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OAIC Completed Study Excitation-Contraction Coupling in Aging Muscle The long-term goal of this study is to elucidate the mechanism(s) responsible for the decline in skeletal muscle performance with age and non-pharmacological interventions. Our goals can be summarized as follows: - to determine the amount of DHPRs expression in isolated fast-twitch EDL muscle fiber from young, middle-aged, and old Fisher 344BNX rats,
- to assess whether reductions in the sarcoplasmic reticulum calcium release are the result of significant numbers of calcium release channels (RYRs) being uncoupled from DHPRs in older animals,
- to correlate the decline in skeletal muscle contraction properties with alterations in intracellular calcium concentrations, and
- to determine whether chronic caloric restriction prevents age-related changes in fiber calcium concentration, number of DHPR, and contraction force.
In the last 12 months, we have demonstrated and published that the specific force in single intact muscle fibers declines with age. We have also demonstrated that single fast- and slow-twitch fiber endurance are increased in muscles from aging rodents and that the nuclear transcription of proteins involved in excitation-contraction coupling is impaired in aging skeletal muscle. The project lists a total of 36 papers (30 published in peer-reviewed journals, 1 book, 1 paper under review and 4 papers in preparation). Peer Reviewed Publications from Aging Muscle Study: | Books/Book Chapters - Loeser R, Delbono O: Aging and the musculoskeletal system. In Principles of Geriatric Medicine and Gerontology. Hazzard WR, Blass J, Ettinger WH, Jr., Halter J, Ouslander JG, Eds. New York, McGraw-Hill, 1999, p. 1097-1111
Journal Articles - Gonzalez E, Delbono O: Recovery from fatigue in fast and slow single intact skeletal muscle fibers from aging mouse. Muscle Nerve 24:1219-1224, 2001
- Gonzalez E, Delbono O: Age-dependent fatigue in single intact fast- and slow fibers from mouse EDL and soleus skeletal muscles. Mech.Ageing Dev. 122:1019-1032, 2001
- Zheng Z, Messi ML, Delbono O: Age-dependent IGF-1 regulation of gene transcription of Ca2+ channels in skeletal muscle. Mech.Ageing Dev. 122:373-384, 2001
- Zheng Z, Delbono O: Promoter cloning and transcriptional regulation of the skeletal muscle DHPR a1s subunit. J Physiology In press: 2001
- Delbono O: Regulation of excitation contraction coupling by insulin-like growth factor-1 in aging skeletal muscle. J.Nutr.Health Aging 4:162-164, 2000
- Gonzalez E, Messi ML, Delbono O: The specific force of single intact extensor digitorum longus and soleus mouse muscle fibers declines with aging. J.Membr.Biol. 178:175-183, 2000
- Wang ZM, Messi ML, Delbono O: L-Type Ca(2+) channel charge movement and intracellular Ca(2+) in skeletal muscle fibers from aging mice. Biophys.J. 78:1947-1954, 2000
- Renganathan M, Wang ZM, Messi ML, Delbono O: Calcium regulates L-type Ca2+ channel expression in rat skeletal muscle cells. Pflugers Arch. 438:649-655, 1999
- Wang ZM, Messi ML, Delbono O: Patch-clamp recording of charge movement, Ca(2+) current, and Ca(2+) transients in adult skeletal muscle fibers. Biophys.J. 77:2709-2716, 1999
- Wang ZM, Messi ML, Renganathan M, Delbono O: Insulin-like growth factor-1 enhances rat skeletal muscle charge movement and L-type Ca2+ channel gene expression. J.Physiol 516:331-341, 1999
- Mayhew M, Renganathan M, Delbono O: Effectiveness of caloric restriction in preventing age-related changes in rat skeletal muscle . Biochem.Biophys.Res.Commun. 251:95-99, 1998
- Molinari EJ, Delbono O, Messi ML, Renganathan M, Arneric SP, Sullivan JP, Gopalakrishnan M: Up-regulation of human alpha7 nicotinic receptors by chronic treatment with activator and antagonist ligands. Eur.J.Pharmacol. 347:131-139, 1998
