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I found this interesting. University of Pittsburgh (yeah!) researchers have found [1] (press release) that cognition tends to decline much more rapidly in elderly folks who test positive for chronic, seemingly harmless viral infections, such as cytomegalovirus, toxoplasma gondii (the virus that makes rats love cats, and humans take risks!), and various herpes simplex viruses. The lead author said:


“It’s possible that these viruses, which can linger in the body long after acute infection, are triggering some neurotoxic effects.”


The smart folks over at Fight Aging! observe:


A good deal of evidence from past years supports the theory that CMV accelerates immune system aging, causing the immune system to devote ever more of its limited capacity to uselessly fighting CMV rather than productively carrying out its other tasks. Our immune response is incapable of clearing CMV from the body, and the virus lingers to return in force again and again regardless of the effort devoted to battle it.


Chronic infections with these three viruses is surprisingly common.  T. gondii infection rates are around 22% of the general population. And between 50 and 80% of people are infected with cytomegalovirus by age 40!


I wonder if chronic elevation of WBC, as a sign of chronic infection, is associated with accelerated cognitive decline...  I suspect it probably is. For CRers whose WBC count remains unusually high, it might be worth getting tested for chronic viral infections, including the three listed above.





[1] Alzheimer Dis Assoc Disord. 2015 Dec 24. [Epub ahead of print]

Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a
Population-based, Aging Cohort.

Nimgaonkar VL(1), Yolken RH, Wang T, Chung-Chou HC, McClain L, McDade E, Snitz
BE, Ganguli M.

Author information:
(1)Departments of *Psychiatry ∥Medicine ¶Neurology, University of Pittsburgh
School of Medicine Departments of †Human Genetics §Biostatistics #Epidemiology,
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
‡Department of Pediatrics, Stanley Division of Neurovirology, Johns Hopkins
University School of Medicine, Baltimore, MD.

BACKGROUND: Numerous cross-sectional studies have related exposure to neurotropic
infectious agents with cognitive dysfunction in older adults, however, the
temporal sequence is uncertain.

METHODS: In a representative, well-characterized, population-based aging cohort,
we determined whether the temporal trajectories of multiple cognitive domains are
associated with exposure to cytomegalovirus (CMV), Herpes Simplex virus, type 1
(HSV-1), Herpes Simplex virus, type 2 (HSV-2), or Toxoplasma gondii (TOX).
Complex attention, executive functions, memory, language, and visuospatial
function were assessed annually for 5 years among consenting individuals. Study
entry IgG antibody titers indexing exposure to each infectious agent were
examined in relation to slopes of subsequent temporal cognitive decline using
multiple linear regressions adjusted for potential confounders.
RESULTS: The IgG levels for HSV-2 were significantly associated with baseline
cognitive domain scores (N=1022 participants). Further, the IgG levels for HSV-2,
TOX, and CMV, but not HSV-1 were significantly associated with greater temporal
cognitive decline that varied by type of infection.
CONCLUSIONS: Exposure to CMV, HSV-2, or TOX is associated with cognitive
deterioration in older individuals, independent of general age-related variables.
An increased understanding of the role of infectious agents in cognitive decline
may lead to new methods for its prevention and treatment.

PMID: 26710257

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Thanks, Dean,


IgG is the best test for herpes virus, CMV.  My IgG was mid-range initially, but with increasing CR decreased.  You should know if you have herpes virus type 2, genital herpes.


