17 ms·

Study Reveals Immune Driver of Brain Aging

232 points by oedmarap 6y ago

Wowfunhappy 6y ago
^ This probably needs "in mice" integrated into the title somehow—but it's still a cool article.
- gnicholas 6y ago
  Looks like they've done this with mice and with cultured human cells. > If their findings in old mice and in human cell cultures apply to actual humans, they could presage the pharmaceutically managed recovery of older people’s mental abilities.
wizzwizz4 6y ago
Original paper: https://doi.org/10.1038/s41586-020-03160-0 https://doi.org/10.1038/s41586-020-03160-0
- swader999 6y ago
  From the paper: In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. - I wonder if fasting helps reduce this.
treeman79 6y ago
Brain fog is common with autoimmune conditions. Often one of the first symptoms that cause people to seek a diagnosis. Have Sjogrens. Cognitive decline is a real issue for me. Treatment and lifestyle changes make a huge difference. Basically controlling inflammation becomes your life. Or you won’t have much of one.
- MetalGuru 6y ago
  What have been the most effective lifestyle changes you've made? And how long did it take you before noticing their effects? Hope they continue working for you!
  - treeman79 6y ago
    Support groups are best. Knowing your not alone. A safe place to ask questions. Facebook groups are biggest and best. Reddit has a lot too. Various podcasts and foundations. From these you start seeing patterns in what works for people, how to find doctors. For me. In order of improvement. Prescription: plaqunial. Blood thinners. Avoiding flare triggers, Sun, heat, most foods. Diet is huge. Autoimmune protocol diet is best for me. Similar to keto, etc. Personally I’ll eat a lot of sweet potatoes when I need relief. Safest food I have found. Supplement: Vit D, magnesium, Vit E, fish oil, B complex, CQ-10 turmeric. Autoimmune often means a lot of secondary conditions, or autoimmune is the secondary. Increased cranial pressure is somewhat common with Sjogrens for example. High pressure is brutal on the mind and body. Went from bed ridden in horrific agony all day to kayaking or equivalent every weekend.
    - datameta 6y ago
      It makes me so happy to read this! I too have had a drastic transformation in terms of life quality. I second the Anti-inflammatory diet and exercise (even just walking contributes greatly). I echo the supplement suggestions and also recommend glucosamine+chondroitin (which happens to lower all-cause mortality significantly). Red meats (high omega 6 content), deeply fried foods, gluten (plenty of grain alternatives to wheat and corn), uncultured dairy (cheese seems ok, plenty of alt-milks out there), and sugar not from fruit can trigger inflammation for me. I might describe my diet as vegan+eggs+fish (ovo-pescaterian?) There is a wealth of information online to tailor one's diet. Honestly - this is a diet that everyone can benefit from health wise.
      - dualthro 6y ago
        I'm jealous that you can eat grains! Any kind sets me off unfortunately. And yeah it took me a while to realize but any kind of fried food is bad for me. So even eating coconut tortilla chips sets me off, despite the fact that they contain no grain. I am hopeful that in the future, more paleo / autoimmune paleo targeting brands come out. There was already a pleasantly surprising amount of brands catering to this, last time I was at a whole foods. For those who can't tolerate dairy, or any kinds of nuts or seeds or grains, one kind of food that you might enjoy is coconut yogurt. Not cheap but it helps to break some of the dietary monotony.
deleted 6y ago
[deleted]
nostromo 6y ago
This reminds me of Rapamycin, an immunosuppressant that also makes most animals live much longer — something longevity hackers are experimenting with now.
arnonejoe 6y ago
Originally reported in Nature on Jan 20. https://www.nature.com/articles/d41586-021-00063-6 https://www.nature.com/articles/d41586-021-00063-6
helge9210 6y ago
...in mice ©
sradman 6y ago
The paper Restoring metabolism of myeloid cells reverses cognitive decline in ageing [1]: > Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions. [1] https://www.nature.com/articles/s41586-020-03160-0 https://www.nature.com/articles/s41586-020-03160-0
nickelcitymario 6y ago
Because an awful lot of this goes over my head, can anyone tell me if these findings could potentially apply to all auto-immune diseases? Or just those related to the brain?
- theflyinghorse 6y ago
  > an awful lot I am lucky to understand 10% maybe. I wish there was a scientific journal which would dumb it down for the layman.
magoghm 6y ago
Some day we are going to discover how to apply all research results like this one, and we'll end up with the healthiest mice ever :)
- kharak 6y ago
  I started to hope that someone is going to do exactly that. What if we really try to create the most healthy, long living mice? Could we do it? How much healthier could it get? If the answer "several orders of magnitude", the risk averse zeitgeist towards human medicine might change.
retzkek 6y ago
