[HN Gopher] Mice live longer when inflammation-boosting protein ...
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       Mice live longer when inflammation-boosting protein is blocked
        
       Author : pseudolus
       Score  : 108 points
       Date   : 2024-07-17 15:52 UTC (7 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | michaelteter wrote:
       | Inflammation 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...
        
         | MVissers wrote:
         | I'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 wrote:
           | Ice can do more harm than good:
           | 
           | https://drmirkin.com/fitness/why-ice-delays-recovery.html
        
             | datameta wrote:
             | 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.
        
         | netcraft wrote:
         | 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.
        
           | calibas wrote:
           | Inflammation actually speeds up healing, at least when things
           | are working right.
           | 
           | Edit: To add, much of our medicine treats symptoms, not
           | causes.
        
         | moh_maya wrote:
         | 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.
         | 
         | [0]
         | https://my.clevelandclinic.org/health/symptoms/21660-inflamm...
         | 
         | [1] https://en.wikipedia.org/wiki/Inflammation?useskin=vector
        
           | jvanderbot wrote:
           | 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.
        
             | doe_eyes wrote:
             | 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.
        
               | jvanderbot wrote:
               | I'm not asking if autoimmune is caused by pollution or
               | development. I'm asking if they both have similar
               | effects.
        
               | datameta wrote:
               | 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.
        
               | datameta wrote:
               | I forgot to add, some have higher genetic predisposition
               | for an autoimmune disorder, and
               | diet/environment/lifestyle can switch those gene sections
               | on.
        
             | andai wrote:
             | 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.
        
               | datameta wrote:
               | 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)
        
           | tempsy wrote:
           | There is a huge difference between inflammation in response
           | to injury and chronic inflammation caused by lifestyle
           | choices like poor diet.
        
             | Teever wrote:
             | 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.
        
               | tempsy wrote:
               | 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.
        
               | Teever wrote:
               | 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?
        
               | BostonFern wrote:
               | 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.
        
               | Teever wrote:
               | How is it that you're making my point in an attempt to
               | refute my point, without seeing that you're making my
               | point for me?
        
               | andai wrote:
               | The question was what are you giving up in exchange? Is
               | this protein's function really just to reduce your
               | quality of life and kill you faster?
        
               | Someone wrote:
               | 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.
        
               | chiefalchemist wrote:
               | 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.
        
           | andai wrote:
           | 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.
        
             | qorrect wrote:
             | This also lines up with something said in the book Lifespan
             | about fasting reducing inflammation.
        
             | biomcgary wrote:
             | 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.
        
             | Retric wrote:
             | > 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?
        
           | jb1991 wrote:
           | Asthma is another example of a terrible problem caused by
           | chronic inflammation.
        
         | kneel wrote:
         | 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.
        
         | farseer wrote:
         | 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.
        
           | jb1991 wrote:
           | Long-term steroid use has many many significant side effects
           | as well, like ruining your bones.
        
         | ortusdux wrote:
         | 'If you don't have inflammation, then you'll die':
         | 
         | https://www.livescience.com/health/immune-system/if-you-dont...
        
         | bell-cot wrote:
         | 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.
        
         | hooverd wrote:
         | 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.
        
           | shawnz wrote:
           | For this reason anti-inflammatory drugs make exercise less
           | effective: https://www.sciencedaily.com/releases/2017/08/1708
           | 28125123.h...
        
         | biomcgary wrote:
         | 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.
        
         | yieldcrv wrote:
         | > 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 wrote:
           | "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 wrote:
             | 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
        
               | sqeaky wrote:
               | > okay so explain our short telomeres promoting cancer
               | 
               | They don't kill us before we procreate. Evolution checks
               | out at childbirth so you get "genetic drift".
        
               | yieldcrv wrote:
               | > the answer is always "it doesn't kill or sterilize you
               | before you reproduce"
               | 
               | QED
        
         | ravenstine wrote:
         | 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
        
           | goda90 wrote:
           | > 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 wrote:
             | 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.
        
               | olalonde wrote:
               | 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).
        
               | wubrr wrote:
               | 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.
        
               | olalonde wrote:
               | > 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.
        
               | wubrr wrote:
               | > 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.
               | 
               | [0]
               | https://www.ctpublic.org/education/2019-05-15/georgetown-
               | stu... [1] https://www.cnbc.com/2019/05/29/study-to-
               | succeed-in-america-...
        
               | olalonde wrote:
               | > 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.
        
               | superturkey650 wrote:
               | 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.
        
               | Retric wrote:
               | > If you only know one thing about someone
               | 
               | 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.
        
