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Herpes Simplex Infection Correlates with Amyloid Burden in the Aging Brain


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#1 reason

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Posted 15 April 2024 - 10:11 AM


There is a continuing debate over the degree to which Alzheimer's is driven by persistent infection in brain tissue, such as by varieties of herpesvirus. Amyloid-β is an antimicrobial peptide, a part of the innate immune response, and one could argue that persistently raised expression of amyloid-β will increase misfolding and generation of the aggregates that drive pathology in the early stages of Alzheimer's disease, at least under the amyloid cascade hypothesis. The data is not all convincing, however, which suggests that perhaps there are other factors involved - that multiple viruses interact in some people, for example, or a pathological interaction between viral infection and some other aspect of brain aging only occurs in some people. It remains to be seen as to where this line of research will lead, but even now it seems a good cost-benefit decision to be using antiviral drugs in later life.

Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of Alzheimer's disease (AD), possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lacking in normal aging. To shed light into this question, serum anti-HSV IgG levels were correlated with measures of Aβ deposits and blood markers of neurodegeneration in cognitively normal older adults. Additionally, we investigated whether associations between anti-HSV IgG and AD markers were more evident in APOE4 carriers.

We showed that increased anti-HSV IgG levels are associated with higher Aβ load in fronto-temporal regions of cognitively normal older adults. Remarkably, these cortical regions exhibited abnormal patterns of resting state-functional connectivity (rs-FC) only in those individuals showing the highest levels of anti-HSV IgG. We further found that positive relationships between anti-HSV IgG levels and Aβ load, particularly in the anterior cingulate cortex, are moderated by the APOE4 genotype, the strongest genetic risk factor for AD. Importantly, anti-HSV IgG levels were unrelated to either subclinical cognitive deficits or to blood markers of neurodegeneration.

These results suggest that HSV infection is selectively related to cortical Aβ deposition in normal aging, supporting the inclusion of cognitively normal older adults in prospective trials of antimicrobial therapy aimed at decreasing the AD risk in the aging population.

Link: https://doi.org/10.1...195-024-01437-4


View the full article at FightAging

#2 timedilation

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Posted 15 April 2024 - 03:09 PM

Yeah, I think the evidence is pretty conclusive at this point that latent viruses (HSV, EBV, CMV, etc.) are devastating for longevity, and we desperately need therapies that can eliminate them permanently.  What is the status of DRACO these days?  Are there any other promising areas of antiviral research going on?


Edited by timedilation, 15 April 2024 - 03:09 PM.


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#3 Mind

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Posted 16 April 2024 - 10:11 PM

Considering that our knowledge of viral ecology is woefully rudimentary, and the world is completely covered with them (inside and out), I am unsure if we should take a scorched-earth approach, but maybe a very selective and "surgical" approach.

 

 

 

Supercentenarians have been exposed to the same viruses as everyone else and still out live everyone else. Maybe it would be better to focus on enhancing and turbo-charging the immune system.



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#4 timedilation

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Posted 16 April 2024 - 11:27 PM

Supercentenarians have been exposed to the same viruses as everyone else and still out live everyone else. 

I could not disagree with this idea more.  Supercentenarians have also been exposed to leaded gasoline, leaded paint, glyphosate, mercury antiseptics, and dozens of other poisons humanity has unleashed.  That doesn't mean we should just learn to live with any of them.  Part of their longevity very likely lies in their superior ability to adapt to or avoid these types of insults.  Moreover, it is very plausible that supercentenarians could live even longer if these pathologies did not exist.  Any such toxin or pathogen eradicated yields a longevity benefit to all of humanity.  

 

Plus, this doesn't have to be either/or.  I would gladly welcome the arrival of gene therapies based on protective SNPs found in supercentenarians as well.

 

 

maybe a very selective and "surgical" approach

This I agree with.  My point was that we should target known harmful viruses like HSV/EBV, not simply remove every segment of viral origin in our DNA.


Edited by timedilation, 16 April 2024 - 11:39 PM.





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