New Results Suggest That Rapamycin Doesn't Slow Aging

Contrary to earlier research wherein scientists concluded that rapamycin extends life by slowing aging, here another group proposes that the extended life observed in laboratory animals results from cancer suppression, and aging isn't greatly impacted. Drugs that can slow aging are in any case a sideshow, a line of research that will require decades and billions but is incapable of producing ways to rejuvenate the old. Only SENS and similar repair-based research programs have the potential to result in therapies that will extend the healthy lives of the elderly and restore their lost vigor and youth. So if the scientific community is going to spend the few decades between now and my old age working on new medicine, I'd rather they ditched the old-style drug discovery pipeline in favor of a research strategy that is actually likely to benefit me. As to the debate on rapamycin:

Rapamycin is used in recipients of organ transplants, as it keeps the immune system in check and can consequently prevent rejection of the foreign tissue. In 2009, US scientists discovered another effect: Mice treated with rapamycin lived longer than their untreated counterparts. "Rapamycin was the first drug shown to extend maximal lifespan in a mammalian species. This study has created quite a stir. We wanted to address if rapamycin slows down aging in mice or, alternatively, if it has an isolated effect on lifespan - without broadly modulating aging."

"Our results indicate that rapamycin extends lifespan, but it has only limited effects on the aging process itself. Most aging traits were not affected by rapamycin treatment. Although we did observe positive effects on some aging traits, such as memory impairments and reduced red blood cell counts, our studies showed that similar drug effects are also seen in young mice, indicating that rapamycin did not influence these measures by slowing aging, but rather via other, aging-independent, mechanisms."

The researchers believe that such aging-independent drug effects also underlie rapamycin's effect on lifespan. "We assume that the lifespan of mice is extended because rapamycin inhibits tumor formation. This is a well-known rapamycin effect, which we were able to confirm. Cancer is the leading cause of death in the relevant mouse strains. Rapamycin, therefore, seems to have isolated effects on specific life-limiting pathology, but lacks broad effects on aging in mice."

"Generally speaking, our studies show that a number of different parameters have to be considered when assessing the efficacy of possible anti-aging interventions. The interpretation of the data depends heavily on the overall picture of findings. Lifespan measures alone are not a reliable indicator of anti-aging effects. This makes the search for anti-aging medicines tedious, but it is also very promising, because such substances could open up new possibilities for medicine. However, this is still some way off."



Rapamycin did extend mice life expectancy in the study, however. So, even if it did not slow major processes of aging, it did extend their lifespans. And if it did so through an anti-cancer effect as the authors suggest, so what? Isn't cancer one of the seven types of aging damage postulated by Aubrey de Grey and SENS?

Obviously it won't have such an appreciable impact on human longevity and its no replacement for SENS. But at the same time, hundreds of millions of dollars are spent each year on worthless ostensibly anti-aging snake-oil pills.

Posted by: Therapsid at July 26th, 2013 11:52 AM

There have been numerous reports demonstrating that rapamycin not only extends survival but also slows aging in mice (see "Rapamycin Slows Aging in Mice" for one recent example: Furthermore, if you download and read the extensive supplemental data you'll see that the authors of this paper do see a robust rescue of a few phenotypes in their mice - most appreciable is a rescue of age-related cardiac dysfunction. The choice to interpret their largely non-significant results as demonstrating that rapamycin doesn't affect aging is not only misguided and illogical (they test a single dosage in a single strain, this is hardly sufficient to determine that a drug doesn't do something) but also disagrees with dozens of reports from well respected laboratories that show otherwise.

Posted by: Simon Johnson at August 11th, 2013 8:55 PM

Aging (Albany NY). 2013 Aug 10. [Epub ahead of print]
Rapamycin extends life- and health span because it slows aging.
Blagosklonny MV.
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, L3-312, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
Making headlines, a thought-provocative paper by Neff, Ehninger and coworkers claims that rapamycin extends life span but has limited effects on aging. How is that possibly possible? And what is aging if not an increase of the probability of death with age. I discuss that the JCI paper actually shows that rapamycin slows aging and also extends lifespan regardless of its direct anti-cancer activities. Aging is, in part, MTOR-driven: a purposeless continuation of developmental growth. Rapamycin affects the same processes in young and old animals: young animals' traits and phenotypes, which continuations become hyperfunctional, harmful and lethal later in life.
PMID: 23934728 [PubMed - as supplied by publisher] Free full text

Posted by: Mikhail Blagosklonny at August 18th, 2013 11:44 AM

I find your article to be skewed by your opinion. You seem to be biased against drugs that slow aging to the point that you call them a "sideshow" that will "cost billions of dollars", yet do nothing to rejuvenate cells.
I think this attitude has caused you to throw the baby out with the bathwater.
First, I'm more than happy to have cell aging slowed. Just because it can't reverse my age, doesn't mean it can't extend the years I have left that I value, that you apparently don't value as much unless you are younger.

Secondly, and more importantly, age-slowing drugs can be a step on the path to age-reversing drugs. Why not pursue both avenues?

You seem to express the attitude that unless drugs reverse aging, they are a time-wasting, expensive "sideshow" that takes away from real research, i.e. the research you value. I think that is short-sighted, and actually counter-productive, as I am sure biologists will discover considerable overlap between them.

Posted by: MaskedMarvyl at September 3rd, 2013 5:40 PM
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