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BRIEF Rapamycin exposure in middle age dramatically extends LS

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... in mice. Our old - once upon a time - friend Matt Kaeberlein is doing some fine work:

 

Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

 

"Now, Bitto et al. show that treating mice with rapamycin for a short period during middle age increases the life expectancy of the mice by up to 60%. In the experiments, mice were given two different doses of rapamycin for only three months starting at 20 months old (equivalent to about 60-65 years old in humans). After receiving the lower dose, both male and female mice lived about 50% longer than untreated mice, and showed improvements in their muscle strength and motor coordination. When given the higher dose, male mice showed an even greater increase in life expectancy, but the female mice did not. These female mice had an increased risk of developing rare and aggressive forms of blood cancer, but were protected from other types of cancer."

 

Before you orgasm from excitement at the "brief" and "60%", please remember, you are not a mouse.

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Thanks Tom,
 

Before you orgasm from excitement at the "brief" and "60%", please remember, you are not a mouse.

 

There are (at least) two other reasons to avoid getting too excited about this result. First, it is important to recognize that the "60%" figure refers to remaining life extension (RLE). Roughly, a 65 year old human can expect to live about 20 more years. So if scaled directly to (male) humans, this result would imply an additional 10-12 more years. Still huge (and unrealistic for humans), but not an extra ~50 years that a naive reading of 60% life extension would suggest.

 

Plus it is important to point out that among other side effects, rapamycin suppresses the immune system. That is why it is prescribed to solid organ transplant recipients, to prevent them from rejecting their new organ.

 

This immunocompromised state might not be so bad for mice living in (relatively) germs free lab conditions. But humans (or mice!) living in the wild could very well have their life shortened by rapamycin's effects on the immune system via suppression of the mTOR complex.

 

--Dean

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[...]

Plus it is important to point out that among other side effects, rapamycin suppresses the immune system. That is why it is prescribed to solid organ transplant recipients, to prevent them from rejecting their new organ.

 

This immunocompromised state might not be so bad for mice living in (relatively) germs free lab conditions. But humans (or mice!) living in the wild could very well have their life shortened by rapamycin's effects on the immune system via suppression of the mTOR complex.

 

--Dean

 

 

Yes and no - it all depends on dosage, as I've repeatedly stressed. We know that a compromised immune system makes you vulnerable not only to opportunistic infections, but to all other deleterious effects of such a condition, including greater susceptibility to cancer, as seen in transplant patients who are on rapa. Yet, it is also true, that there are studies showing - at least in murines - that at a lower dosage rapa actually enhances the immune system (perhaps through hormesis?) and the result is fewer cancers in those animals. There were also some studies in elderly humans that seemed to not show deleterious immune (or other) effect and rapa was well tolerated. The trick of course is in finding a dosage that gives you the good effects of rapa without the bad, or a reasonable compromise - if that is even possible. And again - humans and rats/mice really are very different and we can't just extrapolate these studies. Not that I would reject 10-12 years beyond my max LS if possible without bad side effects :)

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TomB wrote:

Our old - once upon a time - friend Matt Kaeberlein is doing some fine work:

 
Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

 

and in response to my concern about rapamycin's well-known side effects including immune system suppression and cancer promotion, Tom wrote:

Yes and no - it all depends on dosage, as I've repeatedly stressed. 

 

Granted. But even our friend Matt Kaeberlein, who believes rapamycin has more potential as an anti-aging compound than SIRT1-promoters like resveratrol or NAD-boosters like pterostilbene or NR, and who is studying rapamycin's effects in mice and dogs, says he isn't prepared to take it just yet:

 

Kaeberlein takes nothing but says he’s “getting more and more tempted to take rapamycin in a low dose.”

 

So I'll wait until a smart guy like Matt (or Michael) starts to take it before considering it for myself.

 

BTW, that article is a good one profiling Elysium Health's Basis pill (a combination of  pterostilbene or NR) and the people behind it. It illustrates the fine line many of these guys (Guarente, Sinclair) walk between being scientists and salesmen:

 

Guarente has never been entirely at ease with the adjacency of science and money. He left Elixir, his previous biotech effort, after seven years, having lost power to the company’s venture capitalists. They ended up “not wanting to work on anything science-based but wanting to just import stuff that was already being sold elsewhere in the world, marginally related to aging, and call that an anti-aging company,” he told me...

 

His disappointment with Elixir seems not to have tempered his enthusiasm for Elysium. As we talked, he sketched a vision of the new company’s future rich with possibility, bringing cutting-edge science to customers and contributing not just to the company’s bottom line but also to the greater social good. Elysium could, for instance, produce “the gold standard vitamin-D pill, and sell it basically at cost to get it out there.” [As if we need a gold standard vitamin-D pill... - DP] I asked him why his business partners would want to forfeit a profit. “They won’t,” he acknowledged. “It won’t turn out that way. ”

 

Buyers beware.

 

--Dean

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Right. For years and years now, I've been severely tempted to try a rapa+metformin combo - the only chemical intervention I have any hope for at all (never felt resveratrol or any previous compound was worth a hill of beans). Two things stopped me - no real studies in humans: tons of compounds that show effects in animals fail to translate to humans (both positive and negative); and lack of any evidence-based dosage regimen (which to a degree follows from the first objection, i.e. lack of documented positive effects in humans).

 

As the years pass, I feel increasing pressure to just roll the dice, because the older I get, the less time I have left for any chemical intervention to work its effect. What good does slowing aging even by a dramatic 50% do me, if my remaining LS is 1 year? 

 

And as odds for any decent human studies seem ever more remote, the more I am reduced to base gambling on little evidence. Not a happy position to find myself in, given my insistence on "first, do no harm" and "strictly evidence based". Sometimes all your choices range from bad to worse.

 

I'll continue holding off for now, and hope for the best.

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