I'm excited to see more studies done in this context, but without the HIV association. My wife has Ehlers-Danlos Syndrome and Rheumatoid Arthritis. She saw more benefits in inflammation reduction than weight reduction, especially those first two weeks she started taking it. She says her pain levels are night and day difference when on GLP-1 vs off. To me it would then make logical sense that reduced inflammation can have a measurably positive effect on aging.
Let's play spot the conflict of interest. Three of seven authors tied to a company selling biological aging tests. One consults for Merck, GSK, etc.
There seems some promise at times but I also struggle to see the recent slew of "GLP-1s cure X", where X is seemingly any ailment known to man, as much more than the next Big Pharma gold rush where the profits dwarf any eventual regulatory fines, and taxpayers and real patients are left with the costs.
You may be right that they are in a bind wrt public opinion. But that is not a defence against any specific criticism. What is your opinion on the conflict of interest mentioned above?
How is it a conflict of interest for GLP-1 makers and the scientists who work with/for them to look for new medical value in an academic setting with willing collaborators and all the usual peer review?
It's not but there's a lot of historical evidence that those situations are more likely to produce research that looks favorible to the sponsoring company. So it means you have to be a little more careful when looking at those results.
One thing they are spending them on is tons of new research. Lilly is spinning up massive facilities in Indiana, of all places. I know some absolutely fantastic researchers at Indiana University but I had never thought of it as a biotech hub before.
I am EXTREMELY skeptical of epigenetic clocks at the moment, and have been for a few years, but at the same time it's important for these clocks to be investigated and shown to be what they are.
Even though I personally expect them to be readouts of things that don't affect healthspan much, I don't have any more evidence than those trying to work out what they are. I've been wrong before, and also most tech development does not end up living to its promises, but without the investigation we'll never know.
> Big Pharma gold rush where the profits dwarf any eventual regulatory fines
With pharma malfeasance, the penalties are actually big enough, unlike most other fields. Unless you have something particular in mind?
it's low quality research. you don't need to point to perceived conflicts of interest. the drug is semaglutide, not a merck or gsk product. and semaglutide is coming of patent anyway
Every gram of body weight needs energy to stay alive. If you are in a caloric deficit, you will lose weight until your energy expenditure matches the caloric intake.
If you stay in "caloric deficit" forever you will actually starve by definition.
Properly defining what you mean (comparatively low caloric intake without defining it via the current weight) is actually quite tricky, as your height, body composition and physical activities are all inputs to what counts as a "normal" caloric intake.
>They also reduce visceral and ectopic fat that accumulates around the abdomen and organs, which may help curb the inflammatory and metabolic signals that promote aging.
Interesting, I wonder if someone will do a study where they pair a GLP-1 with tesamorelin to see if there's any synergy there in terms of fat reduction and reduced aging.
Not really, in most cases! I read up on the per-exposure chances of actually picking up HIV a while back[1] and was shocked at how low the risk is, especially for heterosexual men (4 in 10,000 per-exposure; insertive vaginal sex with an infected partner).
Even in the highest-risk scenario (receptive anal sex) the risk is ~138/10,000 per exposure.
pregnancy would seem rare too if you only looked at the averaged per-incident chances (swings from 0% to 33%ish for about 2 days for a perfectly healthy breeding-aged couple); or if you were to compare the amount of heterosexual sexual encounters overall to the amount of pregnancies.
but that's not really how the risk should be considered.
They work on that group because (as the article says) they show increased aging relative to a normal group, making it easier to detect effects in a relatively short running study.
I have never seen a user name better fit a hacker news comment.
This also perfectly sums up the whole emotional roller coaster of modern science communication.Oh that could be cool (title)... Hey this might be good work... Fuck thats depressing I will never get this time back.
This feels like the early days of medical marijuana where everything was sunshine and rainbows, and then 10 years later we realize yes, there are still drawbacks.
yes a weight loss drug for a country that is over 70% overweight is absolutely the same as a psychoactive drug with well-understood cognitive side effects and abuse risk, a perfect analogy
There is a gold rush happening where every health influencer, telehealth prescriber, and even aging services provider (as is the case with some of these study authors) is trying to push this medication for a wider audience.
