Having no inflammation at all is a very bad thing. Too much inflammation is also a very bad thing. Hypothetically, there's an optimal level of inflammatory response. Evolution doesn't necessarily guarantee that, at least when it comes to a single mouse.
An individual organism surviving for the longest amount of time is not necessarily optimal at the species level. It could be that mice (for instance) have a bit too high of an IL-11 response, but there's either no evolutionary pressure against it or there's some species-level value to it.
Above all, since only one interleukin was targeted in the research, we can't assume that all inflammation is bad and that no inflammation is ideal.
On a related note, I wonder if there's anything commercially available that can suppress IL-11. Currently, I'm taking phycocyanin extracted from spirulina, which is supposed to suppress COX-2 and IL-17, but I don't see any research confirming whether it has an effect on IL-11. Would be cool if I've unwittingly begun extending my lifespan. :D
> An individual organism surviving for the longest amount of time is not necessarily optimal at the species level.
Though it can be argued that among social, intelligent creatures, living grandparents holds value for the species. Humans and orcas both seem to benefit from them in many ways.
I would imagine that if humans were immortal, the centralization of wealth and power under a few families would be even more extreme. Which is probably not good for the vast majority of humans.
I'd rather have the healthy and energy of a 25 year old and live in a world where there are people far richer than me than be a frail 80 year old where at least I know there aren't any trillionaires.
Another thought I had was that revolutions over inequality almost always happen when there's a large youthful population. The old just don't have the energy or the future-focused outlook for big change. Inequality might be less stable if all adults had the health of their youth.
> I'd rather have the healthy and energy of a 25 year old and live in a world where there are people far richer than me than be a frail 80 year old where at least I know there aren't any trillionaires.
That's a very specific scenario, where everything happens to be going great for you. Do you honestly believe wealth inequality has no negative consequences for those at the bottom?
No, I agree that extreme wealth inequality is not desirable. But the question I'm trying to get at is if we can have medicine that will make people live dramatically healthier lives isn't it worth it even if some billionaires get to hold onto their wealth a little longer?
"But if we cure aging won't that mean that the ultra-rich will never go away??" That's what these conversations always seem to devolve into and it seems to miss the bigger picture.
I think it will be worth it, but we can't just assume that such a medicine will be available for everyone, or ignore the effects it will have on society.
Many medicines and treatments we have today are already basically available only to the wealthy.
Many prominent billionaires are on record spreading overpopulation FUD and anti-natalism, while having multiple children themselves.
In theory - I agree that having some kind of anti-aging treatment that is available for everyone would be awesome, but in practice it could end up as immortality for the very few, while making the vast majority worse off.
If they were immortal they'd soon find a way to move beyond this planet, then beyond this solar system. Once that is accomplished there is a whole universe to colonise so I assume that is what would happen. It would be the only way really since the planet would otherwise quickly fill up and 'immortality' would end up a pipe dream due to endless conflict over land and sustenance.
With an average fertility rate of 1, which is higher than that of many countries including where I live, even complete immortality would lead to an asymptotic population. Since some people will still inevitably die in accidents even if aging is solved, a fertility rate of 1 would be a declining population even with unlimited lifespans.
You're assuming everyone gets the immortality and is de facto benevolent. If you actually look at how the super rich and powerful have acted historically - its much more likely that the few richest/most powerful people would just take control of the earth, reserve immortality for themselves, and keep everyone else as a mortal slave.
Even if you were right, I'd still chose that society over death. I am not convinced though, wealth seems to dissipate over long periods (e.g. most billionaires today did not inherit their wealth).
Largely because it gets split amongst inheritors and they often are less able to manage wealth than the original accumulator of the wealth. Immortalis would not need to split their estate up every so often as death causes to happen now instead they would continue to accumulate more.
I mean, it's pretty hard to predict what such a society would look like, but it's plausible you'd just be a slave from birth until death (because poor slaves don't get the immortality pill).
> I am not convinced though, wealth seems to dissipate over long periods (e.g. most billionaires today did not inherit their wealth).
The single most reliable predictor of wealth BY FAR is being born into wealth. And arguably, it dissipates because it gets decentralized as it gets split up between heirs as it passed down to future generations which are typically less ambitious and focused on maintaining that power and wealth.
Imagine if Ghengis Khan, Stalin, Mao, Rothschild, Rockerfeller, all of the kings/royals/despots/dictators were immortal and still running the world - I don't think most people would want to live in that world.
> The single most reliable predictor of wealth BY FAR is being born into wealth.
I highly doubt that. I would guess that income and age would be much better predictors for example.
> I don't think most people would want to live in that world.
I would, if the other option was death.
Regardless, I doubt any of them would still rule the world had they not died of old age. Regimes survive despite the death of their rulers and fall while their rulers are still alive.
> I highly doubt that. I would guess that income and age would be much better predictors for example.
I'm talking about predictors of wealth for a new person. The age and income are both zero. If you have their income - you probably have their wealth already as well - nothing to predict.
And for the record, coming from wealth is the strongest predictor of future wealth. [0][1]
> I would, if the other option was death.
But you have no choice/option in my hypothetical scenario - you're born a slave and you die...
> Regardless, I doubt any of them would still rule the world had they not died of old age.
Really.... ? Why? All of the people I mentioned, maintained and grew their wealth/power their entire life up until their death. Having power/wealth is just a huge advantage if you're trying to gain/maintain power/wealth.
> I'm talking about predictors of wealth for a new person.
That's almost a tautology then. If you only know one thing about someone, that's also necessarily the best predictor for anything about them. However, it doesn't tell us much about whether wealth does concentrate over time.
> Really.... ? Why?
Because regimes change all the time despite rulers being alive. The death of a ruler by old age rarely triggers regime change, they just get succeeded by someone else. It's usually another event that triggers regime change (peaceful and violent revolutions, war, etc.). Immortal rulers wouldn't be immune to those events.
You can know a great deal about someone at birth, such as race, gender, country of origin, eye color etc. Yet you can accurately predict someone’s wealth at age 60 by looking at their parent’s wealth even though a babies income is generally 0.
Further wait until someone’s 10 and you can measure IQ, grades, etc and parents wealth is still #1. Wait even longer and high school GPA still isn’t nearly as useful.
The biggest cause of regime change seems to be the succession of power and the fears around change occurring during succession of power. A ruler dying through old age is a common source of regime change in history as people with varying interests start vying for that position and ensuring the new ruler holds their same interests.
I mean, I gave you multiple examples of some of the most powerful people that ever lived, none of which fall into this category you call the 'norm'. You just completely ignored that and continued with your baseless fantasy.
Upon his death, Genghis Khan was succeeded by his son. Mao was succeeded by Hua Guofeng, vice chairman of the CCP. Stalin was succeeded by Nikita Khrushchev, First Secretary of the Communist Party of the Soviet Union.
> If you only know one thing about someone, that's also necessarily the best predictor for anything about them.
Except it's not the only thing you know about them... so your point is kinda meaningless.
> However, it doesn't tell us much about whether wealth does concentrate over time.
There are soooo many studies supporting this, like the two I linked above, not to mention common sense.
It's like the most basic game theory + common sense - you have X people competing with each other, you give (0.001 * X) of those people massive advantages - who do you think is going to be winning?
In the United States, the single most determinative factor for lifetime earnings and life expectancy is the zip code you were born in and grew up in, up to age 13 or so.
Selection only cares about reproductive fitness of individuals. There is some weak evidence that grandparents can improve their reproductive fitness by supporting the fitness if their progeny. Any species level effects are not important players, although as our technological competence grows, this is likely to change.
> Though it can be argued that among social, intelligent creatures, living grandparents holds value for the species.
This is taken to an extreme in Larry Niven's "known space" setting. There's a bunch of interesting stuff I won't mention because spoilers, but imagine a very-humanoid race where the adults are not intelligent, but later they lose the ability to reproduce and gain hyper-intelligence, strength, and a ruthless drive to protect and advance their descendants.
>Humans and orcas both seem to benefit from them in many ways.
For a second, I thought you wrote "humans and orcs..." I don't think orcs really value grandparents that much, but who knows: Tolkein might have completely maligned them as mindless monsters when they were in fact just a fast-growing pre-industrial civilization.
A way to look at this is that death is an evolutionary advantage for the species. Vertebrates have a PVN that control the HPA-Axis. As anything that contributes to the HPA-Axis such as pain, stress, or inflamation increases, the PVN shrinks and it fairly rapidly (evolutionary wise) behaves like a kill switch to the brain. Some pre-Vertebrates can effectively live forever and the mammals that live the longest have different hpa-axis loops. What is wild to realize is that there was probably a creature at some point that wouldn't die from pain until that was connected to this loop.
Inflammation is typically experienced when the body is responding to an infection or injury. It is a normal, and as per current understanding, a necessary part of the body's immune response.
The Cleveland clinic has a nice, informative page if you want more information [0]
[edited to add]
The response of the innate immune system to the infectious agent / injury is what causes inflammation - i.e., for instance, fever, swelling, etc. It is a very very complex multi-cascade process, but one of the first responses to an injury, for instance, is the release of signalling molecules that results in localised swelling, slightly elevated temperature (which makes the tissue a little more inhospitable to bacteria / viruses), etc. all of which serve as the front line defense. <This is a severe over-simplification> Wikipedia has a good explanation that goes into the roles and triggers of the inflammatory response. [1]
Acute inflammation in response to infections and injuries is a good thing, and from everything we know, it is a necessary part of the immune response. The challenge is when the same inflammation response is mis-directed to target the body - for instance, in rheumatoid arthritis, and other inflammation related auto-immune disorders.
The latest Kurzgesagd video on exercise seemed to imply that (excepting sudden changes in activity level) caloric burn rate is constant regardless of lifestyle, but if you are sedentary, the "excess" calories are burned "unproductively" (e.g. increased inflammation).
So this seems to imply excess calories are a cause of chronic inflammation.
Also, the ketogenic diet has been shown to significantly reduce inflammation, though I'm not sure if that's from reducing carbs, or reducing something else associated with high carb intake.
> caloric burn rate is constant regardless of lifestyle
This is obviously false as stated, extreme athletes consume vastly more calories than sedentary people of their same weight. Phelps was rather famous for a 10,000+ calorie per day diet but even just manual labors need significantly more calories.
I’m assuming there’s some unspecified criteria such as while sleeping?
It's just plain not true. Claims like this coming out in the past few years are based on Herman Pontzer's research in which he measured activity levels and energy expenditure among the Hadza, a forager group in Africa, testing the hypothesis that they'd be using a lot more energy because of how active they are. He found their energy expenditure on average wasn't actually much different than the average for sedentary Americans and developed something called the constrained energy expenditure model. This just postulates that the human body has various ways of compensating in the long term for high activity levels. If less energy is available for basic life processes that are not critical to immediate survival, those process will be modulated downward. Importantly, one of these is inflammation, which is likely why exercise reduces inflammation. At the very extreme end of this, you see things like Marshall Ulrich when he was attempting to break the record for time running across the continental United States seeing things like his hair and nails stopped growing. Female endurance athletes commonly stop having periods. Male endurance athletes often have reduced testosterone production.