               | DaoVeles wrote:
               | Also the Chinese saying that goes "Wealth does not last
               | beyond three generations". There are exceptions to this
               | rule but it is fairly robust.
               | 
               | Part of it is wealth becoming diluted with offspring and
               | secondly being raised in wealth diminishes people value
               | of money until it is too late.
        
               | freen wrote:
               | 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.
        
               | lawlessone wrote:
               | We'd certainly need to change our social system lot.
        
             | Terr_ wrote:
             | > 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.
        
         | ajuc wrote:
         | 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.
        
         | byteknight wrote:
         | A 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 wrote:
         | 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.
        
         | meindnoch wrote:
         | Inflammation is needed so you don't die from infections and
         | injuries.
        
         | epgui wrote:
         | Just 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
        
           | DaoVeles wrote:
           | Thanks 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 wrote:
         | 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.
        
       | purpleblue wrote:
       | Do anti-inflammatories like ibuprofen offer the same protections?
        
         | pnw wrote:
         | Allegedly, yes. Unfortunately the side effects for some people
         | are intolerable.
         | 
         | https://www.sciencedaily.com/releases/2014/12/141218141004.h...
        
           | HumblyTossed wrote:
           | > Unfortunately the side effects for some people are
           | intolerable.
           | 
           | Doesn't it increase one's chances for a heart attack?
        
       | ck2 wrote:
       | Inflammation 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/PMC7908681/
       | 
       | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138308/
       | 
       | https://www.researchgate.net/figure/hs-CRP-levels-in-differe...
        
         | qorrect wrote:
         | Are you taking any NAD+ supplements? I am as of a week ago,
         | just curious if anyone else is.
        
           | bruce343434 wrote:
           | 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...
        
             | inglor_cz wrote:
             | N == 1, but after I started taking NR, my slow descent
             | towards presbyopia (I am 45 now) stopped and reversed
             | itself.
        
           | the__alchemist wrote:
           | I'm taking NMN.
        
         | unsupp0rted wrote:
         | Would a person with normal CRP (measured incidentally a couple
         | times a year) want to take NAD+?
        
           | ck2 wrote:
           | 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.
        
             | voisin wrote:
             | 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!
        
               | simpsond wrote:
               | Yes, too much niacin can make your entire body flush with
               | a burning sensation.
        
               | ck2 wrote:
               | Niacin mega-doses have been used for decades to reduce
               | lipids, triglycerides, etc. and yes when you take 1 gram
               | it will causes a painful flushing.
               | 
               | However to simply raise NAD+ levels you can take as
               | little as 100mg
        
       | m3kw9 wrote:
       | 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.
        
       | tedunangst wrote:
       | What happens if we feed these mice purple tomatoes?
       | https://news.ycombinator.com/item?id=40886385
        
       | olalonde wrote:
       | 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.
        
         | KennyBlanken wrote:
         | 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.
        
           | rgrieselhuber wrote:
           | One can just look at the average American and the drink in
           | their hands and pretty easily draw conclusions.
        
           | olalonde wrote:
           | 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.
        
             | chiefalchemist wrote:
             | 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.
        
               | olalonde wrote:
               | What's odd about it? I'm not sure I understand what you
               | are implying.
        
               | chiefalchemist wrote:
               | 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.
        
               | DaoVeles wrote:
               | 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.
        
               | CamelCaseName wrote:
               | How is it simple? It's the most obvious taste in most
               | foods or drinks it's in, so any minor change is very
               | obvious
        
         | Terr_ wrote:
         | > 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.
        
           | blacksqr wrote:
           | Humans are the only primates that can't make their own
           | vitamin c.
           | 
           | Inability to make vitamin c is a rarity among mammals.
        
             | wcoenen wrote:
             | Humans aren't the only primates with this trait. It's all
             | the Haplorhini.
        
         | hombre_fatal wrote:
         | The translation rate is surprisingly bad.
         | 
         | > Analysis of animal-to-human translation shows that only 5% of
         | animal-tested therapeutic interventions obtain regulatory
         | approval for human applications
         | 
         | https://journals.plos.org/plosbiology/article?id=10.1371/jou...
        
           | abdullahkhalids wrote:
           | 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%.
        
             | amenhotep wrote:
             | 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.
        
         | nonameiguess wrote:
         | 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.
        
       | GeoAtreides wrote:
       | > A traditional Mediterranean dietary pattern, which typically
       | has a high ratio of monounsaturated (MUFA) to saturated (SFA)
       | fats and o-3 to o-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
        
       | optimalsolver wrote:
       | 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.
        
       | lawlessone wrote:
       | I wonder has anyone tried combining all the disparate techniques
       | we have found so far?
       | 
       | 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?
        
       | wdwvt1 wrote:
       | 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.
        
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