;

:

–

Kenyon CJ: The genetics of ageing. Nature

;

:

–

Anselmi CV, Malovini A, Roncarati R et al: Association of the FOXO

A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res

;

:

–

Flachsbart F, Caliebe A,Kleindorp R et al: Association o

OXO

Avariation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA

;

:

–

Li Y, Wang WJ, Cao H et al: Genetic association of FOXO

A and FOXO

A with longevity trait in Han Chinese populations. Hum Mol Genet

;

:

–

Pawlikowska L, Hu D, Huntsman S et al: Association of common genetic variation in the insulin/IGF

signaling pathway with human longevity. Aging Cell

;

:

–

Soerensen M, Dato S, Christensen K et al: Replication of an association of variation in the FOXO

A gene with human longevity using both case-control and longitudinal data. Aging Cell

;

:

–

Willcox BJ, Donlon TA, He Q et al: FOXO

A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA

;

:

–

Nybo H, Gaist D, Jeune B et al: The Danish

cohort: a genetic-epidemiological nationwide survey. J Aging Health

;

:

–

Soerensen M, Dato S, Tan Q et al: Human longevity and variation in GH/IGF-

/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: Cross sectional and longitudinal studies. Exp Gerontol

;

:

–

Pedersen CB, Gotzsche H, Moller JO, Mortensen PB: The Danish Civil Registration System. A cohort of eight million persons. Dan Med Bull

;

:

–

Skytthe A, Kyvik K, Holm NV, Vaupel JW, Christensen K: The Danish Twin Registry:

birth cohorts of twins. Twin Res

;

:

–

Nebel A, Croucher PJ, Stiegeler R, Nikolaus S, Krawczak M, Schreiber S: No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans. Proc Natl Acad Sci USA

;

:

–

In conclusion, despite a substantial power, we did not confirm AKT1 as a longevity-associated gene in populations of Danish and German nonagenarians and centenarians. This finding does not necessarily rule out a potential relevance of AKT1 in longevity. First, population genetic differences may explain the lack of replication, although this explanation is not very likely, because all analyzed populations were of European ancestry. Second, because our coverage of allelic variation in AKT1 is probably not complete, other variations that are not tagged by the included SNPs may be associated with survival differences. However, all in all, our results do suggest that AKT1 is not a universally acting longevity gene.

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

This study was financially supported by the INTERREG 4A programme Syddanmark–Schleswig–K.E.R.N (with EU funds from the European Regional Development Fund), the National Institute on Aging (P01 AG08761), the Max–Planck Institute for Demographic Research (Rostock, Germany), the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence ‘Inflammation at Interfaces’, and the RESOLVE project (FP7-HEALTH-F4-2008-202047).

Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel JW: The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Hum Genet 1996; 97: 319–323.

Copyright of European Journal of Human Genetics is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.