A study from 2014 [^1] indicated that prolonged fasting (2-5 days) caused the regeneration of immune cells and "reversed age-dependent myeloid-bias in mice". I don't have the knowledge to fully understand the implications of this, but it seems it supports reports that fasting has positive effects on aging-related brain degeneration. I fast semi-regularly (I'm just finishing up a four-day fast), and it amazes me how often we by default reach for something (e.g. pills) to put into our bodies to solve or improve something, when sometimes the answer is to _not_ put something (i.e. food) in it (at least for a little bit). It's also a great exercise in self-control and discipline. ^1: https://pubmed.ncbi.nlm.nih.gov/24905167/ https://pubmed.ncbi.nlm.nih.gov/24905167/
- pps 6y ago
  There is a great book on all kind of benefits of fasting (it provides also ideas for diet on periods of normal eating): The Longevity Diet by Valter Longo (legitimate scientist).
  - agumonkey 6y ago
    He was quoted not long ago for his segment with Rhonda Patrick about diet.
- deleted 6y ago
  [deleted]
xwdv 6y ago
Lately I haven’t really been too convinced about the benefits of fasting. While fasting is probably good, exercising regularly and putting a consistent stream of good nutrients into your body is still probably better at preventing all kinds of aging. Fasting is just more accessible to those who do not have access to steady source of good nutrition, and it takes no real effort beyond not eating.
- pps 6y ago
  It's all about autophagy. You can trigger it with diet, but it's way easier to just do fasting 7 days every 3 months or 3 days every month. (obviously exercise and good diet is also important) https://www.healthline.com/health/autophagy https://www.healthline.com/health/autophagy
WalterBright 6y ago
I've been reading "The End of Alzheimers" which implicates inflammation as one of the 36 (!) causes of Alzheimers.
louis8799 6y ago
I had brain fog since college and I am now 31, I started running 1 year ago, and I am now running 50+ km per week. Haven't had even one brain fog ever since, feel like iron man everyday.
- DoreenMichele 6y ago
  Yeah, movement helps clear lymph which is how the body takes out the trash.
- brational 6y ago
  article itself mentions issue of hoarding glucose instead of using it. elevated HR via exercise basically forces glucose to be used so. not surprising at all.
mickelsen 6y ago
I just got out of a rut that had me a year down, wellbutrin helped a bit but couldn't go on longer than a few months because of the resulting insomnia, and while it didn't really lift the brain fog, it worked very well with the panic attacks I was having from ADHD meds or coffee (after years of using them, lately with diminishing returns) When I went back to the basics done right, and stopped doing experiments on myself like fasting or energy drinks at certain times, everything slowly went back into place, it only took about 3 weeks and compounding effects after a few months. Basically, consistency was key: Start the day with aminoacids + b-complex, water soluble vitamins on empty stomach work better. Then a protein breakfast, like 4 eggs and some greens. Eggs are a good source of choline. Only now I'd pop a vyvanse, less aggressive/spiky effect but also less anxiety and lasts longer on a neutral stomach. Replace coffee with matcha. Has the caffeine + theanine for relaxation, and slower release. Happier gut as well. Extended lunch break: small meal but time for a walk with my gf, light exercise, call a friend or errands, then slowly transition back to work and finish the day. For dinner get your Omegas and Vitamin E (lowers inflammation), fat soluble vitamins do better on a full stomach. Before bed maybe some Melatonin and Magnesium. About supplements for brain fog, maybe try some extra B1 (Thiamine, there's also Sulbuthiamine), Ginseng. Get tested for anemia, even if the basic blood panel looks OK, just get a video doctor to hand you out an exam order for the usual suspects like ferritin, serum iron, plasma electrolytes, b6/b12, d, c, folate. If it's low but not anemia-level low, you could supplement, it seems pretty common with iron. Low Vitamin D won't really change with those 800 IU pills, get those salts that have 50.000 IU once per week then retest after a month.
aamygrahams 6y ago
I was around 58 when my thumb started giving me problems. As time passed i had other symptoms; hand tremors, restless sleep, muscle weakness, cognitive decline, voice spasm, stiff achy right arm and ankle. At 60 i was diagnose of PARKINSONS DISEASE, i was on Carbidopa and Pramipexole for two years, they helped alot but not for long. As the disease progressed my symptoms worsened, with my neurologist guidance i started on natural alternative PARKINSONS DISEASE treatment from M.H.C. (Mayaka Natural Clinic), the treatment worked very effectively, my severe symptoms simply vanished, i feel better now than I have ever felt and i can feel my strength again. Visit ww w. mayakanaturalclinic. c om. c om. My neurologist was very open when looking at alternative medicines and procedures, this alternative parkinson disease treatment is a breakthrough.
aamygrahams 6y ago
After my Parkinson's Disease diagnosis, my primary care provider introduced me to Mayaka Natural Clinic and their PD Formula protocol, the herbal treatment has made a tremendous difference for me. My symptoms including numbness and muscle weakness all disappeared after the treatment plan! Their website is w w w. mayakanaturalclinic. c o m

