The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan

González-Freire, Marta; Rodríguez-Romo, Gabriel; Santiago, Catalina; Bustamante-Ara, Natalia; Yvert, Thomas; Gómez‐Gallego, Félix; Rexach, José Antonio Serra; Ruiz, Jonatan R.; Lucía, Alejandro

doi:10.1007/s11357-010-9139-7

Cited by 30 publications

(40 citation statements)

References 23 publications

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“…Similar findings were reported by Corsi et al for the isometric strength assessed in eight muscle groups in Italian Caucasians (Corsi et al 2002). We recently reported that the muscle mass and function (especially gait and balance ability, as assessed with the Tinetti scale, and capacity for performing daily life activities independently, as assessed with the Barthel score) of a very old woman (age 96 years) with the very rare MSTN 153RR genotype was in the lowest 25th sex-and agespecific percentile (Gonzalez-Freire et al 2010). In the same study, the muscle strength and mass of KR women were low to normal (~25th-50th percentile) compared to the wild-type (KK) genotype, yet their functional capacity (Barthel and Tinetti tests) was normal.…”

Section: Cross-sectional Genetic Association Studiessupporting

confidence: 88%

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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Section: Cross-sectional Genetic Association Studiessupporting

confidence: 88%

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

Garatachea

Lucía

2011

AGE

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“…In fact, the R allele has not been associated with higher muscle mass/function in old Caucasian people (aged <80 years) (see Garatachea and Lucía (2013) for a review). Carriage of one R allele does not seem to exert a major influence in the muscle phenotypes of non-agenarians (Gonzalez-Freire et al 2010) whereas, surprisingly, the only two reported Caucasian old people with the RR genotype (i.e. a Spanish woman aged 96 years and an Italian person with assumed age <80 years) seemed to have lower muscle strength than their age-matched peers (Corsi et al 2002;Gonzalez-Freire et al 2010).…”

Section: Discussionmentioning

confidence: 86%

“…Carriage of one R allele does not seem to exert a major influence in the muscle phenotypes of non-agenarians (Gonzalez-Freire et al 2010) whereas, surprisingly, the only two reported Caucasian old people with the RR genotype (i.e. a Spanish woman aged 96 years and an Italian person with assumed age <80 years) seemed to have lower muscle strength than their age-matched peers (Corsi et al 2002;Gonzalez-Freire et al 2010). Nonetheless, given the low frequency of the R allele, further research with larger population samples is needed to clearly elucidate its influence on muscle phenotypes and sarcopenia in very old people.…”

Section: Discussionmentioning

confidence: 92%

“…The resulting PCR products were genotyped by single-base extension (SBE) (Gonzalez-Freire et al 2010). The primers used for E164K, I225T, K153R and P198A were 5′-CAAACACTGTTGTAGGAGTCT-3′, 5 ′ -C T G A AT C C A A C T T A G G C A -3 ′ , 5 ′ -TTTAATACAATACAATAAAGTAGTAA-3′ and 5′-TTTTTTTTATCTCTGAAACTTGACATGAAC-3′, respectively.…”

Section: Genotype Assessmentmentioning

confidence: 99%

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

Garatachea

Pinós

Cámara

et al. 2013

AGE

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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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“…Subsequent studies showed that the R153 allele of MSTN was associated with lower muscle strength in old African American women (n = 54, 70-79 years) (Seibert et al 2001) and older Italian populations (Corsi et al 2002). González-Freire et al (2010) reported that homozygosity for the MSTN K153R polymorphism might exert a negative influence on 1RM leg press and muscle mass of women who are at the end of the human lifespan. Kostek et al (2009) found an association between the variant MSTN 153R allele and maximal isometric contraction of the elbow muscle flexors in African American young adults of both genders, yet not in Caucasians.…”

Section: Mstn Genementioning

confidence: 99%

Molecular genetic studies of gene identification for sarcopenia

et al. 2011

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Sarcopenia, which is characterized by a progressive decrease of skeletal muscle mass and function with aging, is closely related to several common diseases (such as cardiovascular and airway diseases) and functional impairment/disability. Strong genetic determination has been reported for muscle mass and muscle strength, two most commonly recognized and studied risk phenotypes for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45-90% for muscle mass. Sarcopenia has been the subject of increasing genetic research over the past decade. This review is designed to comprehensively summarize the most important and representative molecular genetic studies designed to identify genetic factors associated with sarcopenia. We have methodically reviewed whole-genome linkage studies in humans, quantitative trait loci mapping in animal models, candidate gene association studies, newly reported genome-wide association studies, DNA microarrays and microRNA studies of sarcopenia or related skeletal muscle phenotypes. The major results of each study are tabulated for easy comparison and reference. The findings of representative studies are discussed with respect to their influence on our present understanding of the genetics of sarcopenia. This is a comprehensive review of molecular genetic studies of gene identification for sarcopenia, and an overarching theme for this review is that the currently accumulating results are tentative and occasionally inconsistent and should be interpreted with caution pending further investigation. Consequently, this overview should enhance recognition of the need to validate/replicate the genetic variants underlying sarcopenia in large human cohorts and animal. We believe that further progress in understanding the genetic etiology of sarcopenia will provide valuable insights into important fundamental biological mechanisms underlying muscle physiology that will ultimately lead to improved ability to recognize individuals at risk for developing sarcopenia and our ability to treat this debilitating condition.

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The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan

Cited by 30 publications

References 23 publications

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

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

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

Molecular genetic studies of gene identification for sarcopenia

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