TABLE 1. Associations of Baseline Cognitive Domain Composite and MMSE Scores With Seropositivity for Antibodies to Infectious
Infectious Agents CMV HSV-1 HSV-2 TOX
Proportion of individuals exposed* (%) 83 78 10 48
Cognitive domains [beta (P)]w
Attention 0.0754 (NS) 0.0613 (NS) 0.1745 (0.017) 0.0046 (NS)
Executive function 0.0314 (NS) 0.0193 (NS) 0.2017 (0.003) 0.0766 (NS)
Memory 0.0217 (NS) 0.0936 (NS) 0.2264 (0.002) 0.0706 (NS)
Language 0.0161 (NS) 0.0575 (NS) 0.3046 (< 0.001) 0.0465 (NS)
Visuospatial function 0.0327 (NS ) 0.0147 (NS) 0.4153 (< 0.001) 0.1033 (NS)
MMSE 0.0809 (NS) 0.0852 (NS) 0.6047 (0.006) 0.0816 (NS)
   *The proportion of individuals exposed to each infections agent was estimated using predetermined cutoffs in antibody levels, see the Methods section.
   w^beta coefficients (P values) derived from separate regression analyses for each infectious agent, with individual cognitive domains as outcomes and seropositivity to infectious agents as predictors, adjusted for age, sex, and educational status.
   CMV indicates cytomegalovirus; HSV-1, Herpes Simplex virus, type 1; HSV-2, Herpes Simplex virus, type 2; MMSE, Mini-Mental State Examination; NS, not significant; TOX, Toxoplasma gondii.
TABLE 2. Temporal Changes in Cognitive Domain Composite Scores and Seropositivity for Antibodies to Infectious Agents
 ... beta (P)* ...
Cognitive Domains CMV HSV-1 HSV-2 TOX
Attention 0.0027 (NS) 0.0008 (NS) 0.0069 (NS) 0.0014 (NS)
Executive function 0.0075 (NS) 0.0043 (NS) 0.0043 (NS) 0.0074 (0.04)
Memory 0.0149 (0.04) 0.0033 (NS) 0.0238 (0.005) 0.0044 (NS)
Language 0.0083 (NS) 0.0052 (NS) 0.0086 (NS) 0.0050 (NS)
Visuospatial function 0.0123 (0.04) 0.0076 (NS) 0.0137 (NS) 0.0013 (NS)
MMSE 0.0336 (NS) 0.0208 (NS) 0.0426 (NS) 0.0664 (0.007)
   *beta coefficients (P values) derived from separate regression analyses for each infectious agent, with temporal trajectories of individual cognitive domains as outcomes and seropositivity to infectious agents as predictors, adjusted for age, sex, and educational status (negative value indicate greater relative cognitive decline).
   CMV indicates cytomegalovirus; HSV-1, Herpes Simplex virus, type 1; HSV-2, Herpes Simplex virus, type 2; MMSE, Mini-Mental State Examination; NS, not significant; TOX, Toxoplasma gondii.
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Thanks Al,


You should know if you have herpes virus type 2, genital herpes.


Herpes simplex virus type 2 (HSV-2), as well as type 1 (HSV-1) can manifest in several ways - not necessarily as genital warts, but sometimes as cold sores in the mouth, lips and nose. But you are right that HSV-1 is most commonly seen as oral sores, while HSV-2 is most often the cause of genital sores. And it was astute of you to observe that it was HSV-2 (mostly genital herpes) that was associated with the more significant rate of cognitive decline than HSV-1.


But I'd say the rate of both herpes types (especially HSV-2) is dwarfed by the prevalence of T. gondii infection (22% of general population and 50% of elderly people in this study) and especially cytomegalovirus (50-80% of general population and 83% of elderly people in this study), both of which were associated with accelerated cognitive decline in older individuals.



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This is very, very important research. I've looked into this somewhat extensively. Many of the researchers looking at herpes viruses, specifically, believe that all 8 of the herpes viruses (9 if you count the two variants of HHV-6 separately) are associated with pathology that could be construed as aging-related. I try to do everything I can to knock down my herpes virus load (I know I have HHV6 and EBV -- as does nearly everyone; not sure about the others). Lysine likely helps, and, interestingly, avoiding social isolation is important as well. [1]



[1] Loneliness Is Bad for Your Health, Study Suggests

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Lysine likely helps, and, interestingly, avoiding social isolation is important as well. [1]


[1] Loneliness Is Bad for Your Health, Study Suggests


Not to pick nits - but is it social isolation or loneliness that impairs immune function? The article you point to speaks about the dangers of loneliness. As we've discussed over on the social isolation thread you point to - it's not clear whether an introvert who is content with a socially-isolated lifestyle is at higher risk of impaired immune system function. And it will certainly be harder to pick up a virus, especially a sexually-transmitted one like HSV-2, if you're socially isolated :-).



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Not a nit but a critical distinction, as noted on the previous thread (which I meant to respond to). Thanks for the important reminder. I'm not sure we know, to be honest. I'm going to try to review Susan Pinker's references and research.



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Thanks, Dean,


The 'natural' course of HSV1 and 2 infections are fairly unique: https://en.wikipedia.org/wiki/Herpes_simplex_virus#Transmission  I did not know that about dentists, though.  "Funny" story: My wife's lab mate once was purifying HSV DNA, splashed a little in his eye, and was infected.  Ouch.  I have had oral recurrences, but not for a long time.


