Gene expression analysis of mTOR pathway: association with human longevity

Aging Cell

Willemijn M. Passtoors³  Marian Beekman³  Joris Deelen³  Ruud van der Breggen³  Andrea B. Maier¹  Bruno Guigas²  Evelyna Derhovanessian⁵  Diana van Heemst¹  Anton J. M. de Craen¹  David A. Gunn⁴  Graham Pawelec⁵ 

[1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands;Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands;Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands;Unilever Discover, Colworth, Sharnbrook, Bedfordshire, UK;Center for Medical Research, University of Tübingen, Tübingen, Germany

关键词: aging;    longevity;    mTOR;    human;    gene expression;   

DOI  :  10.1111/acel.12015

来源: Wiley

【 摘 要 】

Summary

mTOR signalling is implicated in the development of disease and in lifespan extension in model organisms. This pathway has been associated with human diseases such as diabetes and cancer, but has not been investigated for its impact on longevity per se. Here, we investigated whether transcriptional variation within the mTOR pathway is associated with human longevity using whole-blood samples from the Leiden Longevity Study. This is a unique cohort of Dutch families with extended survival across generations, decreased morbidity and beneficial metabolic profiles in middle-age. By comparing mRNA levels of nonagenarians and middle-aged controls, the mTOR signalling gene set was found to associate with old age (P = 4.6 × 10⁻⁷). Single gene analysis showed that seven of 40 mTOR pathway genes had a significant differential expression of at least 5%. Of these, the RPTOR (Raptor) gene was found to be differentially expressed also when the offspring of nonagenarians was compared with their spouses, indicating association with familial longevity in middle-age. This association was not explained by variation between the groups in the prevalence of type 2 diabetes and cancer or glucose levels. Thus, the mTOR pathway not only plays a role in the regulation of disease and aging in animal models, but also in human health and longevity.

【 授权许可】

Unknown   
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland