ning, S.-H. Chen, N. E. Buroker, C.-S. Xu, F.-R. Li, S.-P. Li, D.-S. Song, M. Ge, O. M. Hyyti, M. Zhang, et al. Short-cycle hypoxia in the intact heart: hypoxia-inducible factor 1{alpha} signaling and the relationship to injury threshold Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H333 - H341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Wadley, R. S. Lee-Young, B. J. Canny, C. Wasuntarawat, Z. P. Chen, M. Hargreaves, B. E. Kemp, and G. K. McConell Effect of exercise intensity and hypoxia on skeletal muscle AMPK signaling and substrate metabolism in humans Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E694 - E702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Hancock, E. Janssen, and R. L. Terjung Contraction-mediated phosphorylation of AMPK is lower in skeletal muscle of adenylate kinase-deficient mice J Appl Physiol, February 1, 2006; 100(2): 406 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Thomson and S. E. Gordon Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation J Appl Physiol, February 1, 2005; 98(2): 557 - 564. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