Thought you would like the https://en.wikipedia.org/wiki/Toxoplasma_gondii#Risk_factors_for_human_infectionre vegetarian risks, Dean.  also:


The seroepidemiology of toxoplasmosis in the lower Fraser Valley of British Columbia.
Proctor EM, Banerjee SN.
Can J Infect Dis. 1994 Sep;5(5):218-23.
PMID: 22346504 Free PMC Article
To determine the seroprevalence of toxoplasmosis in vegetarian and nonvegetarian members of different ethnic communities in the lower Fraser Valley of British Columbia.
Serum samples were collected from 2027 participants drawn from various ethnic groups and tested by elisa for the presence of immunoglobulin (Ig) G and IgM antibodies to Toxoplasma gondii. Coded questionnaires requesting information relevant to the study were completed by each participant. The study population comprised 1334 females and 693 males; ages ranged from 17 to 102 years.
Main Results:
Four hundred and nineteen (20.7%) individuals were IgG positive with titres ranging from 1:100 to 1:3200. IgM antibodies were detected in only four individuals. The seroprevalence rose with increase in age but there was no significant difference between males and females. A positive correlation was shown between ingestion of meat and between consumption of unpasteurized milk and antibodies to T gondii. Eighty per cent of females between the ages of 17 and 40, of all ethnic origins, were seronegative. Seropositivity did not differ between cat owners and non-cat owners.
Women of childbearing age are at risk of acquiring toxoplasmosis during pregnancy and of transmitting the infection transplacentally. Consumption of undercooked meat and unpasteurized milk may result in the acquisition of toxoplasmosis. Data suggest that acquisition of toxoplasmosis is more likely via environmental oocysts or cysts in food source animals than by direct contact with cats.
Keywords: ELISA, Indirect immunofluorescence, Seroepidemiology, Toxoplasmosis
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  • 2 weeks later...

The below paper suggests to me that if we CR and consequently have little carotid atherosclerosis, we are not at risk of CMV infection for cognitive decline.


Carotid atherosclerosis, cytomegalovirus infection, and cognitive decline in the very old: a community-based prospective cohort study.
Kawasaki M, Arai Y, Takayama M, Hirata T, Takayama M, Abe Y, Niimura H, Mimura M, Takebayashi T, Hirose N.
Age (Dordr). 2016 Apr;38(2):29. doi: 10.1007/s11357-016-9890-5. Epub 2016 Feb 17.
PMID: 26886582
To investigate various risk factors of cognitive decline in the very old, we studied 494 subjects over 85 years old without diagnosis of dementia at baseline from the Tokyo Oldest Old Survey on Total Health, an ongoing, community-based cohort in Japan. Cognitive function was assessed at baseline and at 3-year follow-up using Mini-Mental State Examination (MMSE). Plasma samples were assayed for levels of cytomegalovirus (CMV) immunoglobulin G (IgG) antibodies, tumor necrosis factor-alpha, interleukin-6, and blood chemistry. Carotid artery plaques were measured using an ultrasonography. In the cross-sectional analyses using Tobit regression, individuals with high carotid artery plaque score (≥5.0) had MMSE scores that were 1.08 points lower compared to those with no plaque (95 % confidence interval (CI) -1.95 to -0.20; p = 0.016), adjusted for age, sex, and education. Individuals with CMV IgG titers in the highest quartile had MMSE scores that were 1.47 points lower compared to individuals in the lowest quartile (95 % CI -2.44 to -0.50; p = 0.003). CMV and carotid atherosclerosis showed evidence of an interaction, where the association between CMV and MMSE was present only in subjects with carotid artery plaque. In the longitudinal analyses using linear regression, carotid atherosclerosis, smoking, low grip strength, and poor activities of daily living (ADL) status were associated with faster cognitive decline, adjusted for age, sex, education, and baseline cognitive function. Our findings suggest that carotid atherosclerosis is consistently associated with low cognitive function in the very old and modifies the association between latent CMV infection and cognition.
Atherosclerosis; Cognitive decline; Cytomegalovirus; Inflammation; Very old
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First off, thanks for posting the DOI number for this paper (PMID: 26886582 DOI: 10.1007/s11357-016-9890-5), since searching by DOI number at LibGen for previously accessed sci-hub.io papers works, but searching by PMID doesn't. Here is the LibGen link to the full text of the paper.


