Advancing age is associated with gene expression changes resembling mTOR inhibition: evidence from two human populations
Language: 
English
Short Title: 
Advancing age is associated with gene expression changes resembling mTOR inhibition
Abstract: 

Interventions which inhibit TOR activity (including rapamycin and caloric restriction) lead to downstream gene expression changes and increased lifespan in laboratory models. However, the role of mTOR signaling in human aging is unclear. We tested the expression of mTOR-related transcripts in two independent study cohorts; the InCHIANTI population study of aging and the San Antonio Family Heart Study (SAFHS). Expression of 27/56 (InCHIANTI) and 19/44 (SAFHS) genes were associated with age after correction for multiple testing. 8 genes were robustly associated with age in both cohorts. Genes involved in insulin signaling (PTEN, PI3K, PDK1), ribosomal biogenesis (S6K), lipid metabolism (SREBF1), cellular apoptosis (SGK1), angiogenesis (VEGFB), insulin production and sensitivity (FOXO), cellular stress response (HIF1A) and cytoskeletal remodeling (PKC) were inversely correlated with age, whereas genes relating to inhibition of ribosomal components (4EBP1) and inflammatory mediators (STAT3) were positively associated with age in one or both datasets. We conclude that the expression of mTOR-related transcripts is associated with advancing age in humans. Changes seen are broadly similar to mTOR inhibition interventions associated with increased lifespan in animals. Work is needed to establish whether these changes are predictive of human longevity and whether further mTOR inhibition would be beneficial in older people.

Author(s): 
Harries, Lorna W.
Fellows, Alexander D.
Pilling, Luke C.
Hernandez, Dena
Singleton, Andrew
Bandinelli, Stefania
Guralnik, Jack
Powell, Jonathan
Ferrucci, Luigi
Melzer, David
Item Type: 
Journal Article
Publication Title: 
Mechanisms of Ageing and Development
Journal Abbreviation: 
Mech. Ageing Dev.
Publication Date: 
2012-08
Publication Year: 
2012
Pages: 
556-562
Volume: 
133
Issue: 
8
ISSN: 
1872-6216
DOI: 
10.1016/j.mad.2012.07.003
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22813852 PMCID: PMC3998676

Turabian/Chicago Citation

Lorna W. Harries, Alexander D. Fellows, Luke C. Pilling, Dena Hernandez, Andrew Singleton, Stefania Bandinelli, Jack Guralnik, Jonathan Powell, Luigi Ferrucci and David Melzer. 2012-08. "Advancing age is associated with gene expression changes resembling mTOR inhibition: evidence from two human populations." Mechanisms of Ageing and Development 133: 8: 556-562. 10.1016/j.mad.2012.07.003.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.mad.2012.07.003 | issn = 1872-6216 | volume = 133 | pages = 556-562 | last = Harries | first = Lorna W. | coauthors = Fellows, Alexander D., Pilling, Luke C., Hernandez, Dena, Singleton, Andrew, Bandinelli, Stefania, Guralnik, Jack, Powell, Jonathan, Ferrucci, Luigi, Melzer, David | title = Advancing age is associated with gene expression changes resembling mTOR inhibition: evidence from two human populations | journal = Mechanisms of Ageing and Development | date = 2012-08 | pmid = | pmc = }} </ref>