HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/5/R1270    most recent 00409.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Gonzalez, A. A. Articles by Saupe, K. W. Search for Related Content PubMed PubMed Citation Articles by Gonzalez, A. A. Articles by Saupe, K. W.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Effects of aging on cardiac and skeletal muscle AMPK activity: basal activity, allosteric activation, and response to in vivo hypoxemia in mice

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:

				G. R. Steinberg and B. E. Kemp AMPK in Health and Disease Physiol Rev, July 1, 2009; 89(3): 1025 - 1078. [Abstract] [Full Text] [PDF]

				K. A. Zwetsloot, L. M. Westerkamp, B. F. Holmes, and T. P. Gavin AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise J. Physiol., December 15, 2008; 586(24): 6021 - 6035. [Abstract] [Full Text] [PDF]

				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]