But this compensation is nowhere near 100% and it also isn't clear to what extent this is mediated by food availability and possibly the intensity of the activity. The Hadza don't have a lot of food and they're spending all day walking around. Similar studies have been conducted on the Amish, who are doing far harder manual farm labor and have enormous amounts of food, and these studies found much high energy expenditure among the Amish compared to post-industrial sedentary Americans, as well as an average 9% bodyfat for males for whatever that is worth. Similarly, the experiences of endurance athletes with bad health symptoms like amenorrhea and low bone mineral density are limited to people who feel pressure to be as small as possible and don't eat anywhere near enough food. Those who simply eat more don't have the same experiences.
As you stated, we also have quite a bit of clear cut existence proofs that energy expenditure is not simply constant among all people regardless of activity. Pontzer himself has studied some of these extremes to figure out how much energy a human actually can expend. From what I recall, it seemed to be around 3.5 times whatever your base metabolic rate is, at least in the long run. Over short bursts, energy expenditure can be up to 10 times base. The greatest longer duration energy demands he has seen in the field is the Tour de France for men and pregnancy for women, both of which are about equal and seem to represent the limits of what humans can do. Obviously, the people doing these things are eating far more than they would be if they weren't doing those things. Nutrition advice for athletes is nearly the opposite of what it is for the obese and sedentary. Eat sugar like there's no tomorrow. Get as many liquid calories as possible. Avoid high fiber because it'll sit in your gut forever slowing down all other digestion and making you uncomfortable. There's a reason for this.
Two of my favorite podcasts, Stronger by Science and Iron Culture, was in the former case and is in the latter hosted by one of the researchers who works in Herman Pontzer's lab, and he is constantly expressing frustration over how the findings and model get misrepresented by the time they telephone down to pop science communicators and diet influencers. The model simply says that expending X calories per day in exercise will not result in a net difference of X calories expended in total. It'll be some percentage less than 100. But it won't be 0%. Exercise and activity don't make no difference at all.
I'd never heard of this Kurzgesagt thing, but it appears to be a group of animators that make cartoon explainer videos of basically everything? That might be entertaining but is probably not the best way to learn about the frontiers of contemporary nutrition and exercise science.
Glucose and fructose will react non-specifically with proteins in the body, particularly when present in excess. These non-specific reactions are recognized as foreign and/or defective, which triggers inflammation. The apply named RAGE protein is one mediator of this response (https://en.wikipedia.org/wiki/RAGE_(receptor)).
HbA1C results from the non-enzymatic reaction between glucose and hemoglobin. It serves as a measure of your long-term glucose level and is elevated in diabetics.
Low carb diets dramatically reduce this source of inflammation.
That's missing the point. If this technique can result in longer lives for people with both good diets and not, it is a genuinely novel innovation in human life span that can't be replaced with better diet alone.
It could well be that this protein is good for you when you’re young but not that good for you when you are older.
For example, young people might encounter more new infection sources, and thus need a faster/stronger responding immune system. This protein might be evolved for giving you that, with a side effect of having too strong an immune system at older age.
Evolution may not yet have found a solution that turns down its production at later age, or it might have evolved it at some time, but found its benefits do not outweigh the cost of maintaining the necessary control mechanism.
It’s far from a given that having more humans live to old age has evolutionary benefits.
What happens when you eliminate the "good inflammation" in those with bad diets? Then what? There's likely going to be unintended consequences, naturally. My point, eliminating one symptom usually means eventually creating another.
It's not missing the point. The point is that a lot of people live with chronic inflammation caused by poor lifestyle choices and that results in many diseases later in life, including Alzheimer's.
The point is that chronic inflammation is bad. The comment I'm replying to isn't recognizing that it's just saying "oh inflammation is fine because it's a response to injury" which is very much missing the point.
How much of the consequences of a poor life style can be mitigated by simply reducing the chronic inflammation response by the body?
I'd love it if cheap shitty food wasn't bad for me. At the end of the day a calorie is a calorie and many animals handle the stuff that shortens our life with no problem.
Look at it another way, if dogs can't eat chocolate but humans can, is the problem with chocolate or with dogs?
