Immune drug boosts lifespan

A drug used to prevent the rejection of transplanted organs and as an experimental cancer treatment in humans can significantly increase lifespan when given to adult mice, researchers have found. Mice that were administered the immunosuppressant rapamycin lived an average of 9-14% longer than mice that were not fed the drug, according to a paper published online in __Nature__ today (July 8th). "Four times a mouse" by Jacquesde GheynImage: Wikimedia"This is pretty remarkable,"

By | July 8, 2009

A drug used to prevent the rejection of transplanted organs and as an experimental cancer treatment in humans can significantly increase lifespan when given to adult mice, researchers have found. Mice that were administered the immunosuppressant rapamycin lived an average of 9-14% longer than mice that were not fed the drug, according to a paper published online in __Nature__ today (July 8th).
"Four times a mouse" by Jacques
de Gheyn

Image: Wikimedia
"This is pretty remarkable," linkurl:Panjak Kapahi,; a geneticist at the Buck Institute for Age Research in California told __The Scientist__. "There might be more to gain in understanding the downstream effects, but this is already a wonderful start." Kapahi, who was not involved with the study, added that, though preliminary, the finding opens the door for further research into the drug's use for an anti-aging intervention in humans. "It should be applicable to humans, I think." linkurl:David Harrison,; a gerontologist at The Jackson Laboratory in Bar Harbor Maine and lead author on the paper, told __The Scientist__ that 9%, though seemingly a modest life span increase, is significant when compared to the effect of eradicating some of the most common age-related diseases in humans. "If you prevented all deaths from cancer and atherosclerosis," Harrison said, "it would be a little less than that." Rapamycin works by inhibiting the target of rapamycin (TOR) signaling pathway, which plays a role in the translating mRNA into proteins and inhibits processes that degrade cellular waste. The drug has been found to extend the life spans of yeast, fruit flies, and nematodes. "This is really the first demonstration that inhibiting TOR also increases lifespan in mammals," said linkurl:Matt Kaeberlein,; a pathologist at the University of Washington in Seattle who was not involved with the study. Kapahi, who linkurl:discovered; in 2004 that the TOR pathway played a role in extending the life spans of fruit flies, said that Harrison's study is both a "great victory for the invertebrate models of aging," and a fruitful way forward to investigate a potential anti-aging treatment in humans. "You would put your money on a pathway that you know has worked in four different organisms," he said. "This is as good as it gets." As rapamycin has previously been shown to increase the life spans of invertebrate model organisms, its effect in mice is not entirely surprising, according to Kaeberlein, who wrote a commentary that accompanies the __Nature__ paper. More surprising is the fact that the longer-lived mice in the study were not given rapamycin until they were 600 days old. "That is very surprising to myself and to a lot of people," Kaeberlein told __The Scientist__. "And it's a very important result." A 600-day-old mouse is roughly equivalent to a human that is 60 years of age, and other successful anti-aging interventions have not proved effective so late in an organism's life. Kaeberlein said that rapamycin's effectiveness in middle aged mice represents an interesting therapeutic opportunity in humans, because "almost everything that has been found to significantly increase lifespan in model organisms leads to some sort of fitness costs" -- usually by stunting growth or reducing reproductive capacity. A rapamycin-based anti-aging pill administered later in life might circumvent these problems. Harrison agreed. "It's certainly possible that there may be optimal times to start things when you're old that might be deleterious when you're young," he said. But he joined Kaeberlein and Kapahi in cautioning that the findings should not be interpreted as an invitation for age-conscious humans to ingest the drug. "It's not time to start popping rapamycin for anti-aging," Harrison said, adding that taking rapamycin likely carries significant risks common to other immune suppressants or immunocompromising diseases. Several questions surrounding the results and rapamycin's impact on the TOR pathway and aging remain to be answered. "What's happening in these animals that are given rapamycin and are living a long time?" asked Kaeberlein. "That's going to be important for the next set of experiments to look at." Harrison said that he and other researchers collaborating in the National Institute on Aging's linkurl:Interventions Testing Program; are examining the drug's cellular effects and testing a suit of other compounds suspected to increase the longevity of mammals. The effect of rapamycin and the indication that the TOR pathway is important in mammalian aging is a major step towards developing a drug that might prolong human life, he said. "I think this makes us a lot closer than we were before," he said. "Who knows what's going to work, but we have a point here that's ever so much more specific and interesting than we had to start with."
**__Related stories:__***linkurl:Proteins link diet to longevity;
[24th June 2009]*linkurl:Fat chance for long life;
[6th November 2008]*linkurl:Want longevity? Call a friend;
[27th May 2008]


