A Mutation in the Myostatin Gene Increases Muscle Mass and Enhances Racing Performance in Heterozygote Dogs

Mosher, Dana S.; Quignon, Pascale; Bustamante, Carlos D.; Sutter, Nathan B.; Mellersh, Cathryn S.; Parker, Heidi G.; Ostrander, Elaine A.

doi:10.1371/journal.pgen.0030079

Cited by 682 publications

(480 citation statements)

References 28 publications

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“…1997; Mosher et al. 2007). However, here, we show that total myostatin only moderately differs in a model of successful aging, suggesting the role of myostatin may not be as important in successful aging as other factors reported here.…”

Section: Discussionmentioning

confidence: 99%

Lifelong exercise, but not short-term high-intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation

et al. 2017

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Lifelong exercise is associated with regulation of skeletal mass and function, reductions in frailty, and successful aging. Yet, the influence of exercise on myostatin and myostatin‐interacting factors is relatively under examined in older males. Therefore, we investigated whether serum total myostatin, free myostatin, follistatin, and growth and differentiation factor 11 (GDF11) were altered following high‐intensity interval training (HIIT) in a group of 13 lifelong sedentary (SED; 64 [6] years) and 11 lifelong exercising (LEX; 62 [6] years) older males. SED follistatin was moderately greater than LEX pre‐HIIT (Cohen's d = 0.66), and was largely greater post‐HIIT (Cohen's d = 1.22). The HIIT‐induced increase in follistatin was large in SED (Cohen's d = 0.82) and absent in LEX (Cohen's d = 0.03). GDF11 was higher in LEX pre‐HIIT (Cohen's d = 0.49) and post‐HIIT (Cohen's d = 0.63) compared to SED. HIIT resulted in no change to GDF11 in LEX or SED (Cohen's d = 0.00–0.03). Peak power output and GDF11 were correlated (r = 0.603), independent of grouping. Differences in GDF11 with lifelong exercise training, paired with the correlation between GDF11 and peak power output, suggested that GDF11 may be a relevant myostatin‐interacting peptide to successful aging in humans, and strategies to maintain this need to be further explored.

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Section: Discussionmentioning

confidence: 99%

Lifelong exercise, but not short-term high-intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation

et al. 2017

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“…Variants of the MSTN gene are associated with muscle hypertrophy phenotypes in a range of mammalian species (Grobet et al 1997;Mosher et al 2007). Myostatin expression increases might contribute to muscle wasting, as suggested by research in animal (immobilised mice) (Carlson et al 1999) and human models, i.e.…”

Section: Discussionmentioning

confidence: 99%

Association of the K153R polymorphism in the myostatin gene and extreme longevity

Garatachea

Pinós

Cámara

et al. 2013

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The myostatin (MSTN) gene is a candidate to influence extreme longevity owing to its role in modulating muscle mass and sarcopenia and especially in inhibiting the main nutrient-sensing pathway involved in longevity, i.e. mammalian target of rapamycin. We compared allele/genotype distributions of the exonic MSTN variants K153R (rs1805086), E164K (rs35781413), I225T and P198A, in Spanish centenarians (cases, n=156; 132 women, age range 100-111 years) and younger adults (controls, n=384; 167 women, age <50 years). No subject of either group carried a mutant allele of the E164K, I225T or AGE (2013) 35:2445-2454 DOI 10.1007 Antoni L. Andreu and Alejandro Lucia share senior authorship. P198A variation. The frequency of the variant R allele was significantly higher in centenarians (7.1 %) than in controls (2.7 %) (P=0.001). The odds ratio of being a centenarian if the subject had the R allele was 3.48 (95 % confidence interval 1.67-7.28, P=0.001), compared to the control group, after adjusting for sex. The results were replicated in an Italian cohort (centenarians, n=79 (40 women), age range 100-104 years; younger controls, n=316 (155 women), age <50 years), where a higher frequency of the R allele in centenarians (7.6 %) compared to controls (3.0 %) (P=0.004) was independently confirmed. Although more research is needed, the variant allele of the MSTN K153R polymorphism could be among the genetic contributors associated with exceptional longevity.

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“…The MSTN gene encodes myostatin, a skeletal musclespecific secreted peptide that functions mainly to modulate myoblast proliferation and thus muscle mass and strength . Variants of the MSTN gene are associated with muscle hypertrophy phenotypes in a range of mammalian species, most notably cattle (Grobet et al 1997;, dogs (Mosher et al 2007) and mice . The myostatin-null mouse model also provides insights into the physiological role of this protein.…”

Section: Genotype-phenotype Association Studiesmentioning

confidence: 99%

Genes and the ageing muscle: a review on genetic association studies

Garatachea

Lucía

2011

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Western populations are living longer. Ageing decline in muscle mass and strength (i.e. sarcopenia) is becoming a growing public health problem, as it contributes to the decreased capacity for independent living. It is thus important to determine those genetic factors that interact with ageing and thus modulate functional capacity and skeletal muscle phenotypes in older people. It would be also clinically relevant to identify 'unfavourable' genotypes associated with accelerated sarcopenia. In this review, we summarized published information on the potential associations between some genetic polymorphisms and muscle phenotypes in older people. A special emphasis was placed on those candidate polymorphisms that have been more extensively studied, i.e. angiotensinconverting enzyme (ACE) gene I/D, α-actinin-3 (ACTN3) R577X, and myostatin (MSTN) K153R, among others. Although previous heritability studies have indicated that there is an important genetic contribution to individual variability in muscle phenotypes among old people, published data on specific gene variants are controversial. The ACTN3 R577X polymorphism could influence muscle function in old women, yet there is controversy with regards to which allele (R or X) might play a 'favourable' role. Though more research is needed, up-to-date MSTN genotype is possibly the strongest candidate to explain variance among muscle phenotypes in the elderly. Future studies should take into account the association between muscle phenotypes in this population and complex gene-gene and gene-environment interactions.

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A Mutation in the Myostatin Gene Increases Muscle Mass and Enhances Racing Performance in Heterozygote Dogs

Cited by 682 publications

References 28 publications

Lifelong exercise, but not short-term high-intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation

Lifelong exercise, but not short-term high-intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation

Association of the K153R polymorphism in the myostatin gene and extreme longevity

Genes and the ageing muscle: a review on genetic association studies

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