A calorie is certainly not just a calorie. Different foods are metabolized differently and affect the body in different ways, regardless of otherwise equal caloric values. Take fructose, glucose, and ethanol as an example.
The problem there is with dogs, and has nothing to do with calories. Dogs (and many other animals) are simply not able to tolerate chocolate like humans can. Conversely, humans can't tolerate eating rancid meat and cat poop, but dogs can eat those things easily and not get sick. Lots of substances are poisonous to certain species, and non-poisonous to other species.
Also, the reason chocolate is unhealthy isn't because of the cacao plant, it's because of all the added sugar used to make it taste good, since raw cacao (or cocoa, which you get after cooking it) is horribly bitter.
Chronic inflammation is bad. Is chronic inflammation always caused by auto-immune?
Or is it also caused by things like pollutants, poor diet, or other "first world" problems?
I ask because I used to be very concerned with particulate matter (I still am, but I used to too), and it seemed a big problem with that was it triggering inflammation.
It's been a while since I looked into this, but diet is a major factor with inflammation. Sugars, seed oils and grain-fed dairy. (Also if you eat the grains yourself!) Keto lowers it, caloric restriction lowers it (conversely excess calories coupled with sedentary lifestyle increase it), intermittent fasting lowers it.
I forget about exercise, I think it's a case of temporarily increasing it (hours) and then lowering it long-term.
Speaking from personal experience diet plays as much a role as medication in decreasing inflammation. Sugars, gluten, and some* nuts and seeds are indeed pro-inflammatory (many seeds and nuts are anti-inflammatory)
I don't think there's a pattern suggesting that. Many autoimmune diseases are more prevalent in less polluted parts of the world. The strongest links appear to be genetic, in that some diseases (e.g., Sjogren's syndrome) are clearly more common in people of certain geographic descents.
There is no distinction regardless of cause, imo. Stress can epigenetically cause an autoimmune disease, and so can pollution (including smoking), excessive alcohol, processed food diet, sedentariness, etc. Often it is a number of factors that can lead to a chronically overactive immune response.
Antibiotics and sanitation have dramatically changed the fitness landscape and humans haven't accumulated enough generations in the new landscape to adapt genetically.
Natural selection is for reproductive fitness. Before antibiotics, dying after child bearing years didn't have enough effect on fitness to overcome the value of preventing death from infection at younger ages.
Your body attacks substances that appear foreign, whether they're actually foreign or not is another issue.
Human bodies did not evolve for high macro diets, the high levels of sugar (among other molecules) in our diet glycosylate proteins they touch, warping their folding shape and causing inflammation as the body mistake itself for foreign invaders.
Probably a reason why fasting has become so popular, people are walking around with high levels of damage from dense caloric food, a fast allows your body to go through a cycle of catabolism/autophagy. Clearing our the misfolded/damaged proteins lowers inflammation.
I know that some parasites secrete substances that reduce our immune response, for example hook worms. People that have autoimmune diseases of the gut sometimes see a benefit to purposely infecting themselves. I think our current genetic make up was selected by evolution to handle a high parasite load.
Interesting theory. I think it's also still mostly optimized for a pre-agricultural diet.
Keto has been shown to be helpful with a huge number of health issues, and from my understanding humans spent most of the year in ketosis (or all year during the ice ages?).
"Retroactive Why's" are useful because on evolutionary timescales, and it must be if it impacts mice and people, even a very tiny selective pressure causes harmful traits to be selected against.
If as few as 1 in 10,000 reproductions were prevented by a trait then we should expect that trait to be gone in a million years. And our last common ancestor with mice was likely 65 of those past.
Harmful traits can linger if they confer some other benefit. Other's have already worked through this and are rightfully asking, "If this is so harmful it should be have been selected against, what does it do to help us get to successful reproduction in the environment it evolved in?"
okay so explain our short telomeres promoting cancer
what are armchair archeologists going to say, “thats because it enabled strong community ties and the humans with long telomeres didn't value life as strongly” as opposed to being a total freak accident that had nothing to do with anything
Having an immune system. Healing. Exercise causes acute inflammation which signals your body to repair itself. Chronic inflammation is the real problem. And dose, I guess.