Medical marijuana was different, though. The negatives were known medically before and after. The push was almost entirely political and on social media. The few places medical marijuana were medically pushed were either for highly specific applications or as a harm reduction measure: Either as an alternative for patients who demanded opioids (medical marijuana isn’t actually a viable substitute for opioids in severe high level pain, but it’s common for patients to demand to be prescribed something “stronger” for lesser conditions and there was a real problem with opioid over prescription at the time) or from the sector of medicine that sees that patients are seeking out drugs anyway and thought this was a better way to control and monitor it. The way it worked out in practice became a laughable loophole where anyone who wants a card can pay $100 for a meeting with a prescriber who will give leading questions until you say the right things to get the card, which wasn’t even what the original medical marijuana proposals were about.
In the medical and research world, there was never an illusion that marijuana was actually entirely harmless and without drawbacks, except for fringe papers and a few politically motivated researchers.
FDA approval of the first GLP-1 agonist was in 2005 and many diabetics have been taking these drugs for close to 20 years, so we have a pretty good picture of what long term side effects are: mostly GI symptoms, and you can have problems with muscle loss and bone weakening if you lose a ton of wieght. otherwise they are well tolerated.
Been on one for a few years now, it tempered my persistent auto-immune issues. Short term side effects are barely present for me. This stuff has made it so I don't have to be on steroids and antibiotics every other month. I did not start the medication for weight loss purposes, though have lost 10-15lbs, but I attribute that to being off steroids.
Long term? Who knows for sure. Semaglutide has been approved for 9 years. Liraglutide was 2009 and hasn't shown thyroid issues still. Exenatide has been available since 2005.
GLP-1s aren't new and haven't shown widespread negative issues beyond gastrointestinal upset, and that is typically fixed by... drinking more water. The trials in rats have pointed towards potential thyroid cancer risks but those haven't been seen in people.
There is reason to have some healthy skepticism for pharma. But I am sometimes astounded by how unshakably cynical people can be.
I suppose we all could wind up with cancer in 10 years or something hypothetically, due to some unforeseen mechanism. But here's my story.
I went from 200lb to 140lbs at 5' 9" over 3 years. I feel great. I don't need to eat 1000 calories before bed just to sleep through the night. I focus better at work. Blood pressure is back to normal. HDL is back to normal. I can run without joint pain. I feel good about myself. I feel comfortable going on dates. I'm not a near-obese shut-in loner that can't be in a caloric deficit without wrecking my sleep.
Unless there are literally fatal side effects, these drugs seem pretty miraculous.
In the UK you just fill in an online form. I don't think anyone is going to come and weigh you to double check what you put in the form is true. Almost zero oversight which is a bit shocking really.
If the DunedinPACE test is so accurate and cheap now, there must be hundreds of people that have a baseline and also measurements after taking GLP’s… also why do you need a double blind if you have this amazing biological ageing test?
If you're getting it compounded it may be time to switch providers.
Seriously, in the first week you should feel a bit of nausea at .25mg. After 2-3 weeks you should see something, either weight loss (most) or gain (some).
Or you could be one of those who have no effect, which sucks. I'd go over your process with your provider, from storage to injection.
Not everyone gets nausia. On .25 I had zero side effects. At .5 minor sulpher burps that lasted a few days and then again down to zero side effects. In the online communities of people on GPL-1 very few people have side effects.
Why on earth would having no side effects suck? As long as its working (weight loss) then thats the ideal scenario.
Nonetheless, Dr. Carvalho agrees with avoiding sugary drinks:
"We have a lot of recent evidence, recent studies after [Lustig's] talk. The link between soda and weight gain and obesity and other chronic diseases is quite strong."
