title: Exceptional longevity and muscle and fitness related genotypes: a functional in vitro analysis and case-control association replication study with SNPs THRH rs7832552, IL6 rs1800795, and ACSL1 rs6552828.
abstract: There are several gene variants that are candidates to influence functional capacity in long-lived individuals. As such, their potential association with exceptional longevity (EL, i.e., reaching 100+ years) deserves analysis. Among them are rs7832552 in the thyrotropin-releasing hormone receptor (TRHR) gene, rs1800795 in the interleukin-6 (IL6) gene and rs6552828 in the coenzyme A synthetase long-chain 1 (ACSL1) gene. To gain insight into their functionality (which is yet unknown), here we determined for the first time luciferase gene reporter activity at the muscle tissue level in rs7832552 and rs6552828. We then compared allele/genotype frequencies of the 3 abovementioned variants among centenarians [n = 138, age range 100-111 years (114 women)] and healthy controls [n = 334, 20-50 years (141 women)] of the same ethnic and geographic origin (Spain). We also studied healthy centenarians [n = 79, 100-104 years (40 women)] and controls [n = 316, 27-81 years (156 women)] from Italy, and centenarians [n = 742, 100-116 years (623 women)] and healthy controls [n = 499, 23-59 years (356 women)] from Japan. The THRH rs7832552 T-allele and ACSL1 rs6552828 A-allele up-regulated luciferase activity compared to the C and G-allele, respectively (P = 0.001). Yet we found no significant association of EL with rs7832552, rs1800795 or rs6552828 in any of the 3 cohorts. Further research is needed with larger cohorts of centenarians of different origin as well as with younger old people.
authors.affiliation: Graduate School of Health and Sports Science, Juntendo University Chiba, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fuku
authors.affiliation: Biology Centre, China Institute of Sport Science Beijing, China.
authors.forename: Zi-Hong
authors.initials: ZH
authors.lastname: He
authors.affiliation: Research Institute of Hospital 12 de Octubre ("i+12") Madrid, Spain.
authors.forename: Fabian
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.affiliation: Research Institute of Hospital 12 de Octubre ("i+12") Madrid, Spain ; School of Doctorate Studies and Research, European University of Madrid Madrid, Spain.
authors.forename: Helios
authors.initials: H
authors.lastname: Pareja-Galeano
authors.affiliation: Biology Centre, China Institute of Sport Science Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Center for Supercentenarian Study, Keio University School of Medicine Tokyo, Japan.
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Center for Supercentenarian Study, Keio University School of Medicine Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition Tokyo, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Miyachi
authors.affiliation: Graduate School of Health and Sports Science, Juntendo University Chiba, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Zempo
authors.affiliation: Graduate School of Health and Sports Science, Juntendo University Chiba, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Naito
authors.affiliation: School of Doctorate Studies and Research, European University of Madrid Madrid, Spain.
authors.forename: Thomas
authors.initials: T
authors.lastname: Yvert
authors.affiliation: School of Doctorate Studies and Research, European University of Madrid Madrid, Spain.
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Verde
authors.affiliation: Department of Health Sciences, University of Pavia Pavia, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Venturini
authors.affiliation: School of Doctorate Studies and Research, European University of Madrid Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fiuza-Luces
authors.affiliation: Research Institute of Hospital 12 de Octubre ("i+12") Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Santos-Lozano
authors.affiliation: INEF, Universidad Politécnica Madrid, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rodriguez-Romo
authors.affiliation: Department of Health Sciences, University of Pavia Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ricevuti
authors.affiliation: Center for Supercentenarian Study, Keio University School of Medicine Tokyo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
authors.affiliation: Department of Health Sciences, University of Pavia Pavia, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.affiliation: School of Doctorate Studies and Research, European University of Madrid Madrid, Spain ; Department of Physiotherapy and Nursing, Faculty of Health and Sport Science, University of Zaragoza Huesca, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Garatachea
authors.affiliation: Research Institute of Hospital 12 de Octubre ("i+12") Madrid, Spain ; School of Doctorate Studies and Research, European University of Madrid Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
keywords: centenarians; gene association study; luciferase reporter; muscle and sarcopenia; polymorphisms