Mitochondrial DNA Deletion Mutations and Sarcopenia

Aiken, Judd M.; Bua, Entela; Cao, Zhengjin; Lopez, Marisol E.; Wanagat, Jonathan; McKenzie, Debbie; McKiernan, Susan H.

doi:10.1111/j.1749-6632.2002.tb02111.x

Cited by 79 publications

(50 citation statements)

References 20 publications

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“…28 In normal aging, the mtDNA mutations have been demonstrated to be associated with muscle fiber atrophy, and it has been postulated that mtDNA mutations are an important factor for development of sarcopenia in aging. 42,43 The mtDNA mutations in s-IBM muscle may thus contribute to muscle atrophy and weakness. Mitochondrial defects in s-IBM may also be due to other factors involved in the disease process.…”

Section: Mitochondrial Abnormalities In S-ibm Morphologic Alterationmentioning

confidence: 99%

Mitochondrial abnormalities in inclusion-body myositis

Oldfors¹,

Moslemi²,

Jonasson³

et al. 2006

Neurology

119

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Mitochondrial changes are frequently encountered in sporadic inclusion-body myositis (s-IBM). Cytochrome c oxidase (COX)-deficient muscle fibers and large-scale mitochondrial DNA (mtDNA) deletions are more frequent in s-IBM than in age-matched controls. COX deficient muscle fibers are due to clonal expansion of mtDNA deletions and point mutations in segments of muscle fibers. Such segments range from 75 microm to more than 1,000 microm in length. Clonal expansion of the 4977 bp "common deletion" is a frequent cause of COX deficient muscle fiber segments, but many other deletions also occur. The deletion breakpoints cluster in a few regions that are similar to what is found in human mtDNA deletions in general. Analysis in s-IBM patients of three nuclear genes associated with multiple mtDNA deletions, POLG1, ANT1 and C10orf2, failed to demonstrate any mutations. In s-IBM patients with high number of COX-deficient fibers, the impaired mitochondrial function probably contribute to muscle weakness and wasting. Treatment that has positive effects in mitochondrial myopathies may be tried also in s-IBM.

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Section: Mitochondrial Abnormalities In S-ibm Morphologic Alterationmentioning

confidence: 99%

Mitochondrial abnormalities in inclusion-body myositis

Oldfors¹,

Moslemi²,

Jonasson³

et al. 2006

Neurology

119

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“…This produces energetic deficit and hence atrophy of the fiber. The atrophic fiber becomes necrotic and is replaced by infiltrating connective and adipose tissues [10][11][12]. 2.…”

Section: Multifactorial Etiologymentioning

confidence: 99%

Sarcopenia: characteristics, genesis, remedies

et al. 2005

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The term sarcopenia is defined as the loss of mass and muscular function with age. It is characterized by a metabolic status in which the muscles present a reduced ability to produce and use energy. Thus, in humans between 20 and 80 years of age, muscle mass decreases about 40%, with negative effects on mobility, strength production, metabolic rate and respiratory function. A continuous reparative process is also present in skeletal muscle due to the presence of quiescent adult stem cells, called satellite cells, which are able to change their phenotype when appropriate conditions are present. Sarcopenia is considered an event with a multifactorial etiology: (1) mitochondrial deletion, i.e., replication errors in mitochondrial DNA that lead to an energetic deficit and fiber atrophy; (2) protein synthesis alterations, with an imbalance between protein degradation and the ability of the fibers to synthesize protein; (3) loss of repair ability of the satellite cells, caused by an alteration in the proteic growth factors (mainly IGF-1, mIGF-1, HGF) and hormones (growth hormone, testosterone and estrogens), or by an imbalance of the antioxidant system. We are still far from a complete understanding of the causes and characteristics of the sarcopenic process, and from a solution to the problem. However, a suitable lifestyle (programmed physical training) and a suitable diet (caloric restriction) seem to be the most effective therapeutic approaches in order to control at least the more alarming symptoms of sarcopenia.

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“…In some cases, mutated mitochondria may acquire replicative advantage over normal ones, which is consistent with the observation that in long-lived cells, such as myocytes, mitochondria with homoplasmic mtDNA mutations may completely displace normal mitochondria. 21,22,65 Although such accumulation of defective mitochondria theoretically can be attributed to their diminished autophagic removal 66 (see below), the role of preferential propagation (clonal expansion) of defective mitochondria was recently supported by the findings of homoplasmic mtDNA mutations in intestinal epithelium 67 and tumors. 68 In such rapidly proliferating cell systems, molecular damage is efficiently diluted, and autophagy may play only a minor role in mitochondrial turnover.…”

Section: Mitochondrial Agingmentioning

confidence: 96%