The abstract, and your description, are a little by obscure (cryptic) about what may be going on between CMV, atherosclerosis and cognitive decline. From the full text, here is the authors' summary:


All together, these epidemiological and experimental evidences suggest that atherosclerosis is one mechanistic link between CMV infection and cognitive impairment of the very old, who are at high risk for immunosenescence.


In other words, they think CMV infection results in increased atherosclerotic plaques, which in turn impair blood flow to the brain leading to micro-strokes or other damage that manifest as cognitive impairment. So while you are technically correct, at least by one interpretation when you say:


The below paper suggests to me that if we CR and consequently have little carotid atherosclerosis, we are not at risk of CMV infection for cognitive decline.


it is a little confusing when you say "we [CR practitioners] are not at risk of CMV infection for cognitive decline." More accurately, we, like everyone else, are at risk for CMV infection. But unlike the average American, our healthy diet/lifestyle helps keep our arteries pretty clean. So the chronic, systemic inflammation resulting from a CMV infection is unlikely to result in significant plaque buildup in our arteries, and so presumably won't result in cognitive decline or heart disease.


A clearer re-statement of your comment would seem to be (my edit):


The below paper suggests to me that if we CR and consequently have little carotid atherosclerosis, we are not at risk of CMV-induced infection for cognitive decline.


But it still seems like a good idea to watch out for, and avoid if possible, CMV infection, despite the protection from some of its negative effects that our practice of CR would seem to provide us.



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  • 2 months later...



I've been doing a little more homework prior to the CR Conference. I've looked at the background and publications of Dr Janko Nikolich-Žugich from the University of Arizona (UA), who'll be speaking at the conference (schedule here) and who we are hoping to engage with in a study of CR and immunity in humans. He seems to be quite the expert in the area, and is very interested in the topic we've discussed on this thread and elsewhere - namely that CR may be good for keeping  the immune system from generating systemic inflammation and maintaining its function into old age, but at the same time may hamper the body's ability to muster a strong immune response to combat an infection once it has taken hold. From this UA press release:


“While calorie restriction appears to improve immune function and homeostasis in old animals, the few infectious challenge experiments suggest increased susceptibility to infection. Our exploratory proposal aims to test the hypothesis that calorie restriction and drugs that trick the cells into thinking that there is not enough food, such as Rapa[mycin], could be deleterious for protective immunity, because they may curtail full development of immune responses,” notes Dr. Nikolich-Žugich.


I discussed one of his papers (PMID 25424641) in this post, which showed both CR and rapamycin inhibit the ability of mice to fend of West Nile Flu virus, dying sooner and more often once infected than ad lib fed controls.


He's also been investigating how chronic symptomless infections (like Cytomegalovirus, discussed earlier in this thread), may negatively impact long-term health and longevity [1]. 


I'm looking forward to hearing about his latest research, and hopefully collaborating with him as a subject in the CR & immunity arm of his current research study.





[1] J Immunol. 2014 Mar 1;192(5):2143-55. doi: 10.4049/jimmunol.1301721. Epub 2014

Feb 5.
Aging and cytomegalovirus infection differentially and jointly affect distinct
circulating T cell subsets in humans.
Wertheimer AM(1), Bennett MS, Park B, Uhrlaub JL, Martinez C, Pulko V, Currier
NL, Nikolich-Žugich D, Kaye J, Nikolich-Žugich J.
Author information: 
(1)Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ
The impact of intrinsic aging upon human peripheral blood T cell subsets remains 
incompletely quantified and understood. This impact must be distinguished from
the influence of latent persistent microorganisms, particularly CMV, which has
been associated with age-related changes in the T cell pool. In a cross-sectional
cohort of 152 CMV-negative individuals, aged 21-101 y, we found that aging
correlated strictly to an absolute loss of naive CD8, but not CD4, T cells but,
contrary to many reports, did not lead to an increase in memory T cell numbers.
The loss of naive CD8 T cells was not altered by CMV in 239 subjects (range 21-96
y), but the decline in CD4(+) naive cells showed significance in CMV(+)
individuals. These individuals also exhibited an absolute increase in the
effector/effector memory CD4(+) and CD8(+) cells with age. That increase was seen
mainly, if not exclusively, in older subjects with elevated anti-CMV Ab titers,
suggesting that efficacy of viral control over time may determine the magnitude
of CMV impact upon T cell memory, and perhaps upon immune defense. These findings
provide important new insights into the age-related changes in the peripheral
blood pool of older adults, demonstrating that aging and CMV exert both distinct 
and joint influence upon blood T cell homeostasis in humans.
PMCID: PMC3989163
PMID: 24501199
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Janko Nikolich-Zugich's 2016 Conference Talks - Metabolism, Nutritional Forces and Immunity During Aging


Since Dr. Nikolich-Zugich (henceforth abbreviated N-Z) spoke about nutrition, aging and immunity, and a lot about chronic infection, I thought this thread was the appropriate place to report on his conference presentation, and some interesting implications of his work for our health practices.


