Combination of Rapamycin and Acarbose significantly Extends Lifespan

https://www.lifespan.io/news/combination-of-rapamycin-and-acarbose-extends-lifespan/

by evo_9 • 4 years ago

98 77 4 years ago

lifespan.io

olliej• 4 years ago

Please add the expected [in mice] mysteriously missing from the headline itself

eruleman• 4 years ago

Props to the authors for choosing the subheader: "This effect was shown in mice."

ahazred8ta• 4 years ago

dose: mice were fed a diet containing 14 ppm rapamycin (mTOR antibiotic) and 1000 ppm acarbose (diabetes drug) for three months

ck22• 4 years ago

They've been studying Acarbose for awhile now

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789153/

The problem with a lot of these longevity approaches is they "solve the problem" by reducing energy conversion, like acarbose, pulling people to a baseline and preventing stress adaptations.

Great for sitting around. The opposite of that for doing anything athletic, you'd never improve.

thebeastie• 4 years ago

What does that mean, preventing stress adaptations? Does it mean that the body wouldn’t get stronger in training ?

nradov2• 4 years ago

Right. Some of these potential longevity interventions seem to have a catabolic effect. Not a problem if you're a mouse living in a safe, flat lab cage. But problematic for an elderly human at risk of falling down the stairs and breaking a hip due to sarcopenia.

thornjm• 4 years ago

There is some evidence that "aerobic exercise" itself produces an equivalent baseline energy deficit without the performance downside.

This guy[0] studies total average energy expenditure over time and demonstrates that an athlete undertaking intense regular exercise uses marginally more energy over time than someone sitting on a couch all day. The hypothesis being that the athlete is conserving energy by down-regulating baseline metabolic and inflammatory processes when at rest.

Disappointing news for "exercise causes dramatic weight loss" but encouraging news for "exercise is anti-cancer" (a correlation demonstrated many times I believe).

[0] https://www.science.org/content/article/scientist-busts-myth...

ehnto• 4 years ago

I have seen this study before, but I can't see how this gentleman's work disproves the huge body of health and fitness research that comes before it. It's an interesting outcome for sure, but the idea that it suggests exercise is a bad weight loss tool doesn't seem to reflect reality. The long term outcome of exercise is a changed body composition, which itself can contribute to changing metabolic rates.

I think it points to an interesting insight, something we have yet to uncover perhaps, but I don't think it disproves that exercise spends energy. Maybe all it's really proving is that we are very efficient at the chosen type of exercise in the study.

ck22• 4 years ago

Exercise causes weight loss only in that as you want to get more fit you start watching what you eat, quality and quantity, more carefully.

As a lifelong runner I know I only burn 80 calories or less per mile, that's nothing.

However exercise does things that no supplement or drug can do, proper AMPK and cAMP activation, endorphin and endocannabinoid release.

hinkley4• 4 years ago

I have just gotten my resting heart rate back down to pre-quarantine levels. I don’t know how many days I shaved off my lifespan from all that sitting around, but I’m a little bitter about it.

hericium• 4 years ago

Previous links and discussions on Rapamycin and Metformin:

Rapamycin, drug used in cancer therapy, emerges as powerful anti-aging remedy [1]

Rapamycin extends life span and health span of male mice and Daphnia magna [2]

Drug typically used in cancer therapy emerges as potential anti-aging treatment[3]

Diabetes Drug Metformin Reduces All-Cause Mortality and Diseases of Aging (2017)[4]

Metformin for cancer prevention, longevity: popular in Silicon Valley[5]

[1] https://news.ycombinator.com/item?id=32660669

[2] https://news.ycombinator.com/item?id=33058322

[3] https://news.ycombinator.com/item?id=32648886

[4] https://news.ycombinator.com/item?id=27486841

[5] https://news.ycombinator.com/item?id=19472942

ChrisGranger• 4 years ago

My understanding is that Metformin's mortality reduction effect is only present in younger people. I don't have a source handy, but I take it for diabetes and was reading about its other positive effects a few years ago. Perhaps someone can chime in with additional information.

graderjs3• 4 years ago

I'm interested in how ultra-low-dose (or "sparse" regimens) affect things (before you get triggered by homeopathy, I'm not making regard to that here..tho doesn't mean in some cases it can't be effective). For example, ultra low dose minoxidil (a blood pressure drug) reverses hair loss in many people (not if you're totally bald, but in thinning areas) at dosages where it's "on-label" effect (lowering blood pressure) doesn't even occur. I wonder how ultra-low-dose (or sparse, like "1 timer per quarter") metformin affects things.

I can't recall the compound now, but I recall seeing something the other day about: "encounter with compound X just one time permanently strengthens immune system" or something. I think it was also in mice. I'm not even sure it was "immune system".