I'm not in biology/medicine, but my impression is inflammation is mostly about fighting off infectious diseases. Which, historically, have been a leading killer of mammals.
If current conditions (whether for lab mice, or humans) have removed ~99% of the deadly diseases from the equation - then it's kinda like someone who's heterozygous for sickle cell being stuck in a malaria-free region.
My hunch feels validated. I think it highly depends on area affected because vasoconstriction decreases limphatic throughbout as well as bloodflow. Still highly case-by-case but I think lowering inflammation in load bearing or complex joints like knees or ankles is conducive to nominal operation and therefore healing. (100% rest not recommended, as repair byproducts accumulate and don't clear away, and decreases bloodflow rsults in lower delivery of nutrients, building blocks of tissue, etc.
Inflammation is part of the immune response. It’s generally a good thing if it happens when needed and if it stops when the stimulus is gone. If your immune system is stimulating inflammation for false positives or continuously that is when damage can occur.
Next time you think about consuming a product that claims to boost your immune system, ask yourself if you really want to increase your chances of inflammation or not. they are two sides of the same system.
I just came to ask basically the same question. Why does inflammation exist, what is its purpose, how did it evolve, are there downsides to blocking it?
We have entire classes of drugs including OTC ones whose entire job is just reducing inflammation, its indicated in tons of diseases and conditions, lots of health industry people (and snake oil salesmen) tell me that x and y and z cause it, but I dont really know what it is.
"body's response to an illness, injury or something that doesn't belong in your body (like germs or toxic chemicals)."
If you get a splinter in your finger and it goes red and swollen that's inflammation. It's like the first line general response before things like the immune system kick in.
Limited lifespan is an evolutionarily successful tactic and is a nearly universal trait among living things. Now that we have brains that can do higher order thinking, we can override these and other traits that helped the species survive but are detrimental to individuals.
Perhaps it is not that it is evolutionarily beneficial, but rather a byproduct of other evolutionarily beneficial processes? Such as sending larger amounts of blood to an affected region.
If they released these mice to live in unsanitary wild environment it could turn up they lived shorter/less healthy lives on average because they were less adapted to fight all the pathogens.
Probably has to do with our immune system and microbial threats. You can reduce inflammation using steroids for example but also reduce your immunity as a consequence.
There is virtually no benefit and only downsides to healthy people under 40 supplementing NAD+ via any pathway.
The supplement people will still happily market/sell it to you though, old-school niacin is only 10 cents a day but fancy new NMN/NR is easily $1 a day, they are making a fortune.
Doesn’t niacin lead to prettt severe hot flashes / flushing of the face and extremities? I know someone who was told to take it for cholesterol (I think) and it sounded painful!
How are you tracking the efficacy? Did you measure an actual deficiency in your blood? What effects are you hoping for? If you don't get the desired effects, what will you do?
I always feel a bit of FOMO whenever supplements are being discussed, then again if I bought all the supplements every time I'd have a whole apothecary...
Excerpt from a book I just read, The Renaissance Diet 2.0:
> What about all those cancer studies [about artificial sweeteners] in rats? The first study that initiated this scare was done in the 1970s, and saccharin at high doses was found to cause bladder cancer in rats. Pretty scary, except that in the early 2000s, it was shown that this reaction to saccharin was unique to rats and mechanistically impossible in humans. To illustrate the point, it has also been shown that vitamin C increases tumor growth in rats and mice, but does not seem to have tumor growth effects in humans.
Just sharing as a reminder that studies on animals do not necessarily translate to humans.
> Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications
The "badness" of that number depends on the base rate. The base is getting to regulatory approval by doing exploratory studies on humans tissue (you can't ethically do exploratory studies on human subjects).