Drink fewer sugary beverages, consume fewer calories (eat less), exercise, and drink less alcohol.
glp1 doesn't increase your basal metabolic rate, it curbs your appetite. so it's still possible to ingest an excess of energy and to maintain your energy storage volume if you continue the dietary habits that got you fat in the first place -- eating slop and/or eating for the sake of eating.
even one caffeinated corn syrup slurpee that people consume like it's no big deal can be a quarter or more of your daily energy requirement. a few snacks on top of that and that leaves preciously little budget for real food.
That's not a common side effect, and I've been watching GLPs for years. In fact, it's more likely to cause divorces due to, you know, becoming more attractive.
If two cars are each three years old, but one has had twice as much gas consumption as the other, which would you expect to show more wear on its comppnents?
Caloric churn is putting the body's systems through their paces - at the very least for everything related to digestion. But really most of life is well described as pieces of a metabolic process.
Comparisons like this, while seeming to make sense using “common sense” rarely impart any value or scientific meaning. Maybe it works like that, maybe it doesn’t.
If as a result of less caloric consumption you’re starving your cells of needed nutrients, maybe that’s the one that degrades earlier.
If a car sits idle for months at a time, its rubber seals and gaskets will degrade faster ... so, obviously, according to this bullet-proof analogy, a human that doesn't exercise will be in worse condition.
I'm excited to see more studies done in this context, but without the HIV association. My wife has Ehlers-Danlos Syndrome and Rheumatoid Arthritis. She saw more benefits in inflammation reduction than weight reduction, especially those first two weeks she started taking it. She says her pain levels are night and day difference when on GLP-1 vs off. To me it would then make logical sense that reduced inflammation can have a measurably positive effect on aging.
Just sharing to spread the good word: with my ex-wife also having EDS and rheumatoid arthritis, she saw a large benefit from low dose naltrexone.
https://www.ehlers-danlos.com/effective-doses-of-low-dose-na...
Let's play spot the conflict of interest. Three of seven authors tied to a company selling biological aging tests. One consults for Merck, GSK, etc.
There seems some promise at times but I also struggle to see the recent slew of "GLP-1s cure X", where X is seemingly any ailment known to man, as much more than the next Big Pharma gold rush where the profits dwarf any eventual regulatory fines, and taxpayers and real patients are left with the costs.
No matter what drugmakers spend money on, you hear complaints:
- Marketing, to learn what / whom / how to sell: “They spend more on TV ads than R&D!”
- Basic R&D: “Look at all the conflicts of interest in this academic research!”
- Commercial R&D: “They’re just looking for ways to extend the patent lifetime of drugs that only exist because of government-funded basic R&D!”
- Back to the shareholders (mostly pensions and retirement accounts): “Billions of stock buybacks for Wall Street!”
What should the pharmaceutical companies with billions coming in from GLP-1’s be spending their money on?
What’s the concern here? Too much justice? Holding powerful institutes to account frequently seems like a good thing to me.
You may be right that they are in a bind wrt public opinion. But that is not a defence against any specific criticism. What is your opinion on the conflict of interest mentioned above?
How is it a conflict of interest for GLP-1 makers and the scientists who work with/for them to look for new medical value in an academic setting with willing collaborators and all the usual peer review?
It's not but there's a lot of historical evidence that those situations are more likely to produce research that looks favorible to the sponsoring company. So it means you have to be a little more careful when looking at those results.
What evidence are you talking about? Do you think industrial scientists collaborating with academics and vice-versa is unusual?
One thing they are spending them on is tons of new research. Lilly is spinning up massive facilities in Indiana, of all places. I know some absolutely fantastic researchers at Indiana University but I had never thought of it as a biotech hub before.
Lilly is headquartered in Indiana so it isn’t some huge surprise..
I am EXTREMELY skeptical of epigenetic clocks at the moment, and have been for a few years, but at the same time it's important for these clocks to be investigated and shown to be what they are.
Even though I personally expect them to be readouts of things that don't affect healthspan much, I don't have any more evidence than those trying to work out what they are. I've been wrong before, and also most tech development does not end up living to its promises, but without the investigation we'll never know.
