The purpose is to determine the mechanisms responsible for the increased susceptibility to and impaired recovery from contraction-induced injury of skeletal muscles in old animals compared with those in younger animals, and for the protection from contraction-induced injury provided by conditioning programs of pliometric (lengthening) contractions. Contraction-induced injury provided by conditioning programs of activated muscle fibers are stretched as opposed to shortened or held at fixed length. The magnitude of a contraction-induced injury is best predicted (r2 = 0.80) by the product of the length of the stretch and the concurrent average force developed. The injury is initiated by the mechanical disruption of the ultrastructure of small groups of sarcomeres. After repeated exposures to moderate protocols of pliometric contractions, muscles in animals of all ages become """"""""conditioned"""""""" and are no longer injured by protocols of pliometric contractions which previously caused injury. The working hypotheses are that: (i) contraction-induced injury occurs when weaker sarcomeres in series with stronger sarcomeres are stretched beyond overlap of thick and thin filaments and are damaged; and (ii) pliometric conditioning protects muscle fibers from contraction-induced injury by initiating injury to the weaker sarcomeres with subsequent replacement of weaker by stronger sarcomeres. Hypotheses will be tested through in vivo and in situ experiments on hind-limb muscles of specific pathogen free young (3 month), adult (12 month), and old (26 month) mice and in vitro experiments on single permeabilized fiber segments and single intact muscle fibers from mice, rats, and frogs. The clarification of the role of contraction-induced injury in the development of muscle atrophy and weakness that occurs with aging is of the utmost importance. Understanding the mechanisms responsible for the increased susceptibility to and impaired recovery from contraction-induced injury for muscles of old animals and for the protection provided to muscles by pliometric conditioning will facilitate the design of conditioning programs to protect muscles, particularly muscles of old people, from injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG006157-13
Application #
6029745
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Project Start
1986-05-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Physiology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Brooks, S V; Opiteck, J A; Faulkner, J A (2001) Conditioning of skeletal muscles in adult and old mice for protection from contraction-induced injury. J Gerontol A Biol Sci Med Sci 56:B163-71
Dennis, R G; Kosnik 2nd, P E; Gilbert, M E et al. (2001) Excitability and contractility of skeletal muscle engineered from primary cultures and cell lines. Am J Physiol Cell Physiol 280:C288-95
Lynch, G S; Hinkle, R T; Faulkner, J A (2001) Force and power output of diaphragm muscle strips from mdx and control mice after clenbuterol treatment. Neuromuscul Disord 11:192-6
Koh, T J; Brooks, S V (2001) Lengthening contractions are not required to induce protection from contraction-induced muscle injury. Am J Physiol Regul Integr Comp Physiol 281:R155-61
Brooks, S V; Faulkner, J A (2001) Severity of contraction-induced injury is affected by velocity only during stretches of large strain. J Appl Physiol 91:661-6
Dennis, R G; Kosnik 2nd, P E (2000) Excitability and isometric contractile properties of mammalian skeletal muscle constructs engineered in vitro. In Vitro Cell Dev Biol Anim 36:327-35
Lynch, G S; Hinkle, R T; Faulkner, J A (2000) Power output of fast and slow skeletal muscles of mdx (dystrophic) and control mice after clenbuterol treatment. Exp Physiol 85:295-9
Stevens, E D; Faulkner, J A (2000) The capacity of mdx mouse diaphragm muscle to do oscillatory work. J Physiol 522 Pt 3:457-66
McArdle, A; van der Meulen, J H; Catapano, M et al. (1999) Free radical activity following contraction-induced injury to the extensor digitorum longus muscles of rats. Free Radic Biol Med 26:1085-91

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