Aging human muscle

Atrophy in aging human muscle description and new concepts... 

Such studies are numerous. They will not be reviewed in detail, partly because it is not certain which are directly relevant to the complex human problem. Because therapy forpatients is the ultimate goal, biochemical studies of aging human muscle would be relevant to understanding the pathogenesis of aging atrophy if, in the patients studied, the disorder is actually primary within their muscle fibers. But if the problem is caused by a dysinnerva-tion or denervation phenomenon, the essential trouble needing repair is located elsewhere, farther upstream in the motor unit. 

Having established that mtDNA somatic mutations, especially large-scale deletions, accumulate in aging human muscle, at least segmentally, and almost certainly beyond the pathogenic threshold within individual fibers, it follows that the respiratory chain function must also decline with time. Numerous papers, mostly published in the 1990s, have provided biochemical evidence of such a decline affecting one or more respiratory chain... 

Jozsi AC, Dupont-Versteegden BE, Taylor-Jones JM et al. (2000) Aged human muscle demonstrates an altered gene expression profile consistent with an impaired response to exercise. Meeh Ageing Dev 120, 45-56. 

There have been relatively few studies of age-related changes in tissue camosine levels despite the fact that the initial observation of the dipeptide s ability to suppress some features of senescence were made more than 15 years ago. Camosine levels have been reported to decline with age in the rats (Johnson and Hammer, 1992 Stuerenburg and Kunze, 1999) and human muscle (Stuerenburg and Kunze, 1999). More recently, Tallon et ah (2007) found evidence of camosine s age-related decline in human muscle fibers. 

L10. Lezza, A. M. S., Boffoli, D., Scacco, S., Cantatore, R, and Gadaleta, M. N., Correlation between mitochondrial DNA 4977-bp deletion and respiratory chain enzyme activities in aging human skeletal muscles. Biochem. Biophys. Res. Commun. 205, 772—779 (1994). 

Intracellular amyloid-p oligomers in s-IBM in s-IBM, ragged-red fibers are somewhat more abundant than in similarly aged non-IBM patients, and mitochondrial functional defects occur (see Chapters 7 and 10). From Askanas studies, the earliest identifiable pathogenic step in s-IBM is intracellular increase of amyloid-P oligomers, which are considered to be mitotoxic because their over-expression within cultured human muscle fibers produces mitochondrial abnormalities (see Chapters 7 and 10). 

Intended for general treatment of muscle-fiber atrophy in aging and in several other settings, anti-myostatins are being developed as a new approach, but they have not yet become established for clinical use in any human muscle atrophy. 

Pharmacological/blochemical substances without established value for human muscle atrophy of aging... 

Bua E, Johnson J, Herbst A et al. (2006) Mitochondrial DNA-deletion mutation accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am J Him Genet 79, 469 80. 

MelovS,ShoffnerJM,KaufmanAWallaceDC. (1995) Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle. Nucleic Acid Res 21, 4122 126. 

HseUi RH, Hou JH, Hsu HS, Wei YH. (1994) Age-dependent respiratory function decline and DNA deletions in human muscle mitochondria. Biochem Mol Biol Intern 32, 1009-1022. 

Human muscle protein metabolism in relation to exercise and aging potential therapeutic applications... 

Most cellular signaling data associated with protein turnover have been collected in Drosophila, cell lines, and rodents. In the forthcoming paragraphs we will briefly summarize the literature with the latest understanding of the ceUular and molecular mechanisms associated with human age-related muscle wasting in response to nutrition and exercise, then detail potential therapeutic interventions that may counteract age-related muscle loss. 

Welle S, Brooks AL Delehanty JM et al. (2003) Gene expression profile of aging in human muscle. Physiol Genomics 14, 149-159. 

Carey KA, Farnfield MM, Tarquinio SD et al. (2007) Impaired expression of Notch signaling genes in aged human skeletal muscle. J Gerontol A Biol Sd Med Sd 62, 9-17. 

Askanas V, BngelWK. (1998) Does overexpression of betaAPP in aging muscle have a pathogenic role and a relevance to Alzheimer s disease Clues from inclusion body myositis, cultured human muscle, and transgenic mice. Am J Pathol 153, 1673-1677. 

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