- Renganathan M, Messi ML, Delbono O: Overexpression of IGF-1 exclusively in skeletal muscle prevents age-related decline in the number of dihydropyridine receptors. J.Biol.Chem. 273:28845-28851, 1998
- Renganathan M, Delbono O: Caloric restriction prevents age-related decline in skeletal muscle dihydropyridine receptor and ryanodine receptor expression. FEBS Lett. 434:346-350, 1998
- Delbono O, Gopalakrishnan M, Renganathan M, Monteggia LM, Messi ML, Sullivan JP: Activation of the recombinant human alpha 7 nicotinic acetylcholine receptor significantly raises intracellular free calcium. J Pharmacol.Exp.Ther. 280:428-438, 1997
- Delbono O, Renganathan M, Messi ML: Excitation-Ca2+ release-contraction coupling in single aged human skeletal muscle fiber. Muscle Nerve Suppl 5:S88-92.:S88-S92, 1997
- Delbono O, Renganathan M, Messi ML: Regulation of mouse skeletal muscle L-type Ca2+ channel by insulin-like growth factor-1 activation. Biochem.Biophys.Res.Commun. 235:748-789, 1997
- Delbono O, Renganathan M, Messi ML: Regulation of mouse skeletal muscle L-type Ca2+ channel by activation of the insulin-like growth factor-1 receptor. J Neurosci. 17:6918-6928, 1997
- Delbono O, Reganathan M, Messi ML: Excitation-sarcoplasmic reticulum release-contraction coupling in single aged human skeletal muscle fiber. Muscle Nerve 19:861-869, 1997
- Messi ML, Renganathan M, Grigorenko E, Delbono O: Activation of alpha7 nicotinic acetylcholine receptor promotes survival of spinal cord motoneurons. FEBS Lett. 411:32-38, 1997
- Renganathan M, Messi ML, Delbono O: Dihydropyridine receptor-ryanodine receptor uncoupling in aged skeletal muscle. J.Membr.Biol. 157:247-253, 1997
- Renganathan M, Messi ML, Schwartz R, Delbono O: Overexpression of hIGF-1 exclusively in skeletal muscle increases the number of dihydropyridine receptors in adult transgenic mice. FEBS Lett. 417:13-16, 1997
- Renganathan M, Sonntag WE, Delbono O: L-type Ca2+ channel-insulin-like growth factor-1 receptor signaling impairment in aging rat skeletal muscle. Biochem.Biophys.Res.Commun. 235:784-789, 1997 Year 1996
- Delbono O, Meissner G: Sarcoplasmic reticulum Ca2+ release in rat slow- and fast-twitch muscles. J Membr.Biol. 151:123-130, 1996 Year 1995
- Delbono O, O'Rourke KS, Ettinger WH: Excitation-contraction uncoupling in aged single human skeletal muscle fibers. J Membr.Biol. 148:211-222, 1995
- Delbono O, O'Rourke KS, Ettinger WH: Excitation-calcium release uncoupling in aged single human skeletal muscle fibers. J Membr.Biol. 148:211-222, 1995
- Delbono O: Ca2+ modulation of sarcoplasmic reticulum Ca2+ release in rat skeletal muscle fibers. J Membr.Biol. 146:91-99, 1995
- Delbono O: Calcium modulation of sarcoplasmic reticulum calcium release in mammalian skeletal muscle fibers. J Membr.Biol. 146:91-99, 1995
- Delbono O, Chu A: Ca2+ release channels in rat denervated skeletal muscles. Exp.Physiol 80:561-574, 1995
- Mosier DR, Baldelli P, Delbono O, Smith RG, Alexianu ME, Appel SH, Stefani E: Amyotrophic lateral sclerosis immunoglobulins increase Ca2+ currents in a motoneuron cell line. Ann.Neurol. 37:102-109, 1995
| Publications under Review from Aging Muscle Study: | - Wang, Z. M., Messi, M. L., and Delbono, O. Sustained over expression of IGF-1 prevents age-dependent decrease in charge movement and intracellular calcium in mouse skeletal muscle.
| Publications in Preparation from Aging Muscle Study: | - Delbono, O. The use of single muscle fiber preparation to elucidate the mechanisms of sarcopenia.
- specific force and intracellular calcium in transgenic mice.
- Messi, M. L. and Delbono, O. Role of denervation in sarcopenia.
- Zheng, Z., Wang, Z. M., and Delbono, O. Transcriptional regulation of the mouse L-type calcium channel alpha1s subunit.
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