232 points by oedmarap 6y ago

Wowfunhappy 6y ago

^ This probably needs "in mice" integrated into the title somehow—but it's still a cool article.

gnicholas 6y ago
Looks like they've done this with mice and with cultured human cells. > If their findings in old mice and in human cell cultures apply to actual humans, they could presage the pharmaceutically managed recovery of older people’s mental abilities.

wizzwizz4 6y ago

Original paper: https://doi.org/10.1038/s41586-020-03160-0 https://doi.org/10.1038/s41586-020-03160-0

swader999 6y ago
From the paper: In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. - I wonder if fasting helps reduce this.

treeman79 6y ago

Brain fog is common with autoimmune conditions. Often one of the first symptoms that cause people to seek a diagnosis. Have Sjogrens. Cognitive decline is a real issue for me. Treatment and lifestyle changes make a huge difference. Basically controlling inflammation becomes your life. Or you won’t have much of one.

MetalGuru 6y ago
What have been the most effective lifestyle changes you've made? And how long did it take you before noticing their effects? Hope they continue working for you!
- treeman79 6y ago
  Support groups are best. Knowing your not alone. A safe place to ask questions. Facebook groups are biggest and best. Reddit has a lot too. Various podcasts and foundations. From these you start seeing patterns in what works for people, how to find doctors. For me. In order of improvement. Prescription: plaqunial. Blood thinners. Avoiding flare triggers, Sun, heat, most foods. Diet is huge. Autoimmune protocol diet is best for me. Similar to keto, etc. Personally I’ll eat a lot of sweet potatoes when I need relief. Safest food I have found. Supplement: Vit D, magnesium, Vit E, fish oil, B complex, CQ-10 turmeric. Autoimmune often means a lot of secondary conditions, or autoimmune is the secondary. Increased cranial pressure is somewhat common with Sjogrens for example. High pressure is brutal on the mind and body. Went from bed ridden in horrific agony all day to kayaking or equivalent every weekend.
  - datameta 6y ago
    It makes me so happy to read this! I too have had a drastic transformation in terms of life quality. I second the Anti-inflammatory diet and exercise (even just walking contributes greatly). I echo the supplement suggestions and also recommend glucosamine+chondroitin (which happens to lower all-cause mortality significantly). Red meats (high omega 6 content), deeply fried foods, gluten (plenty of grain alternatives to wheat and corn), uncultured dairy (cheese seems ok, plenty of alt-milks out there), and sugar not from fruit can trigger inflammation for me. I might describe my diet as vegan+eggs+fish (ovo-pescaterian?) There is a wealth of information online to tailor one's diet. Honestly - this is a diet that everyone can benefit from health wise.
    - dualthro 6y ago
      I'm jealous that you can eat grains! Any kind sets me off unfortunately. And yeah it took me a while to realize but any kind of fried food is bad for me. So even eating coconut tortilla chips sets me off, despite the fact that they contain no grain. I am hopeful that in the future, more paleo / autoimmune paleo targeting brands come out. There was already a pleasantly surprising amount of brands catering to this, last time I was at a whole foods. For those who can't tolerate dairy, or any kinds of nuts or seeds or grains, one kind of food that you might enjoy is coconut yogurt. Not cheap but it helps to break some of the dietary monotony.