If the base rate is 0.5%, then 5% is an order of magnitude improvement and pretty good. If the base rate is 4%, then 5% is pretty bad.
I would suspect that the base rate is far below 0.5%.
But we're not comparing our excitedness about reading results in rats to our excitedness about reading results in human tissue. We're just trying to decide how excited we should be about the rat headlines.
The saccharin research was on both mice and rats, and to this day the jury is still out on manufactured sweeteners and their health impact.
Of course animal models "don't necessarily" translate; a first year med student knows that. Mice are still an excellent model as a step moving closer toward human trials because mice are incredibly similar to us physiologically and genetically, and we have a great deal of understanding about those similarities and differences.
Half the article discusses the challenges involved in trying to move beyond the mouse model to study the phenomenon more.
Do you have a credible source on that? According to the same book:
> The safety of aspartame (a commonly vilified sweetener) is asserted by the independent medical governing bodies of more than 90 countries. It has almost unanimous approval for safety by the top medical and drug safety councils in the world. The FDA has pronounced that aspartame is “one of the most thoroughly tested and studied food additives the agency has ever approved.” The story is much the same for all other major artificial sweeteners, including sucralose, acesulfame potassium, and saccharin. A large amount of calorie-free sweetener can be consumed before an even mild health risk.
The process for such approvals is time and resource intensive. And yet, we have a new & improved artificial sweeteners every few years. Yes, I know the argument... the newest one tastes better. They said the same thing about new Coke.
Seems somewhat odd that something as simple as a sweeter needs to be re-engineered so often.
They are probably re-engineered by different companies so they have a monopoly on that product for the lifetime of the patent. Could also have a different chemical profile in terms of application and taste.
I guess it is like car tires. One variety could service most and it could be made by a single company but every tire manufacture has their own angle.
We don't get a new salt every X years. And that doesn't need to be tested and approved.
* Just a loose example, you can come up with your own additive or whatever.
p.s. For context, I have bad reactions to Aspartame. It took me a couple exposures to figure it out, with the last one nearly landing me in hospital. I certainly understand that nothing engineered is 100% safe. Nonetheless, I have personal experience with one of the "safe" sweeteners.
I'm saying that in order to introduce a new *artificial* sweetener, it is *very* resource intensive.
I'm saying that, if something was maybe showing sing of being "not safe" there's incentive to move on to something new sooner rather than later. That is, if exposure over time to A adds up, then it makes sense to want to move on from A to B sooner rather than later. Else A's flaws are going to be exposed.
Look at statins. The Healthcare Industrial Complex pushed those HARD. And then eventually it was, "Oh wait. These might not be as safe and as positive as we thought..." Then suddenly that push got pushed under the rug as if it never happened.
The irony of it all? We keep getting new & improved artificial sweeteners, and waistlines keep expanding more and more.
> To illustrate the point, it has also been shown that vitamin C increases tumor growth in rats and mice, but does not seem to have tumor growth effects in humans.
Worth noting that regular (non-GMO) mice can synthesize their own vitamin-C without needing it "pre-made" in their diet, unlike [clarification-edit: some but not all] primates (i.e. humans) and sporadic clusters of animals.
In other words, there are already some pretty important differences between how the two species process normal amounts of that nutrient.
It's yet another thing this kind of lay audience doesn't understand about the scientific process. What should you take from studies like this? Nothing. They probably shouldn't even be getting shared to Hacker News. They're conducted because we can't experiment using novel compounds directly on humans until we've shown there is some reason to do so first. Finding an effect on mice is such a reason. This type of research is published for the sake of other researchers, who can now see if the effect is also seen in humans.
Inflammation serves a purpose, blocking it out right gonna have some unknown consequences like when you are supposed to have inflammation but it doesn’t.
My understand was the side effects were mostly stomach related, and that in turn is related to a specific gene. In theory people without the gene were far more likely to tolerate ibuprofen. Excessive alcohol use is also an issue.
