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Mice live longer when inflammation-boosting protein is blocked
- michaelteter 2y agoInflammation seems to be a general enemy to health. What is the evolutionary value of inflammation? It must have a reason for being such a prominent part of life…
- takinola 2y agoDumb question: What is inflammation? I know what it sounds like but I realize I am not quite sure what it is.
- tim333 2y ago"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.
- MVissers 2y agoI’d guess it helps short-term survival. Eg: Rest your twisted ankle through pain and inflammation instead of keeping to use it. Even though it increases recovery time, better be on the safe side of decreased usage to avoid further damage. Which is why in modern times RICE speeds up recovery (rest, ice, compression, elevation) in twisted ankles. But we have ratio- which mammels didn’t have for millions of years.
- scns 2y agoIce can do more harm than good: https://drmirkin.com/fitness/why-ice-delays-recovery.html https://drmirkin.com/fitness/why-ice-delays-recovery.html
- datameta 2y agoMy 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.
- netcraft 2y agoI 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.
- calibas 2y agoInflammation actually speeds up healing, at least when things are working right. Edit: To add, much of our medicine treats symptoms, not causes.
- moh_maya 2y agoInflammation 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. [0] https://my.clevelandclinic.org/health/symptoms/21660-inflammation https://my.clevelandclinic.org/health/symptoms/21660-inflamm... [1] https://en.wikipedia.org/wiki/Inflammation?useskin=vector https://en.wikipedia.org/wiki/Inflammation?useskin=vector
- jvanderbot 2y agoChronic 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.
- doe_eyes 2y agoI 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.
- kneel 2y agoYour 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.
- farseer 2y agoProbably 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.
- jb1991 2y agoLong-term steroid use has many many significant side effects as well, like ruining your bones.
- ortusdux 2y ago'If you don't have inflammation, then you'll die': https://www.livescience.com/health/immune-system/if-you-dont-have-inflammation-then-youll-die-how-scientists-are-reprogramming-the-bodys-natural-superpower https://www.livescience.com/health/immune-system/if-you-dont...
- bell-cot 2y agoI'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.
- hooverd 2y agoHaving 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.
- shawnz 2y agoFor this reason anti-inflammatory drugs make exercise less effective: https://www.sciencedaily.com/releases/2017/08/170828125123.htm https://www.sciencedaily.com/releases/2017/08/170828125123.h...
- biomcgary 2y agoAntibiotics 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.
- yieldcrv 2y ago> It must have a reason for being such a prominent part of life… the answer is always "it doesn't kill or sterilize you before you reproduce" I don't understand the point of the retroactive why's. some mutant nutted in a bunch of folks, the end.
- sqeaky 2y ago"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?"
- yieldcrv 2y agookay 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
- ravenstine 2y agoHaving 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
- goda90 2y ago> 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.
- wubrr 2y agoI 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.
- olalonde 2y agoEven 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).
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- ajuc 2y agoIf 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.
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- byteknight 2y agoA super uneducated piece of input for thought: 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.
- thijson 2y agoI 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.
- andai 2y agoInteresting 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?).
- meindnoch 2y agoInflammation is needed so you don't die from infections and injuries.
- epgui 2y agoJust off the top of my head (I am a biochemist), without inflammation you: - cannot heal when injured - cannot fight back against pathogens and die from random infections easily - develop cancer faster and more often
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- DaoVeles 2y agoThanks for the additional context. Generally, the opposite of one bad idea is usually another bad idea. Too much is bad, too little is bad - the middle ground is ideal. For example - Too much water is drowning, doesn't mean we should advocate against water.
- Tagbert 2y agoInflammation 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.
- lern_too_spel 2y agoLimited 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.
- steve1977 2y agoWhat is the evolutionary value of longevity?
- jitbit 2y agoInflammation is a reaction to infection or physical damage. It (1) isolates the damaged tissue from the rest of the body (2) launches countermeasures against most probable threats
- nswest23 2y agoInflammation clearly has a biological purpose - the problem is that the modern world is full of so many things that seem to cause excess inflammation.
- purpleblue 2y agoDo anti-inflammatories like ibuprofen offer the same protections?
- pnw 2y agoAllegedly, yes. Unfortunately the side effects for some people are intolerable. https://www.sciencedaily.com/releases/2014/12/141218141004.htm https://www.sciencedaily.com/releases/2014/12/141218141004.h...
- HumblyTossed 2y ago> Unfortunately the side effects for some people are intolerable. Doesn't it increase one's chances for a heart attack?
- pnw 2y agoMy 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. https://pubmed.ncbi.nlm.nih.gov/27092633/ https://pubmed.ncbi.nlm.nih.gov/27092633/
- ck2 2y agoInflammation also burns up NAD+ in the body as shown by skyrocketing CRP levels (C-Reactive Protein) It's one of the reasons why B3 supplements like NMN and NR (and niacin) are all the rage for "anti-aging" right now to restore NAD+ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146930/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146930/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908681/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908681/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138308/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138308/ https://www.researchgate.net/figure/hs-CRP-levels-in-different-age-groups-Each-bar-represents-the-median-and-95CI-as_fig1_327536451 https://www.researchgate.net/figure/hs-CRP-levels-in-differe...
- qorrect 2y agoAre you taking any NAD+ supplements? I am as of a week ago, just curious if anyone else is.
- bruce343434 2y agoHow 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...
- m3kw9 2y agoInflammation serves a purpose, blocking it out right gonna have some unknown consequences like when you are supposed to have inflammation but it doesn’t.
- tedunangst 2y agoWhat happens if we feed these mice purple tomatoes? https://news.ycombinator.com/item?id=40886385 https://news.ycombinator.com/item?id=40886385
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- olalonde 2y agoExcerpt 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.
- KennyBlanken 2y agoThe 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.
- rgrieselhuber 2y agoOne can just look at the average American and the drink in their hands and pretty easily draw conclusions.
- olalonde 2y agoDo 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.
- GeoAtreides 2y ago> 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. [PDF] https://www.academia.edu/download/87525661/256634.pdf https://www.academia.edu/download/87525661/256634.pdf
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- optimalsolver 2y agoHas 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.
- Rury 2y agoNot 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.
- lawlessone 2y agoI wonder has anyone tried combining all the disparate techniques we have found so far? https://www.nature.com/articles/d41586-023-02224-1 https://www.nature.com/articles/d41586-023-02224-1 There is this other protein too. I always wonder would these combined with things like senolytics etc have a greater effect?
- ed 2y agoYes, in progress (in mice) https://www.levf.org/projects/robust-mouse-rejuvenation-study-1/study-updates https://www.levf.org/projects/robust-mouse-rejuvenation-stud...
- wdwvt1 2y agoInflammation 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.
- darig 2y ago[dead]
- tim333 2y ago>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?