Immune System Overview


Dr. N-Z first gave an overview of how the immune system works. He spoke of two aspects of our immune system, the innate vs. adaptive immune system. The innate immune system is non-specific and designed to globally slow down pathogens. He didn't mention it specifically, but the body's fever response is part of the innate immune system, by making the body a less friendly place for pathogens to grow.


But his focus is on the adaptive immune system, which needs to be flexible and fast-acting, to cope with incredibly variable and fast multiplying bacteria and viruses. To do this, the body keeps around a small set of specialized cells called T-cells, which are among the fastest dividing cells in the body.


We start with a pool of "naive" T-cells - not specialized for any particular bacteria. Through a complicated process he didn't go into, when exposed to a pathogen (virus or bacteria) these naive T-cells get imprinted with the signature of the pathogen, enabling them to target them for destruction. By specializing in this way, initially naive T-cells turn into effector T-cells that multiply very rapidly during an infection to help the body combat it. After (hopefully) successfully squelching the infection, the T-cells go quiet and most of them are recycled. But a few of them stick around as "memory T-cells", in case that specific pathogen is ever encountered again so our immune system will be ready to ramp up another immune response quickly.


Aging and Immunity


That's how things are supposed to work. But with aging, CR and/or infection by a persistent infection (especially Cytomegalovirus or CMV - see below), things don't always work so well.


First off, as we age we make fewer naive T-cells (in our thymus, which declines with age) to imprint on new infections. So vaccines don't work as well in the aged because older people don't have the T-cells to imprint on them. And the T-cells older folks do have don't work as well. So as people get older, they become more susceptible to coming down with infections, and also less able to ramp up an effective immune response if/when they do get sick. 


Persistent infections by pathogens that are able to evade complete eradication by the immune system and so remain dormant and flare up occasionally, can be particularly detrimental on immune system health, especially as we age. Cytomegalovirus (CMV) is a herpes virus which is especially common in people, and harmful in this regard. See more below.


CR & Immunity


CR makes many immune system parameters look better - thymus looks healthier, more naive T-cells etc. As a result, CR rodents have a better early response to an infection challenge. But alas, all is not so rosy. The reason appears to be that mounting a strong effective response to an infection is incredibly energy intensive. In order to reproduce rapidly, T-cells switch from efficient (but slow) oxidative phosphorylation (oxphos) metabolism to faster (but wasteful) glycolytic metabolism. And to do this and divide rapidly requires a large store of energy, which CR rodents (and presumably CRed people) don't have. So as we saw in Dr. N-K's paper in the previous post in this thread, CR mice exposed to an flu infection are much more likely to die than ad lib fed mice. But unlike people who die from respiratory complications as a result of the flu, mice die of flu as a result of weight loss, so it isn't (or wasn't) clear how relevant these results were to people.


He built a better model of immune response that involved a different virus - West Nile Virus (WNV). Turns out, CR increases mortality in mice exposed to WNV too, so unfortunately this seems to confirm that CR impairs an animal's ability to combat an already-contracted infection.


Rapamycin (which, like CR, downregulates mTOR) has the same effect - causing the immune system to cope less effectively with an infection. Mice treated with rapa died earlier and more often than untreated mice when exposed to influenza or WNV.


In short, while rapa (and obviously, CR) may extend lifespan in germ-free mice in a protected lab environment, they make them less capable of fighting off infections they might encounter in the "real world".



Part II  - Inflammation and Aging

Dr. N-K also as a strong interesting in the effects of aging and chronic infection on the immune system and inflammation.


Inflammation is good in acute form - it is necessary to deal with stress. It basically is the way the body masses it's forces to deal with damage or threat, including infections.

