13 ms·

The amyloid, T3D, and viral hypotheses still don't explain why cholesterol, obesity, air pollution, lack of sleep, and sedentary liftestyle positively correlate

The amyloid, T3D, and viral hypotheses still don't explain why cholesterol, obesity, air pollution, lack of sleep, and sedentary liftestyle positively correlate with Alzheimer's and high caffeine intake and regular exercise negatively correlate with it.

subcosmos 8y ago
They do, if you consider the recent findings that many viruses have evolved to exploit our colesterol synthesis and transport machinery to spread, it becomes clear that many diseases of aging may have a viral cause : https://medium.com/@InfinoMe/senescence-links-between-heart-disease-genomics-and-aging-fa78bde773da https://medium.com/@InfinoMe/senescence-links-between-heart-... Rhinovirus, the cause of the common cold, binds to vLDL receptors. vLDL incidentally being the primary risk factor for cardiovascular disease https://www.ncbi.nlm.nih.gov/pubmed/12857919 https://www.ncbi.nlm.nih.gov/pubmed/12857919 Influenza requires the cholesterol transport system to bud and spread http://news.mit.edu/2017/cholesterol-helps-flu-virus-escape-through-host-cell-membrane-1120 http://news.mit.edu/2017/cholesterol-helps-flu-virus-escape-... Hepatitis C virus relies on APO-E, our favorite alzheimers gene, to flourish, and APO-E genotype predicts if you will get liver cancer from Hep-B https://goo.gl/images/Hev5ev https://goo.gl/images/Hev5ev T2D, CVD, and obesity, being characterized by hypercholesterolemia and mitochondrial dysfunction, are illnesses that are supportive of viral infections. They also promote AGE formation, which activates the innate immune system through a variety of RAGE receptors, Galectin-3 being potentially a central axis as it is also part of the senescent phenotype.
- trendia 8y ago
  In the context of the infectious disease hypothesis, do you know why caffeine / coffee would be associated with lower incidence of Alzheimer's? (It reduces amyloid-beta levels, but if plaques are not the cause of Alzheimer's then this shouldn't provide any protective benefit)
  - subcosmos 8y ago
    It's ongoing work for me. Lately I've been digging through a lot of gene expression datasets to try and figure out which genes are the most overexpressed in aging tissues. I then use bioinformatics tools like clue.io to figure out which OTHER genes regulate them, and also possible drugs. There are a number of pathways that seem to be downregulated by purigenic receptors, many of which are sensitive to adenosine. Caffeine blocks adenosine receptors and blocks signaling. What could be happening here is suppressing inflammation, since evidently purine nucleotides activate some immune cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568887/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568887/
    - nonbel 8y ago
      Its not difficult to come up with mechanisms like that, not even difficult to come up with the idea and then get some evidence consistent with it. The key is to make sure everything works out quantitatively: https://www.ncbi.nlm.nih.gov/pubmed/12242150 https://www.ncbi.nlm.nih.gov/pubmed/12242150
    - ishwarn 8y ago
      So this theory holds for caffeine, not specifically coffee? I'm not sure why, but I was under the impression that it was specifically coffee that could be tied to lower incidence of Alzheimers.
    - mrfusion 8y ago
      Can’t it be as simple as caffeine boosts your metabolism and mutes blood sugar spikes?
- inciampati 8y ago
  You tied together a lot of threads that I've been loosely aware of here. Nice post. I hope we a have the chance to elucidate what of these links is relevant and actionable.
  - subcosmos 8y ago
    I'm very confident in the future. What a time it is to be alive.

subcosmos 8y ago

They do, if you consider the recent findings that many viruses have evolved to exploit our colesterol synthesis and transport machinery to spread, it becomes clear that many diseases of aging may have a viral cause : https://medium.com/@InfinoMe/senescence-links-between-heart-disease-genomics-and-aging-fa78bde773da https://medium.com/@InfinoMe/senescence-links-between-heart-... Rhinovirus, the cause of the common cold, binds to vLDL receptors. vLDL incidentally being the primary risk factor for cardiovascular disease https://www.ncbi.nlm.nih.gov/pubmed/12857919 https://www.ncbi.nlm.nih.gov/pubmed/12857919 Influenza requires the cholesterol transport system to bud and spread http://news.mit.edu/2017/cholesterol-helps-flu-virus-escape-through-host-cell-membrane-1120 http://news.mit.edu/2017/cholesterol-helps-flu-virus-escape-... Hepatitis C virus relies on APO-E, our favorite alzheimers gene, to flourish, and APO-E genotype predicts if you will get liver cancer from Hep-B https://goo.gl/images/Hev5ev https://goo.gl/images/Hev5ev T2D, CVD, and obesity, being characterized by hypercholesterolemia and mitochondrial dysfunction, are illnesses that are supportive of viral infections. They also promote AGE formation, which activates the innate immune system through a variety of RAGE receptors, Galectin-3 being potentially a central axis as it is also part of the senescent phenotype.

trendia 8y ago
In the context of the infectious disease hypothesis, do you know why caffeine / coffee would be associated with lower incidence of Alzheimer's? (It reduces amyloid-beta levels, but if plaques are not the cause of Alzheimer's then this shouldn't provide any protective benefit)
- subcosmos 8y ago
  It's ongoing work for me. Lately I've been digging through a lot of gene expression datasets to try and figure out which genes are the most overexpressed in aging tissues. I then use bioinformatics tools like clue.io to figure out which OTHER genes regulate them, and also possible drugs. There are a number of pathways that seem to be downregulated by purigenic receptors, many of which are sensitive to adenosine. Caffeine blocks adenosine receptors and blocks signaling. What could be happening here is suppressing inflammation, since evidently purine nucleotides activate some immune cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568887/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568887/
  - nonbel 8y ago
    Its not difficult to come up with mechanisms like that, not even difficult to come up with the idea and then get some evidence consistent with it. The key is to make sure everything works out quantitatively: https://www.ncbi.nlm.nih.gov/pubmed/12242150 https://www.ncbi.nlm.nih.gov/pubmed/12242150
  - ishwarn 8y ago
    So this theory holds for caffeine, not specifically coffee? I'm not sure why, but I was under the impression that it was specifically coffee that could be tied to lower incidence of Alzheimers.
  - mrfusion 8y ago
    Can’t it be as simple as caffeine boosts your metabolism and mutes blood sugar spikes?
inciampati 8y ago
You tied together a lot of threads that I've been loosely aware of here. Nice post. I hope we a have the chance to elucidate what of these links is relevant and actionable.
- subcosmos 8y ago
  I'm very confident in the future. What a time it is to be alive.