> Big Pharma gold rush where the profits dwarf any eventual regulatory fines
With pharma malfeasance, the penalties are actually big enough, unlike most other fields. Unless you have something particular in mind?
> I am EXTREMELY skeptical of epigenetic clocks
I hear that word and I immediately think of "that" guy that runs the cocktails of additive interventions to "improve" it.
Yes, I hear what you’re saying… Let me tell you about peptides!
it's low quality research. you don't need to point to perceived conflicts of interest. the drug is semaglutide, not a merck or gsk product. and semaglutide is coming of patent anyway
I don't understand this fixation. If you literally had a cure for X for X in all ailments known to man, you would in fact have a Pharma gold rush.
Isn't being "underweight" generally shown to reduce the speed of aging
Yeah but that's hard, they need the magic pill
Yes, people have been trying this the "old fashioned way" since the 90s https://en.wikipedia.org/wiki/CRON-diet
Came here to say this. Also caloric deficits.
I saw reports on that before the GLP1 craze. Calorie reduced diets for lab animals generally increased their life span.
Probably you both really mean the same thing.
Every gram of body weight needs energy to stay alive. If you are in a caloric deficit, you will lose weight until your energy expenditure matches the caloric intake. If you stay in "caloric deficit" forever you will actually starve by definition.
Properly defining what you mean (comparatively low caloric intake without defining it via the current weight) is actually quite tricky, as your height, body composition and physical activities are all inputs to what counts as a "normal" caloric intake.
I thought caloric deficits lead to starvation.
>They also reduce visceral and ectopic fat that accumulates around the abdomen and organs, which may help curb the inflammatory and metabolic signals that promote aging.
Interesting, I wonder if someone will do a study where they pair a GLP-1 with tesamorelin to see if there's any synergy there in terms of fat reduction and reduced aging.
> slows down the accumulation of biological aging markers in the DNA of adults with HIV
And if you don’t have HIV?
Easy to pick it up
I thought I was on Reddit for a split second
Not really, in most cases! I read up on the per-exposure chances of actually picking up HIV a while back[1] and was shocked at how low the risk is, especially for heterosexual men (4 in 10,000 per-exposure; insertive vaginal sex with an infected partner).
Even in the highest-risk scenario (receptive anal sex) the risk is ~138/10,000 per exposure.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC6195215/
pregnancy would seem rare too if you only looked at the averaged per-incident chances (swings from 0% to 33%ish for about 2 days for a perfectly healthy breeding-aged couple); or if you were to compare the amount of heterosexual sexual encounters overall to the amount of pregnancies.
but that's not really how the risk should be considered.
> randomized, placebo-controlled clinical evidence
:)
> data from a...clinical trial of 108 adults with HIV associated lipohypertrophy
:(
They work on that group because (as the article says) they show increased aging relative to a normal group, making it easier to detect effects in a relatively short running study.
Why the sad face?
Title of the post hints to a generalization. Study otherwise is pretty specific in the group of people being studied.
I guess I've become so used to the Science News Cycle that I'm not even surprised when I see it behave like this:
https://phdcomics.com/comics/archive.php?comicid=1174
This, and also it's a pitifully small sample size regardless.
> howunfortunate
I have never seen a user name better fit a hacker news comment.
This also perfectly sums up the whole emotional roller coaster of modern science communication.Oh that could be cool (title)... Hey this might be good work... Fuck thats depressing I will never get this time back.
This feels like the early days of medical marijuana where everything was sunshine and rainbows, and then 10 years later we realize yes, there are still drawbacks.
yes a weight loss drug for a country that is over 70% overweight is absolutely the same as a psychoactive drug with well-understood cognitive side effects and abuse risk, a perfect analogy
There is a gold rush happening where every health influencer, telehealth prescriber, and even aging services provider (as is the case with some of these study authors) is trying to push this medication for a wider audience.