But chronic inflammation is bad news. Inflammation makes you more susceptible to the diseases of aging - CVD, metabolic syndrome, cancer, neurodegenerative diseases.
Where does chronic inflammation come from?
  1. immune senescence - "trigger happy" immune cells.
  2. Microbes - e.g. a leaky gut
  3. Adipose tissue can be very inflammatory - secretes cytokines
  4. Senescent cells - can spew out inflammatory markers
He's focused on persistent infections as source of inflammation. In particular, Cytomegalovirus (CMV), which is a herpes virus. 60% of adults, and 80-90% of elderly have a latent CMV and don't even know it.
CMV infection is associated with immune aging, reduced lifespan, and increased CVD. CMV is a "stealth" virus - hides from the immune system only to flair up again in cycles of latency and reactivation. Very species specific. CMV becomes incorporated into arterial plaques when macrophages "eat" the virus and then get stuck in artery walls. 
CMV might be helpful in youth - putting immune system in heightened state of alertness to respond better to other viruses. But CMV is never eliminated. As of now once you've got it you've got it for life. It keeps stimulating immune system repeatedly. So lots of T-cells get imprinted to handle CMV, using up the body's limited supply of naive T-cells. In older folks, upwards of 50% immune cell may become tailored for CMV (as "memory T-cells"), which may impair the body's ability to recognize and fight other infections.
He did study of immune system with people with and w/o CMV. Naive cells do go down with age - in everyone, not just CMV-positive folks. Memory cells don't go up with age in either CMV-positive or CMV-negative folks - contrary to expectations. But CMV-positive folks have more memory cells (specifically tuned for CMV) and therefore more circulating inflammatory cytokines. Unlike other herpes viruses, CMV is distributed across body, not just locally, making it especially detrimental.  So it would be better to avoid CMV infection. Unfortunately most adults have it, especially the elderly.


Here is where people who have read to the end of this post get rewarded - yeah for you!


I asked him in the Q&A afterwards about testing for CMV, and he said there is a blood test, although not much you can do if you test positive for CMV, since there isn't an effective treatment to eliminate it. Surprisingly, my favorite online, self-service blood testing resource (privatemdlabs.com) doesn't appear to offer a test for CMV.  But fortunately, David Stern was kind enough to come up to me after Dr. N-K's talk with a great suggestion. He said that if I donate blood, I can call the collection organization (or me it's Central Blood Bank) and ask them for my CMV status, since apparently hospitals don't give CMV-positive blood to kids or immunocompromised people who aren't already infected with CMV - see below.


I called first thing this morning, and it took them about 30 seconds to look up my CMV status. I'm CMV-negative - yeah! That's pretty unusual for someone my age. Coupled with the fact that my blood type is O- (universal donor blood type), it's no wonder they are always asking me to donate, which I'm happy to do.


Doing a little digging, I was shocked to find that the CMV status of the recipients of blood products isn't more widely taken into account when doing transfusions (e.g. during surgery). Given the apparent negative health consequences that Dr. N-K's research shows can result from chronic CMV infection, one would hope that hospitals wouldn't give CMV-positive blood products to any patient who was lucky enough to be CMV-negative. But unfortunately, this doesn't appear to be the case. This Medscape page says that CMV-negative blood products are only explicitly called for in cases of patients who are "CMV naïve and profoundly immunocompromised". These folks including:

  • Pregnant women and their fetuses (to prevent congenital CMV)
  • Low birthweight infants
  • Hematopoietic progenitor cell transplant recipients
  • Solid-organ transplant recipients
  • Severely immunosuppressed patients
  • Congenital immunodeficiency patients
  • HIV-infected patients

For other, immunocompetent folks, it seems like a different story, both in the US and Canada. This Canadian document entitled Transfusion Medicine Best Practices: Guidelines for CMV Negative Blood Components, only talks explicitly about avoiding giving CMV-positive blood products in the case of Intrauterine transfusion (i.e. transfusions into babies still in the womb), neonates under 28 days of age and elective transfusion of CMV seronegative pregnant women.


Just to make sure, I texted an MD friend of mine to ask about it. Here is the transcript of our conversation:


Me: Here is a doctor question for you. Would they transfuse CMV-positive blood products into someone who is CMV-negative but not immunocompromised?


MD Friend: We try not to, but 40-90% of donors are CMV-positive, so may not be enough in pool. Priority given to CMV-neg premies or those with immunodeficiencies.


Me: Is it standard practice to test for CMV for potential transfusion patients?


MD Friend: I don't think so. Not for an immunocompetent patient.