deleted 6y ago

[deleted]

nostromo 6y ago

This reminds me of Rapamycin, an immunosuppressant that also makes most animals live much longer — something longevity hackers are experimenting with now.

arnonejoe 6y ago

Originally reported in Nature on Jan 20. https://www.nature.com/articles/d41586-021-00063-6 https://www.nature.com/articles/d41586-021-00063-6

helge9210 6y ago

...in mice ©

sradman 6y ago

The paper Restoring metabolism of myeloid cells reverses cognitive decline in ageing [1]: > Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions. [1] https://www.nature.com/articles/s41586-020-03160-0 https://www.nature.com/articles/s41586-020-03160-0

nickelcitymario 6y ago

Because an awful lot of this goes over my head, can anyone tell me if these findings could potentially apply to all auto-immune diseases? Or just those related to the brain?

theflyinghorse 6y ago
> an awful lot I am lucky to understand 10% maybe. I wish there was a scientific journal which would dumb it down for the layman.

magoghm 6y ago

Some day we are going to discover how to apply all research results like this one, and we'll end up with the healthiest mice ever :)

kharak 6y ago
I started to hope that someone is going to do exactly that. What if we really try to create the most healthy, long living mice? Could we do it? How much healthier could it get? If the answer "several orders of magnitude", the risk averse zeitgeist towards human medicine might change.

retzkek 6y ago

A study from 2014 [^1] indicated that prolonged fasting (2-5 days) caused the regeneration of immune cells and "reversed age-dependent myeloid-bias in mice". I don't have the knowledge to fully understand the implications of this, but it seems it supports reports that fasting has positive effects on aging-related brain degeneration. I fast semi-regularly (I'm just finishing up a four-day fast), and it amazes me how often we by default reach for something (e.g. pills) to put into our bodies to solve or improve something, when sometimes the answer is to _not_ put something (i.e. food) in it (at least for a little bit). It's also a great exercise in self-control and discipline. ^1: https://pubmed.ncbi.nlm.nih.gov/24905167/ https://pubmed.ncbi.nlm.nih.gov/24905167/

pps 6y ago
There is a great book on all kind of benefits of fasting (it provides also ideas for diet on periods of normal eating): The Longevity Diet by Valter Longo (legitimate scientist).
- agumonkey 6y ago
  He was quoted not long ago for his segment with Rhonda Patrick about diet.
deleted 6y ago
[deleted]

xwdv 6y ago

Lately I haven’t really been too convinced about the benefits of fasting. While fasting is probably good, exercising regularly and putting a consistent stream of good nutrients into your body is still probably better at preventing all kinds of aging. Fasting is just more accessible to those who do not have access to steady source of good nutrition, and it takes no real effort beyond not eating.

