Association of the K153R polymorphism in the myostatin gene and extreme longevity.
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 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.
Facultad de Ciencias de la Salud y del Deporte, Universidad de Zaragoza, Huesca, Spain.
Nuria
N
Garatachea
Tomàs
T
Pinós
Yolanda
Y
Cámara
Gabriel
G
Rodríguez-Romo
Enzo
E
Emanuele
Giovanni
G
Ricevuti
Letizia
L
Venturini
Alejandro
A
Santos-Lozano
Catalina
C
Santiago-Dorrego
Carmen
C
Fiuza-Luces
Thomas
T
Yvert
Antoni L
AL
Andreu
Alejandro
A
Lucia
D000369:Aged, 80 and over; D000483:Alleles; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D055948:Sarcopenia / Q000235:genetics / Q000378:metabolism
C525911:MSTN protein, human; D055435:Myostatin; D004247:DNA