So there you have it. If you end up needing a blood transfusion, it seems that there is a pretty good chance you'll receive CMV-positive blood products unless you are unfortunate enough to also be immunocompromised.


Personally, as someone who now knows he is CMV-negative, I will go to pretty great lengths to preserve that status, given the apparent negative health implications of chronic CMV infection.  If I were going in for surgery where a blood transfusion might be required, I'd talk to my doctor to see if I can make sure they use CMV-negative blood products, or better yet, if it's not an emergency, I'd do an autologous blood donation ahead of time so they can use my own blood if/when a transfusion becomes necessary.


According to the Mayo Clinic, other strategies for avoiding CMV infection are basically good hygiene practices, including:

  • Wash your hands often.
  • Avoid contact with tears and saliva when you kiss a child.
  • Avoid sharing food or drinking out of the same glass as others.
  • Be careful with disposable items.
  • Clean toys and countertops.
  • Practice safe sex.

So there you go, science that is both interesting, relevant to humans, and actionable. That's what I like to discover!



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There is a new study out [1] pointing to a disturbing but seemingly plausible causal pathway between chronic infection and Alzheimer's disease. Basically, it found that amyloid-β peptide (Aβ), the stuff that eventually forms the plaques characteristic of Alzheimer's disease, may serve as antimicrobial agent which the brain employs to protect itself against fungal or bacterial infections that somehow get across the blood-brain barrier. But eventually things get out of hand, and the Aβ ends up doing more harm than good, by forming harmful plaques.


This model is consistent with the observed association between cognitive decline and chronic infection with viruses like CMV and HSV-1 and HSV-2, which was the focus of the opening post in this thread. All the more reason to check one's status for these infections, and lighten one's viral load if possible.





[1] Science Translational Medicine  25 May 2016:

Vol. 8, Issue 340, pp. 340ra72 DOI: 10.1126/scitranslmed.aaf1059
Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease
Deepak Kumar Vijaya Kumar1,*, Se Hoon Choi1,*, Kevin J. Washicosky1,*, William A. Eimer1, Stephanie Tucker1, Jessica Ghofrani1, Aaron Lefkowitz1, Gawain McColl2, Lee E. Goldstein3, Rudolph E. Tanzi1,† and Robert D. Moir1,†


The amyloid-β peptide (Aβ) is a key protein in Alzheimer’s disease (AD) pathology. We previously reported in vitro evidence suggesting that Aβ is an antimicrobial peptide. We present in vivo data showing that Aβ expression protects against fungal and bacterial infections in mouse, nematode, and cell culture models of AD. We show that Aβ oligomerization, a behavior traditionally viewed as intrinsically pathological, may be necessary for the antimicrobial activities of the peptide. Collectively, our data are consistent with a model in which soluble Aβ oligomers first bind to microbial cell wall carbohydrates via a heparin-binding domain. Developing protofibrils inhibited pathogen adhesion to host cells. Propagating β-amyloid fibrils mediate agglutination and eventual entrapment of unattached microbes. Consistent with our model, Salmonella Typhimurium bacterial infection of the brains of transgenic 5XFAD mice resulted in rapid seeding and accelerated β-amyloid deposition, which closely colocalized with the invading bacteria. Our findings raise the intriguing possibility that β-amyloid may play a protective role in innate immunity and infectious or sterile inflammatory stimuli may drive amyloidosis. These data suggest a dual protective/damaging role for Aβ, as has been described for other antimicrobial peptides.
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I don't know about this. If cognitive decline - or more acutely Alzheimer's disease - etiology was primarily environmental, especially mediated by viruses, then how would it be possible to correlate genes to the frequency of Alzheimer's? Are E4/E4 folks especially vulnerable to viruses?


Since we are talking about rate of accumulation of amyloid plaques, I have a nifty paper I wanted to post, so I'll just make a separate post.

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Obviously Alzheimer's is a very complicated disease, involving many different causal factors, including both genetic and (apparently) environmental factors. Infections are obviously not the only cause.


It's like heart disease - having familial hypercholesterolemia (or being an APOE4 carrier, for that matter), increases one's risk for CVD, but so does a poor diet, lack of exercise, and, as Al pointed out in the paper he posted above (PMID 26886582), so does chronic infection with CMV.



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So I guess staying a virgin for life is a good idea then? :D


But wait... wouldn't one then expect CMV to increase at the fastest rates in the youngest people, who are most sexually active? From a cursory glance, it seems that rates still significantly increase with age even in older people?

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