Methylation, aging and ME/CFS

[richvank]

Hi, all.

About ten years ago, when the late physicist, Prof. Edward Teller, was still alive, but in his 90s, I had a conversation with him in his office. I told him that I was working on CFS, and he asked me to tell him about it. I described some of the symptoms, and he asked, "Is that like old age?"

This question has stuck with me since. I had to agree that there are some similarities.

Now I've just heard about a paper that I think is very interesting. The researchers compared the degree of methylation of the whole genome for a newborn, a 26-year-old, and a 103-year-old person. They found that the genome-wide methylation decreased as the age increased. This likely has major effects on the expression of many of the genes, and could be a major contributor to the process of aging.

The full paper can be found here:

http://www.pnas.org/content/109/26/10522.full.pdf+html

Note especially Figure 1A, in which the intensity of the blue color indicates the degree of methylation, starting with the newborn on the inside circle, then the 26-year-old, and finally the 103-year-old at the outer circle.

Since we know from lab testing that there is a methylation deficit in ME/CFS, I suspect that it will be manifested as a lowering of the genome-wide DNA methylation status. Perhaps this is the cause (or a cause) of the similarities between ME/CFS and aging. I think the CDC is doing a study of genome-wide methylation in ME/CFS, so hopefully we will find out soon whether this idea holds up.

Best regards,

Rich

 

[Little Bluestem]

This is very interesting. I have wondered if both of my elderly parents have ME/CFS, since there is some evidence of susceptibility within families. More likely, it is just that they are elderly.

 

[Lou]

Hi, all.

About ten years ago, when the late physicist, Prof. Edward Teller, was still alive, but in his 90s, I had a conversation with him in his office. I told him that I was working on CFS, and he asked me to tell him about it. I described some of the symptoms, and he asked, "Is that like old age?"

This question has stuck with me since. I had to agree that there are some similarities.

Now I've just heard about a paper that I think is very interesting. The researchers compared the degree of methylation of the whole genome for a newborn, a 26-year-old, and a 103-year-old person. They found that the genome-wide methylation decreased as the age increased. This likely has major effects on the expression of many of the genes, and could be a major contributor to the process of aging.

The full paper can be found here:

http://www.pnas.org/content/109/26/10522.full.pdf html

Note especially Figure 1A, in which the intensity of the blue color indicates the degree of methylation, starting with the newborn on the inside circle, then the 26-year-old, and finally the 103-year-old at the outer circle.

Since we know from lab testing that there is a methylation deficit in ME/CFS, I suspect that it will be manifested as a lowering of the genome-wide DNA methylation status. Perhaps this is the cause (or a cause) of the similarities between ME/CFS and aging. I think the CDC is doing a study of genome-wide methylation in ME/CFS, so hopefully we will find out soon whether this idea holds up.

Best regards,

Rich

Hi Rich,

In what way is this helpful? I mean, we tend to have ENOUGH on our plate as it is, and it doesn't explain why many of us look healthy, some younger than actual age.

Sure you meant well, but it seems to me since there seems to be a lack of elixers --especially ones that work for us more than once-- this only gives us more about which to worry, not a useful thing.

Best regards,

Lou

 

[richvank]

Hi, Lou.

Sorry. Just trying to connect things together and make sense of it all. One good thing that might come out of this is that there is a lot of clout behind aging research, probably because some of the older people have a lot of resources and connections, and would like to live longer if they are healthy. So there may be research directed at trying to increase methylation in the elderly, and ME/CFS might get some helpful spinoff from that, just as we benefit from autism research.

In the meantime, I think we have good reason to support methylation treatment in ME/CFS, based on what we already know. I don't know if you have tried the simplified methylation protocol, but if not, it might be something to consider.

I think you raised a good issue about why people with ME/CFS often look younger than their ages. How does this jibe with the connection I suggested? I don't have an answer for that.

Best regards,

Rich

 

[Ema]

I think you raised a good issue about why people with ME/CFS often look younger than their ages. How does this jibe with the connection I suggested? I don't have an answer for that.

Best regards,

Rich

I always thought it had something to do with Ehler-Danlos in my case. I've always looked 10 or so years younger than my age from what others tell me. But now I just look tired!

EDS is supposedly a risk factor for ME/CFS. I wonder if it has something to do with how the connective tissue is made?

Ema

 

[richvank]

Hi, Ema.
I don't know. Maybe so. EDS does involve the collagen.
Best regards,
Rich

 

[jeffrez]

Finally the answer as to why I feel like a 90-year old. Actually, most 90-yos that I've seen have more energy and less PEM. : P

 

[Little Bluestem]

I think you raised a good issue about why people with ME/CFS often look younger than their ages. How does this jibe with the connection I suggested? I don't have an answer for that.

I have wondered if it is because our metabolism is slowed down, like those rats that live longer when their food intake is cut. I have been surprised at how little food I can eat and still not lose weight. Nor do I develop low blood sugar as long as the calories are spread throughout the day. Like Ema, I have reached the point where the fatigue makes me look haggard, and thus older.

