Viva mTOR! Caveat mTOR!

9. July 2009 by admin.

Some 288 news articles appeared in the last two days with headlines like Anti-age pill comes closer to reality and  Is Man’s Quest For Longevity Hidden in Antibiotics?  They are about the latest experimental discovery related to the  mTOR gene activation pathway and the drug Rapamycin .  In May, I posted a blog entry providing background on this subject called Longevity genes, mTOR and lifespan.  Also Aberrant mTOR signalling  is described in my treatise as one of the Additional Candidate Theories of Aging.  So, I will focus here only on the new finding except to repeat “Mammalian target of rapamycin (mTOR) is a protein encoded in humans by the FRAP1 gene.  As the name suggests, mTOR is targeted by the immunosuppressive drug rapamycin, a drug used clinically to treat graft rejection and restenosis and being tested as a treatment for autoimmune diseases.“ The generic name for rapamycin is sirolimus; it is a serine/threonine kinase inhibitor.

The study that excited the news reports is entitled Rapamycin fed late in life extends lifespan in genetically heterogeneous mice . “Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both(ref).”  “The results were pooled from three independent studies–at Jackson Laboratory, in Bar Harbor, ME; the University of Texas Health Science Center, in San Antonio; and the University of Michigan, in Ann Arbor–and coordinated by the National Institute of Aging’s Interventions Testing Program (ITP). Rapamycin is the first success story to emerge from the ITP, which systematically evaluates anti-aging drug candidates for effectiveness in mice(ref) .”

The study is important for it is the first experimental evidence of life extension via rapamycin in mammals.  It is also important for old folks like me because the treatment was started late in the lives of the mice, equivalent to the age of 60 for humans. If the results can be extrapolated to humans it would mean something like 8 years of life extension for  males, 10 years more life for males.  Long live (with) rapamycin!!

Now for the caveats.  First of all, several of the supplements in the combined anti-aging firewall in my Anti-Aging Firewalls treatise have been reported at various times to extend the lives of mice by comparable or even greater amounts.  Would the effects of taking rapamycin provide additional life extension or simply be redundant  with the life extension already provided by those substances?  The answer is unknown.  Second, rapamycin/sirolimus can be dangerous stuff to play around with.  It is a powerful immune-system suppressant and may increase the risks of infections caused by viruses and bacteria, lymphoma, skin cancer, elevated blood lipids (cholesterol and triglycerides) and decreased kidney function(ref).  Third, we are not mice kept in a controlled cage away from most infections.  We do not know what the result would have been for mice in the wild and we don’t  know what the results of sustained intake of rapamycin would be for humans.  Caveat (beware of) rapamycin!

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