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Advancing age is associated with gene expression changes resembling mTOR inhibition: evidence from two human

Lorna W Harries1, Alexander D Fellows, Luke C Pilling

  • 1Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX2 5DW, UK.

Mechanisms of Ageing and Development
|July 21, 2012
PubMed

Insights

Mammalian target of rapamycin (mTOR) signaling pathway gene expression changes with age in humans. These findings in aging populations suggest potential links to lifespan and future therapeutic interventions.

Area of Science:

  • Genetics and Molecular Biology
  • Aging Research
  • Human Physiology

Background:

  • Inhibiting the mechanistic target of rapamycin (mTOR) pathway increases lifespan in model organisms.
  • The specific role of mTOR signaling in human aging remains largely undetermined.
  • Understanding mTOR's influence on human aging is crucial for developing interventions.

Purpose of the Study:

  • To investigate the association between mTOR-related gene expression and chronological aging in human populations.
  • To identify specific mTOR pathway genes that correlate with age across independent cohorts.
  • To compare human aging-related gene expression patterns with those observed in mTOR inhibition studies.

Main Methods:

  • Analyzed mTOR-related transcript expression in two independent human cohorts: the InCHIANTI study and the San Antonio Family Heart Study (SAFHS).
  • Utilized statistical analysis with correction for multiple testing to identify age-associated genes.
  • Validated age-related gene associations across both study cohorts.

Main Results:

  • A significant number of mTOR-related genes (27/56 in InCHIANTI, 19/44 in SAFHS) showed association with age.
  • Eight genes demonstrated robust age association in both cohorts, implicating pathways in insulin signaling, apoptosis, angiogenesis, and stress response.
  • Genes related to ribosomal biogenesis and inflammatory mediators showed inverse and positive correlations with age, respectively.

Conclusions:

  • The expression of mTOR-related transcripts is significantly associated with advancing age in humans.
  • Observed gene expression changes in aging humans mirror those seen in animal models with inhibited mTOR activity and extended lifespan.
  • Further research is warranted to determine if these age-related mTOR pathway changes predict human longevity and if mTOR inhibition is beneficial in older adults.

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