Medical marijuana was different, though. The negatives were known medically before and after. The push was almost entirely political and on social media. The few places medical marijuana were medically pushed were either for highly specific applications or as a harm reduction measure: Either as an alternative for patients who demanded opioids (medical marijuana isn’t actually a viable substitute for opioids in severe high level pain, but it’s common for patients to demand to be prescribed something “stronger” for lesser conditions and there was a real problem with opioid over prescription at the time) or from the sector of medicine that sees that patients are seeking out drugs anyway and thought this was a better way to control and monitor it. The way it worked out in practice became a laughable loophole where anyone who wants a card can pay $100 for a meeting with a prescriber who will give leading questions until you say the right things to get the card, which wasn’t even what the original medical marijuana proposals were about.
In the medical and research world, there was never an illusion that marijuana was actually entirely harmless and without drawbacks, except for fringe papers and a few politically motivated researchers.
It says 42% of treatment group showed slower aging, and reduction in telomere length... is there an effect size published anywhere?
Presumably mediated by caloric intake reduction, which is already known to slow aging?
I'd be more suspicious of what side effects this thing has.
FDA approval of the first GLP-1 agonist was in 2005 and many diabetics have been taking these drugs for close to 20 years, so we have a pretty good picture of what long term side effects are: mostly GI symptoms, and you can have problems with muscle loss and bone weakening if you lose a ton of wieght. otherwise they are well tolerated.
Been on one for a few years now, it tempered my persistent auto-immune issues. Short term side effects are barely present for me. This stuff has made it so I don't have to be on steroids and antibiotics every other month. I did not start the medication for weight loss purposes, though have lost 10-15lbs, but I attribute that to being off steroids.
Long term? Who knows for sure. Semaglutide has been approved for 9 years. Liraglutide was 2009 and hasn't shown thyroid issues still. Exenatide has been available since 2005.
GLP-1s aren't new and haven't shown widespread negative issues beyond gastrointestinal upset, and that is typically fixed by... drinking more water. The trials in rats have pointed towards potential thyroid cancer risks but those haven't been seen in people.
There is reason to have some healthy skepticism for pharma. But I am sometimes astounded by how unshakably cynical people can be.
I suppose we all could wind up with cancer in 10 years or something hypothetically, due to some unforeseen mechanism. But here's my story.
I went from 200lb to 140lbs at 5' 9" over 3 years. I feel great. I don't need to eat 1000 calories before bed just to sleep through the night. I focus better at work. Blood pressure is back to normal. HDL is back to normal. I can run without joint pain. I feel good about myself. I feel comfortable going on dates. I'm not a near-obese shut-in loner that can't be in a caloric deficit without wrecking my sleep.
Unless there are literally fatal side effects, these drugs seem pretty miraculous.
>I suppose we all could wind up with cancer in 10 years or something hypothetically
Extremely unlikely, GLP-1 receptor agonists have been on the market for more than 20 years now, exenatide being first used in 2005.
It would be pretty funny if it turns out it doesn't have any side effects and it really is just a silver bullet.
you already feel it. we live in a chaotic world which is a consequence of people, especially those with power, live longer than their predecessors.
I, for one, do not welcome our basically-inmortal AI overlords-to-be.-
a cruel destiny for humanity.
Controlled by increasingly unfeeling, sociopathic masters, who grow more and more in power. And now also do not age or get sick.
The power those at the top hold far exceeds any king or emperor throughout humanities history.
Ok, can you list which diseases and conditions we should not be trying to treat because evil rich people would benefit?
They used to poison themselves with mercury, in search of something the disembodied few will have. Black Mirror as a PSA fell short.-
Its been decades since it was invented so perhaps we'll find out soon.
but what about the people with a BMI already under 20?
not like we can take GLP-1 even if it was affordable
btw soluble fiber helps people naturally secrete more GLP-1 but of course not on the same level as a dedicated drug
What's preventing you from taking a GLP-1 with a BMI under 20? I started semaglutide with my BMI at 19.
How did you get your prescription?
In the UK you just fill in an online form. I don't think anyone is going to come and weigh you to double check what you put in the form is true. Almost zero oversight which is a bit shocking really.
