Mice live longer when inflammation-boosting protein is blocked

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…

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...

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.

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.

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?

Do anti-inflammatories like ibuprofen offer the same protections?

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.

> 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

What happens if we feed these mice purple tomatoes? https://news.ycombinator.com/item?id=40886385