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mTOR inhibition improves immune function in the elderly

Joan B Mannick1, Giuseppe Del Giudice2, Maria Lattanzi2

  • 1Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA. joan.mannick@novartis.com.

Science Translational Medicine
|December 26, 2014
PubMed

Insights

Inhibition of the mammalian target of rapamycin (mTOR) pathway with RAD001 improved immune response in elderly volunteers. This suggests potential benefits for age-related immune decline and function.

Area of Science:

  • Gerontology and Immunology
  • Molecular Biology and Aging Research

Background:

  • The mammalian target of rapamycin (mTOR) pathway is crucial for cell growth and metabolism, and its inhibition extends lifespan in model organisms.
  • Aging is associated with a decline in immune function, known as immunosenescence, increasing susceptibility to infections and reducing vaccine efficacy.
  • The effects of mTOR inhibition on human aging and immunosenescence remain largely unexplored.

Purpose of the Study:

  • To investigate whether the mTOR inhibitor RAD001 can ameliorate immunosenescence in elderly humans.
  • To assess the impact of RAD001 on immune response to influenza vaccination in older adults.

Main Methods:

  • A study involving elderly volunteers was conducted to evaluate the effects of RAD001.
  • Immunosenescence was assessed by measuring the response to influenza vaccination.
  • Changes in T lymphocyte populations, specifically CD4 and CD8 T cells expressing the programmed death-1 (PD-1) receptor, were analyzed.

Main Results:

  • RAD001 treatment enhanced the immune response to the influenza vaccine by approximately 20% in elderly participants.
  • The drug was found to be relatively well tolerated at the tested doses.
  • RAD001 significantly reduced the percentage of CD4 and CD8 T lymphocytes expressing the PD-1 receptor, a marker of immune aging.

Conclusions:

  • mTOR inhibition with RAD001 shows promise in improving immune function in the elderly.
  • These findings suggest that targeting the mTOR pathway could be a therapeutic strategy to combat age-related immune decline.
  • Further research is warranted to explore the broader implications of mTOR inhibition on human aging and healthspan.

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