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J Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):133-42. doi: 10.1093/gerona/glu021. Epub 2014 Mar 3.

Genetic analysis of TOR complex gene variation with human longevity: a nested case-control study of American men of Japanese ancestry.

Author information

1
Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii. Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii. Basic & Clinical Genomics Laboratory, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia. brian.morris@sydney.edu.au.
2
Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii.
3
Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii. Public Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii.
4
Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii. Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.
5
Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii. Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii. Department of Human Welfare, Okinawa International University, Ginowan, Okinawa, Japan.
6
Institute for Biogenesis Research, University of Hawaii, Honolulu, Hawaii.

Abstract

The mechanistic target of rapamycin (mTOR) pathway is crucial for life span determination in model organisms. The aim of the present study was to test tagging single-nucleotide polymorphisms that captured most of the genetic variation across key TOR complex 1 (TORC1) and TOR complex 2 (TORC2) genes MTOR, RPTOR, and RICTOR and the important downstream effector gene RPS6KA1 for association with human longevity (defined as attainment of at least 95 years of age) as well as health span phenotypes. Subjects comprised a homogeneous population of American men of Japanese ancestry, well characterized for aging phenotypes and who have been followed for 48 years. The study used a nested case-control design involving 440 subjects aged 95 years and older and 374 controls. It found no association of 6 tagging single-nucleotide polymorphisms for MTOR, 61 for RPTOR, 7 for RICTOR, or 5 for RPS6KA1 with longevity. Of 40 aging-related phenotypes, no significant association with genotype was seen. Thus common genetic variation (minor allele frequency ≥10%) in MTOR, RPTOR, RICTOR, and RPS6KA1 is not associated with extreme old age or aging phenotypes in this population. Further research is needed to assess the potential genetic contribution of other mTOR pathway genes to human longevity, gene expression, upstream and downstream targets, and clinically relevant aging phenotypes.

KEYWORDS:

Genetic association analysis; Health span; Life span; Longevity; Target of rapamycin.

PMID:
24589862
PMCID:
PMC4366598
DOI:
10.1093/gerona/glu021
[Indexed for MEDLINE]
Free PMC Article

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