If you don't have diabetes, it would be off label use in that case, which is not illegal.
Once at optimal bodyfat/weight afaik CRON diet is the long term solution?
If the DunedinPACE test is so accurate and cheap now, there must be hundreds of people that have a baseline and also measurements after taking GLP’s… also why do you need a double blind if you have this amazing biological ageing test?
why wouldn't you need a double blind?
scy hub link? anyone?
Jesus Christ is there anything this thing can’t do?
I have been injecting this stuff for months now with no weight loss
If you're getting it compounded it may be time to switch providers.
Seriously, in the first week you should feel a bit of nausea at .25mg. After 2-3 weeks you should see something, either weight loss (most) or gain (some).
Or you could be one of those who have no effect, which sucks. I'd go over your process with your provider, from storage to injection.
Not everyone gets nausia. On .25 I had zero side effects. At .5 minor sulpher burps that lasted a few days and then again down to zero side effects. In the online communities of people on GPL-1 very few people have side effects.
Why on earth would having no side effects suck? As long as its working (weight loss) then thats the ideal scenario.
I think you still have to eat less.
Robert Lustig's Sugar: The Bitter Truth hammers on fructose being a major culprit to weight gain:
https://www.youtube.com/watch?v=dBnniua6-oM
Dr. Gil Carvalho (medical doctor, research scientist, science communicator) debunks parts of Lustig's 30-year-old claims:
https://www.youtube.com/watch?v=vdoDx9dIuNE
Nonetheless, Dr. Carvalho agrees with avoiding sugary drinks:
"We have a lot of recent evidence, recent studies after [Lustig's] talk. The link between soda and weight gain and obesity and other chronic diseases is quite strong."
Drink fewer sugary beverages, consume fewer calories (eat less), exercise, and drink less alcohol.
Luckily, like exercise, there are cardiovascular benefits even without weight loss.
https://www.medicalnewstoday.com/articles/weight-loss-drug-h...
One of my reports at work started out with heavy diabetes and 300 pounds. Now he’s down to under 200 and has no diabetes less than 5 months later.
Why are you continuing then
glp1 doesn't increase your basal metabolic rate, it curbs your appetite. so it's still possible to ingest an excess of energy and to maintain your energy storage volume if you continue the dietary habits that got you fat in the first place -- eating slop and/or eating for the sake of eating.
even one caffeinated corn syrup slurpee that people consume like it's no big deal can be a quarter or more of your daily energy requirement. a few snacks on top of that and that leaves preciously little budget for real food.
Of course it does. /s
How much are the pharma companies paying people to project this nonsense to trick people to take these drugs to make money out of it?
This is the new grift.
They also cause sexual dysfunction while you're taking them. Not a problem I guess when you're overweight, but on weight...it's a huge problem.
Or put another way, "Let me pluck one of the rare side effects and make it seem like its a common one because I know nothing about this"
That's not a common side effect, and I've been watching GLPs for years. In fact, it's more likely to cause divorces due to, you know, becoming more attractive.
If two cars are each three years old, but one has had twice as much gas consumption as the other, which would you expect to show more wear on its comppnents?
Caloric churn is putting the body's systems through their paces - at the very least for everything related to digestion. But really most of life is well described as pieces of a metabolic process.
Comparisons like this, while seeming to make sense using “common sense” rarely impart any value or scientific meaning. Maybe it works like that, maybe it doesn’t.
If as a result of less caloric consumption you’re starving your cells of needed nutrients, maybe that’s the one that degrades earlier.
This is such an oversimplification of complex biological processes that it borders on medieval superstition.
Should we similarly expect those who use their muscles more to be in worse condition than someone who doesn’t exercise?
If a car sits idle for months at a time, its rubber seals and gaskets will degrade faster ... so, obviously, according to this bullet-proof analogy, a human that doesn't exercise will be in worse condition.
Oxygen is a reactive species, that's how we do what we do. How we swim the thermodynamic eddies and flows across quadrillions of chemical reactions.
But burning that fuel is damaging.