Inhibition of the mTOR pathway extends life span
A new study published in Science Translational Medicine confirms that blocking the mTOR pathway boosts elderly immune systems by up to 20 percent. (1) Before this study, animal experimentation showed that this approach extends life span in mice up to 14 percent, even when treatment is initiated late in life. (2)
Because it would take decades to test the effect of mTOR molecules on life span in humans, the researchers at Novartis Institutes for BioMedical Research et al used a proxy called Roo1. (2) The goal was to measure the decline in immune function in seniors’ (age 65 and older) during aging, as assessed by their response to a flu vaccine. (3). They found that Roo1 R001 boosted immune systems response to a flu vaccine by 20 percent. (4).The researchers also found that R001 reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. (1)
However, given potential negative side effects, the immune-enhancing effects of mTOR inhibitors need to be verified with additional studies because :
“…the toxicity of RAD001 at doses used in oncology or organ transplantation results in adverse effects such as stomatitis, diarrhea, nausea, cytopenias, hyperlipidemia, and hyperglycemia.”
Up to now, the inhibition of the mTOR (Mammalian target of rapamycin) pathway has shown to extend life span in all animal species studied to date. We now have evidence that this Roo1 molecule can also extend the immune system’s lifespan and slow down immunosenescence in the elderly. Given potential side effects though, further human research is warranted. The OL Institute will keep the viewer updated.
(1). Joan B. Mannick et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med 24 December 2014: Vol. 6, Issue 268.
(2). In the mice studies, there were other improvements from a variety of aging-related conditions in old mice, including, but not limited to tendon stiffening, cardiac dysfunction, cognitive decline, and decreased mobility. These comorbidities regressed independently of a specific disease process.
(3). This drug’s full name is everolimus (or RAD001), a version the well known anti-aging drug called rapamycin (sirolimus). Rapamycin and RAD001 belong to a class of drugs known as “mTOR inhibitors.” mTOR means “Mammalian target of rapamycin”.
(4). Immune-system aging is a major cause of disease and death, making older people more susceptible to infections and cancer. They also tend to have a weaker response to vaccines.
The Study’s complete Citation:
J. B. Mannick, G. Del Giudice, M. Lattanzi, N. M. Valiante, J. Praestgaard, B. Huang, M. A. Lonetto, H. T. Maecker, J. Kovarik, S. Carson, D. J. Glass, L. B. Klickstein, mTOR inhibition improves immune function in the elderly. Sci. Transl. Med. 6, 268ra179 (2014).
The authors: Joan B. Mannick (1), Giuseppe Del Giudice (2), Maria Lattanzi (2), Nicholas M. Valiante (3), Jens Praestgaard (4), Baisong Huang1, Michael A. Lonetto1, Holden T. Maecker (5), John Kovarik (6), Simon Carson (7), David J. Glass1 and Lloyd B. Klickstein
1 Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
2 Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
3 Novartis Vaccines and Diagnostics, Cambridge, MA 02139, USA.
4 Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
5 Stanford University School of Medicine, Stanford, CA 94305–5124, USA.
6 Novartis Pharmaceuticals Corporation, CH-4002 Basel, Switzerland.
7 Southern Clinical Trials, Christchurch 8024, New Zealand.
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