The candidate genes' expression level was again tested for association with familial longevity, but now adjusted for blood cell subtypes. The references section contains several scientific articles related to the study's topic. The authors thank all participants of the Leiden Longevity Study. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2011) under grant agreement no. 259679. This study was supported by a grant from the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology, the Netherlands Consortium for Healthy Ageing (Grant 050-060-810), all in the framework of the Netherlands Genomics Initiative, the Netherlands Organization for Scientific Research (NWO), and by Unilever Colworth. David A. Gunn is employed by Unilever PLC and involved in the design, data collection and analysis as well as the decision to publish.And glucocorticoid-induced protein kinase (SGK). Biochem. J., Goeman JJ, Oosting J () Globaltest R package, version. Ref Type: Computer Program. Goeman JJ, van de Geer SA, de Kort F, van Houwelingen JC () A global test for groups of genes: testing association with a clinical outcome. Bioinformatics, Goeman JJ, Oosting J, Cleton-Jansen AM, Anninga JK, van Houwelingen HC () Testing association of a pathway with survival using gene expression data. Bioinformatics, Barzilai N, Gabriely I, Gabriely M, Iankowitz N, Sorkin JD (2001) Offspring of centenarians have a favorable lipid profile. J. Am. Geriatr. Soc. 49, 7679. Brown J, Wang H, Suttles J, Graves DT, Martin M (2011) Mammalian target of rapamycin complex 2 (mTORC2) negatively regulates toll-like receptor 4-mediated Sarbassov DD, Guertin DA, Ali SM, Sabatini DM () Phosphorylation and regulation of Akt/PKB by the rictor-OR complex. Science, Schoenmaker M, de Craen AJ, de Meijer PH, Beekman M, Blauw GJ, Slagboom PE, Westendorp RG () Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study. Eur. J. Hum. Genet., Sengupta S, Peterson TR, Sabatini DM () Regulation of the OR complex pathway by nutrients, growth factors and stress. Mol. Cell , Soukas AA, Kane EA, Carr CE, Melo JA, Ruvkun G () Rictor/TORC regulates fat metabolism, feeding, growth, and lifespan in Caenorhabditis elegans. Genes Dev., Spindler SR () Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction. Mech. Ageing Dev., Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy BK () The TOR pathway comes of age. Biochim. Biophys. Acta, Stat orp () Stata Statistical Software: Release College Station, TX: Stat orp LP. Strimpakos A, Saif MW, Syrigos KN () Pancreatic cancer: from molecular pathogenesis to targeted therapy. Cancer Metastasis Rev., Thedieck K, Polak P, Kim ML, Molle KD, Cohen A, Jeno P, Arrieumerlou C, Hall MN () PRAS and PRR-like protein are new OR interactors that regulate apoptosis. PL One , e Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F () Genetics: influence of TOR kinase on lifespan in C. elegans. Nature , Westendorp RG, van Heemst D, Rozing MP, Frolich M, Mooijaart SP, Blauw GJ, Beekman M, Heijmans BT, de Craen AJ, Slagboom PE () Nonagenarian siblings and their offspring display lower risk of mortality and morbidity than sporadic nonagenarians: The Leiden Longevity Study. J. Am. Geriatr. Soc., Wijsman CA, Rozing MP, Streefland TC, le Cessie S, Mooijaart SP, Slagboom PE, Westendorp RG, Pijl H, van Heemst D (2011) Familial longevity is marked by enhanced insulin sensitivity. Aging Cell 10, 114121. Enhanced insulin sensitivity. Aging Cell 10, 114121. Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P (2008) Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr. Opin. Pharmacol. 8, 393412.
Supporting Information
Additional Supporting Information may be found in the online version of this article on the publisher's website.
Table S1 Analyzed samples: genetic variation.
S2 Measured SNPs in the mTOR pathway.
S3 Results of gene set analysis of the mTOR pathway gene SNP Table S4 Linear regression results of gene expression of offspring compared with controls, including adjustments for T-cell differentiation markers.
Table S5 Descriptives of prevalence of disease and metabolic syndrome-related parameters in offspring and controls (n = 658).
T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F (2003) Genetics: influence of TOR kinase on lifespan