Also want to note that: our current pharmaceutical industry of (mostly) single molecule therapies is just one slice of the pie. In the future, we will probably have access to therapies that seem really sophisticated: not just "concoctions" (of multiple compounds in one therapy, which currently we are not sophisticated enough to explore sufficiently so the space of possible interactions that are therapeutic remains unknown); but also more "active" therapies, that include some vector (like virus, protein molecular machine, funghi, bacteria) that help to deliver / manufacture the therapy to just the right: time, location, amount our body needs.

And rather than being a specialized minority, they will be the majority. I think the space of molecules that are effective when delivered "systemically" is not as large or contains as many "silver bullet therapies" as the space of therapies that is effective when delivered precisely.

graderjs3• 4 years ago

Rapamycin side effects don't look great tho: https://en.wikipedia.org/wiki/Sirolimus#Adverse_effects

I prefer drugs that are: well-tolerated, cheap, already have a long history of use for conditions X, Y and Z, and then discovered as an off-label therapy (maybe in combination) for something else. As a heuristic it may not always work, but I think a good sign / rule-of-thumb might be "on the WHO list of essential medicines"

jokowueu4• 4 years ago

You won't do it at the same doses as cancer treatment protocols .

I've been doing rapa for my mood issues stemming from inflammation for some years now and low doses similar to the doses seen in recent studies for age longevity with no apparent side effects .

29athrowaway• 4 years ago

Better than dying of old age though.

hombre_fatal• 4 years ago

Metformin doesn't look so hot either: https://www.science.org/content/article/rare-genital-defects...

snvzz2• 4 years ago

If you hate aging (who doesn't), SENS Foundation[0] is dedicated to engineering solutions to reverse it.

0. https://www.sens.org/

xiphias2• 4 years ago

People in SENS kicked out Aubrey de Gray for a ,,grooming” email and took over control of the donations that were sent because of him. I do not condone his previous action, but I also think that kicking him out to take over millions of dollars was not an unselfish action.

He is in the process of setting up a new foundation where I expect most of the new donations will flow.

snvzz2• 4 years ago

There was some drama[0], but did they really[1]?

I guess there's his twitter account[2]. Wow.

0. https://en.wikipedia.org/wiki/Aubrey_de_Grey#Sexual_harassme...

1. https://www.sens.org/about-us/leadership/

2. https://twitter.com/aubreydegrey

givemeethekeys• 4 years ago

Someone should inform the lab mice that they'll be living longer than before.

revolvingocelot• 4 years ago

I don't think we should burden them in that way. It's hard enough being a lab mouse as it is.

el_nahual• 4 years ago

Like the joke says, if you're a mouse and still have cancer, diabetes, or Alzheimer's, you need a new agent.

sitkack• 4 years ago

I am currently undergoing gene therapy to turn into a mouse. All my problems are solved.

realkiddredd• 4 years ago

Totally misleading headline

sciencemajor• 4 years ago

Rapamycin is a potent immunosuppressor... yikes.

Blammar• 4 years ago

Guess we'll figure out how to make mice immortal sometime soon, and sadly realize that the drug cocktail doesn't work on humans. Then the meek mice take over the earth as humanity dies off...

Reason077• 4 years ago

Presumably the mice would still need humans to keep producing the drugs that keep them immortal. But if immortality was a genetic trait passed on to their offspring then we’d be in trouble!

kiawe_fire• 4 years ago

This future is oddly more comforting to me than Skynet.

criddell• 4 years ago

And dogs too!

https://dogagingproject.org/

seydor• 4 years ago

Is there progress in the research to transition from human to mouse?

melonrusk• 4 years ago

https://archive.ph/Uaeza

elromulous• 4 years ago

I think at this point not putting "in mice" in an article title like this is just dishonesty.

iopq• 4 years ago

I just went straight to the comments looking for "in mice", not disappointed

slazaro• 4 years ago

I "yelled" IN MICE right after reading the title, went to check the article, and sure enough...

But yeah, it seems 100% deliberate because most people wouldn't probably care after reading the title. It's academic clickbait techniques.

adrian_b3• 4 years ago

To be fair, there is little choice for any such study to be done on anything else but mice, because of their short natural lifespan.

Even if there were human volunteers willing to test on themselves various cocktails of chemicals, such a study would take many centuries.

Also on monkeys any study would take much too long.

So until aging in mice is well understood, any tests on monkeys or humans are pointless.

It is unlikely that the aging mechanisms differ in an essential way between mice and humans. If the aging in mice were understood, finding how it functions in humans would need far less work than for discovering how it functions in mice.

Eddy_Viscosity2• 4 years ago

The problem wasn't that the study was done on mice, it was that this piece of information out was left out of the title. I agree with the OC that its deliberatively deceptive, unless of course this article was in 'The Journal of Mice' in which case it would be ok.

JoshTko• 4 years ago

Your last point needs to be emphasized more. The core mechanism of aging is likely to be very similar across species as aging affect all tissues, organs, etc.

kevinventullo• 4 years ago

It is unlikely that the aging mechanisms differ in an essential way between mice and humans.