Avatar of: Hans Weber

Hans Weber

Posts: 5

July 8, 2009

In the chapter "Death" in his new book, "Life Ascending", Nick Lane mentions TOR and the potential benefits of rapamycin to delay aging. Since aging is associated with cancer, cardiovascular, and other degenerative diseases, its delay would keep such diseases at bay, thus assuring a longer healthier life. Lane considers an anti-aging pill a real possibility.
Avatar of: anonymous poster

anonymous poster

Posts: 11

July 8, 2009

J Biol Chem. 2006 Sep 15;281(37):27643-52. Epub 2006 Jul 17.Related Articles, Links \nThe mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity.\n\nSchieke SM, Phillips D, McCoy JP Jr, Aponte AM, Shen RF, Balaban RS, Finkel T.\n\nCardiology Branch, Laboratory of Cardiac Energetics, Flow Cytometry Core Facility, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.\n\nMetabolic rate and the subsequent production of reactive oxygen species are thought to contribute to the rate of aging in a wide range of species. The target of rapamycin (TOR) is a well conserved serine/threonine kinase that regulates cell growth in response to nutrient status. Here we demonstrate that in mammalian cells the mammalian TOR (mTOR) pathway plays a significant role in determining both resting oxygen consumption and oxidative capacity. In particular, we demonstrate that the level of complex formation between mTOR and one of its known protein partners, raptor, correlated with overall mitochondrial activity. Disruption of this complex following treatment with the mTOR pharmacological inhibitor rapamycin lowered mitochondrial membrane potential, oxygen consumption, and ATP synthetic capacity. Subcellular fractionation revealed that mTOR as well as mTOR-raptor complexes can be purified in the mitochondrial fraction. Using two-dimensional difference gel electrophoresis, we further demonstrated that inhibiting mTOR with rapamycin resulted in a dramatic alteration in the mitochondrial phosphoproteome. RNA interference-mediated knockdown of TSC2, p70 S6 kinase (S6K1), raptor, or rictor demonstrates that mTOR regulates mitochondrial activity independently of its previously identified cellular targets. Finally we demonstrate that mTOR activity may play an important role in determining the relative balance between mitochondrial and non-mitochondrial sources of ATP generation. These results may provide insight into recent observations linking the TOR pathway to life span regulation of lower organisms.\n\nSee more work from this group.\n\n
Avatar of: tian xia

tian xia

Posts: 34

July 8, 2009

Rapamycin inhibit mTOR --- promote autophagy--- get rid of old used organelles such as mitochondria-- produce more ATP cytosolically---cells become leaner and more efficient ----similar to effect of calerie restriction overall by mobilizing what you have.
Avatar of: Keith Loritz

Keith Loritz

Posts: 16

July 9, 2009

Are these mice living longer because they now have less chance of dying from cancer? \n\nor\n\nDid the incidence of death from cancer in these mice go down when the drug was administered?
Avatar of: Eric Siegel

Eric Siegel

Posts: 1

July 21, 2009

In the Nature paper by Harrison et al, take a close look at the left panel of Figure 1, and ask yourself, how is it that male mice in the rapamycin group start showing a survival benefit 200 days *before* their first exposure to rapamycin? Now take a close look at the top panels in Figure 2, and ask yourself, how is it that this peculiarly anticipative rapamycin benefit is blatantly manifest in two institutions but absent in the third?

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