Inflammation is an extremely broad term which covers an extremely wide range of chemical responses in the body. You should be _extremely_ skeptical of anything that discusses "inflammation" as a single thing or even an easily understandable set of things. You should also be skeptical of people that link certain diets, nutrients, extracts, etc. to changes in "inflammation".
When people think inflammation they think "inflammation up = oxidative damage". This is the tiniest part of the story. Instead, you should think about the following several things.
1. Every individual component of an inflammatory cascade (=different protein signalling molecules released by cells) has a huge number of different effects. Some component that 'increases inflammation' might cause a certain set of neutrophils to increase oxidative activity in a particular area. That same component, however, might signal to nearby cells to turn on repair genes that close a wound or repair oxidative damage. It might also change the lining of the blood vessels to allow passage of different repair cells or more nutrients to the affected tissue. The bottom line is that if you understand only the "inflammation = oxidative damage" part of this story, you miss the much larger effects this inflammatory cascade is having on the body. In this case, the molecule I am talking about is IL-6; it causes 'inflammation' but it also is the canonical regulator of wound repair in your lungs, skin, and liver. It's a good 'pro-inflammatory' molecule in the right context.
2. Inflammation is not a static measure, it's not a state function. Staying on IL-6 as our example, correct timing of release is critical to cause wound repair in epithelial tissues. If you just see "high IL-6" you can't tell whether that's good or bad. You need to know the local tissue history and where you are in the cycle of damage --> repair.
3. Good neighbors make good fences. You are surrounded (both within and without) by hungry microbes that would love to access the energy your body greedily guards. Your body has two predominant modes of resolving this problem; a) it keeps the microbes out of privileged body spaces (e.g. blood, organs, etc.), b) when they reach those areas it responds to kill them with somewhat indiscriminate oxidative damage. The tradeoff is not "inflammation down --> live in harmony" the tradeoff is "inflammation down --> microbes access privileged body spaces --> inflammation incredibly high to prevent sepsis/bone infection/liver infection/etc". You want certain "inflammatory markers" to be high in the body because they keep nice tight barriers at places where microbes like to leak in (the gut).
4. Studies linking particular nutrients or conditions to "high inflammation" are often very low quality. Even when they are not low quality, it's hard to understand if they are correct in any meaningful sense. Nutrition and chemical exposure are extremely hard to study because you can't do very high quality experiments, you have extremely complex and subtle confounders, and you are operating at spatial scales from individual proteins all the way to the organism level. The chemistry, biology, and physics covered is over such a range that it's really hard to get meaningful mechanistic conclusions. Couple this with the fact that there is a high reward for fad diet/environmental toxicant research (e.g. lots of press, lots of commercial opportunities) and you get a low quality literature.
5. Certain types of chronic inflammation is probably bad, but what is inflammation and what is chronic? You are on solid ground if you stay specific and say something like: "chronic release of canonical 'pro-inflammatory' cytokines IL-4/IL-13 causes atopic dermatitis; contributes to SLE, AK, etc. and blockade of those cytokines with antibodies is an incredibly effective therapy". If you say "sugar causes inflammation and that's bad" it's just much harder to even evaluate what the truth value of that statement is.
>determining the effect of anti-IL-11 drug candidates on longevity in people could be a challenge. A clinical trial examining the impacts on lifespan would be long and expensive...
I wonder if amateur enthusiasts will have a go experimenting on themselves?
Has anyone tried breeding mice for extremely long lifespans? Seems like something that would be fairly simple to implement considering the generational turnaround time of the species.
Not in mice AFAIK, but they've done it with flies which have an even better generational turnaround time (although are less alike to us). Selective breeding of fruit flies at their oldest possible age for breeding, yields longer lifespans in as few as ~12 generations. And the inverse, yields shorter lifespans.
> A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.
What is the evolutionary value of inflammation? It must have a reason for being such a prominent part of life…