[citation needed]

tomohawk2• 4 years ago

I get why people are facinated by this sort of research, but pick your favorite nasty person, such as Putin, and consider what it would mean to radically extend their life.

People in in Congress (an oxymoron) would be there even longer as they generally have to die to get kicked out. The longer they're there, the less they care about you and the more they'll care about their long lived fellow travelers.

herbst• 4 years ago

Says more about the broken system(s) then the danger of long life's.

tomohawk2• 4 years ago

What systems are not broken?

dsq• 4 years ago

I remember there being a lot of noise a few years ago about resveratrol, and how red wine (but only of a certain grape) was the secret to long life. What happens if you make the wrong decision and go all in, drinking wine and gobbling grape seeds, while it turns about to be something else entirely and you missed the boat? There’s no end to it, especially as there are only two real solutions that work, extreme caloric restriction and young blood transfusions(i.e a personal “blood boy”, humorously depicted in HBO’s Silicon Valley).

lambdafourtwo3• 4 years ago

rapamycin triggers the same effect as extreme caloric restriction. Neither of the solutions you mentioned have been scientifically verified in humans.

Longevity research itself hasn't been around long enough to verify ANY longevity hypothesis on humans.

jtbayly2• 4 years ago

… in spite of being around for millennia.

s1k3• 4 years ago

If genuinely interested and not being tongue in cheek, there are a number of drugs and pathways that can be targeted to (in theory) extend lifespan in mammals. So as others have said- it may be that future therapies include a concoction of drugs and interventions to effectively increase lifespan in humans. If you’re curious about the subject Dr. David Sinclair does a lot content around this. He’s a researcher in the longevity field. He’s a little out there in terms of his personal beliefs but he does provide a lot of inform and context around all the current hot topics in longevity research.

jeroenhd• 4 years ago

Whenever these immortality drugs come up, I always envision some kind of old, rich guy who dedicated his life to becoming rich, finding out that all that money won't buy you a second youth when it's already too late to do all the things he wanted to do. Multi millionaires getting rich, forgetting to live, and then focusing their wealth on a pipe dream of living long enough to spend all their money.

Ever since the first days of medicine, people have sought to prolong life. I think the entire quest is misguided and a waste of the medical field's resources; finding the cure for cancer and other horrible diseases should have priority on making some chosen few live to 100.

Even if the drug does work on humans without making life worse through side effects, I think the end result will be quite dystopic. You end up with a drug the rich can afford quite handily, while the poor will need to work their asses off for decades longer. Unless the drug is free, this will only serve benefit the top 1% of the planet and the pharmaceutical companies selling these drugs. As mankind struggles to accept mortality, the pool of workers will grow, led by drug companies telling them just a few decades years of hard work will surely make them rich.

staticassertion2• 4 years ago

If you were drinking red wine for resveratrol you were not doing much research.

gdudeman• 4 years ago

I want to add some nuance to this:

Resveratrol probably doesn’t do anything. This same research group actually studied it on mice. If you were gobbling it, you’re neutral. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598361/

Young blood transfusions may work, but the research is certainly still thin. Interestingly, removing old blood seems to be the actual benefit, not the addition of young. Source: https://www.science.org/content/blog-post/young-blood-and-ol...

Extreme caloric restriction reduces lifespan, but there does seem to be a sweet spot of restriction that lengthens it.

None of these things are proven in humans however and we don’t really know the side effects. Do they give you dementia? Do they make you dumb? Unlikely, but we just don’t know.

BLKNSLVR• 4 years ago

Low effort post, but, it's almost as if we're working towards this end game: https://youtu.be/y5xcvAoKojo?t=223

Stevvo• 4 years ago

To me it does look a bit comically like searching for the philosopher's stone as an ancient alchemist. If it's found within your natural lifetime you will be dead before the research is complete; by definition it will take longer than an average human lifespan. Mice only live a year so they are pretty quick and easy to study.

amelius• 4 years ago

Or become a test subject and get lucky.

staticassertion2• 4 years ago

If it's found within your natural lifetime you will be dead before the research is complete

I'm 30. If it takes another 30 years, I'll be 60. That's late, certainly, but I could still avoid a lot of health issues if I'm able to start taking something then. Most older people I know really start to degrade around their 70s and 80s, often after some sort of health incident or chronic issue crops up.

And if not, ok, well then some younger people in a generation or two will benefit and I'm happy for them.

dominotw• 4 years ago

Rapamycin is the word I keep hearing in 'health and wellness' communities online and on podcasts.

I think this guy is the most vocal about it

https://peterattiamd.com/rapamycin-risks/

https://twitter.com/mkaeberlein/status/1428740546177105922

hinkley4• 4 years ago

I’m very confused. Rapamycin upregulates autophagy, which is a popular theory about strengthening the body by killing the weak cells. Ok. But it’s prescribed as an anti-rejection drug. Those two things don’t dovetail in my mental model.

Combination of Rapamycin and Acarbose significantly Extends Lifespan

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