pps 6y ago
It's all about autophagy. You can trigger it with diet, but it's way easier to just do fasting 7 days every 3 months or 3 days every month. (obviously exercise and good diet is also important) https://www.healthline.com/health/autophagy https://www.healthline.com/health/autophagy

WalterBright 6y ago

I've been reading "The End of Alzheimers" which implicates inflammation as one of the 36 (!) causes of Alzheimers.

louis8799 6y ago

I had brain fog since college and I am now 31, I started running 1 year ago, and I am now running 50+ km per week. Haven't had even one brain fog ever since, feel like iron man everyday.

DoreenMichele 6y ago
Yeah, movement helps clear lymph which is how the body takes out the trash.
brational 6y ago
article itself mentions issue of hoarding glucose instead of using it. elevated HR via exercise basically forces glucose to be used so. not surprising at all.

mickelsen 6y ago

I just got out of a rut that had me a year down, wellbutrin helped a bit but couldn't go on longer than a few months because of the resulting insomnia, and while it didn't really lift the brain fog, it worked very well with the panic attacks I was having from ADHD meds or coffee (after years of using them, lately with diminishing returns) When I went back to the basics done right, and stopped doing experiments on myself like fasting or energy drinks at certain times, everything slowly went back into place, it only took about 3 weeks and compounding effects after a few months. Basically, consistency was key: Start the day with aminoacids + b-complex, water soluble vitamins on empty stomach work better. Then a protein breakfast, like 4 eggs and some greens. Eggs are a good source of choline. Only now I'd pop a vyvanse, less aggressive/spiky effect but also less anxiety and lasts longer on a neutral stomach. Replace coffee with matcha. Has the caffeine + theanine for relaxation, and slower release. Happier gut as well. Extended lunch break: small meal but time for a walk with my gf, light exercise, call a friend or errands, then slowly transition back to work and finish the day. For dinner get your Omegas and Vitamin E (lowers inflammation), fat soluble vitamins do better on a full stomach. Before bed maybe some Melatonin and Magnesium. About supplements for brain fog, maybe try some extra B1 (Thiamine, there's also Sulbuthiamine), Ginseng. Get tested for anemia, even if the basic blood panel looks OK, just get a video doctor to hand you out an exam order for the usual suspects like ferritin, serum iron, plasma electrolytes, b6/b12, d, c, folate. If it's low but not anemia-level low, you could supplement, it seems pretty common with iron. Low Vitamin D won't really change with those 800 IU pills, get those salts that have 50.000 IU once per week then retest after a month.

aamygrahams 6y ago

I was around 58 when my thumb started giving me problems. As time passed i had other symptoms; hand tremors, restless sleep, muscle weakness, cognitive decline, voice spasm, stiff achy right arm and ankle. At 60 i was diagnose of PARKINSONS DISEASE, i was on Carbidopa and Pramipexole for two years, they helped alot but not for long. As the disease progressed my symptoms worsened, with my neurologist guidance i started on natural alternative PARKINSONS DISEASE treatment from M.H.C. (Mayaka Natural Clinic), the treatment worked very effectively, my severe symptoms simply vanished, i feel better now than I have ever felt and i can feel my strength again. Visit ww w. mayakanaturalclinic. c om. c om. My neurologist was very open when looking at alternative medicines and procedures, this alternative parkinson disease treatment is a breakthrough.

aamygrahams 6y ago

After my Parkinson's Disease diagnosis, my primary care provider introduced me to Mayaka Natural Clinic and their PD Formula protocol, the herbal treatment has made a tremendous difference for me. My symptoms including numbness and muscle weakness all disappeared after the treatment plan! Their website is w w w. mayakanaturalclinic. c o m