 

[merylg]

I DO also think there's a definite connection between ME/CFS and Connective Tissue Disorders (?Collagen & Collagen/Vascular connection). My mother had scoliosis, arthritis, migraines & Type 2 Diabetes. Myself and my children have mild scoliosis & I suffer migraines, arthritis/enthesitis. Two children have assymetric rib-cage. One has hypermobile wrists & flat feet. One has hypermobile end finger joints (weird!)

The fatigue I feel definitely feels like a premature aging & when my brother had a fatigue-like crash I remember him saying "I feel really old"....but he's bounced back again.
Looking back my condition has behaved like a mitochondrial issue...burn crash recover...burn crash recover.

 

[place]

Hi rich,
It been a crazy day and did not get to read all the posts but, I have done infertility treatments and my eggs are the quality of a 45 year old..... i'm 36 =( . Some women have this issue but it's really rare, really rare.

 

[biophile]

Off-topic to aging but still related to methylation and disease, richvank may enjoy this recent paper if not already aware of it. Basically, the human brain is less methylated than the chimpanzee brain and this may help to explain differences in vulnerabilities to neurological disorders, psychological disorders, and cancers.

Divergent Whole-Genome Methylation Maps of Human and Chimpanzee Brains Reveal Epigenetic Basis of Human Regulatory Evolution.

Zeng J, Konopka G, Hunt BG, Preuss TM, Geschwind D, Yi SV.

The American Journal of Human Genetics, 23 August 2012 doi:10.1016/j.ajhg.2012.07.024

DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits.

http://www.cell.com/AJHG/retrieve/pii/S0002929712004107

 

[richvank]

Hi, biophile.

Very interesting! Thanks for posting this.

So, does this mean that if we overmethylate, we will turn into monkeys?

Best regards,

Rich

 

[greenshots]

To me, lack of knowledge is a dangerous thing. I don't find more knowledge burdensome, it just explains more of the puzzle. I sure don't expect any magic elixers or simple, all-in-one answers anytime soon. In the meantime, we plug away and learn what we can, when we can.

 

[Sasha]

I think you raised a good issue about why people with ME/CFS often look younger than their ages. How does this jibe with the connection I suggested? I don't have an answer for that.

I'm constantly told I look about 10-15 years younger than my actual age (50) and I have always assumed it's because I was confined to bed for 10 years during my first illness and almost entirely to the house for the 5 years of my latest relapse, thereby avoiding a lot of photo-ageing by being indoors.

However, I saw on a documentary recently that the wavelengths of light that cause skin ageing (can't remember if that's UVA or UVB) pass through glass unfiltered so maybe that theory's no good - I must still be getting a ton of light through the windows.

 

[Lou]

To me, lack of knowledge is a dangerous thing. I don't find more knowledge burdensome, it just explains more of the puzzle. I sure don't expect any magic elixers or simple, all-in-one answers anytime soon. In the meantime, we plug away and learn what we can, when we can.

Truth is, I respect Rich greatly as well as his tireless effort on our behalf, and he's proven often on this forum he can handle a little disagreement. Yes, it disappointing/irritating to some when authority is questioned. I get it. But the same goes when context is stretched to parallel a response.

Cherry-picking your context (was there anywhere a hint in my post that knowledge, overall, is a dangerous thing?) one could say lack of knowledge by a three-year old child of how to open a tamper-free bottle of 500mg niacin is actually a good thing. A lot of other examples could be given. But you were obviously not referring to always dangerous.

The musing of Professor Teller is perhaps beneficial, perhaps not. And methylation (not saying Rich ever said it was) by far is not the only thing decreasing as we, or anybody else, age/ages. Reference to elixars was clearly a throwoff, don't know how it morphed into something magical.

I'll back off, could be a good thing to explore this possible aging relationship to methylation, but I never said knowledge was a dangerous thing, and it doesn't seem particularly accurate to imply I did.

 

[greenshots]

obviously,this hit a sore spot for you as well. Your responses seem a bit overly dramatic but my point is that the answers you seek won't be easily found. Nor will any one article explain them. When your plate is full, its best to avoid clicking on further links to reduce your burden. I think I can safely say we've all been there & understand how overwhelming it is.

Truth is, I respect Rich greatly as well as his tireless effort on our behalf, and he's proven often on this forum he can handle a little disagreement. Yes, it disappointing/irritating to some when authority is questioned. I get it. But the same goes when context is stretched to parallel a response.

Cherry-picking your context (was there anywhere a hint in my post that knowledge, overall, is a dangerous thing?) one could say lack of knowledge by a three-year old child of how to open a tamper-free bottle of 500mg niacin is actually a good thing. A lot of other examples could be given. But you were obviously not referring to always dangerous.

The musing of Professor Teller is perhaps beneficial, perhaps not. And methylation (not saying Rich ever said it was) by far is not the only thing decreasing as we, or anybody else, age/ages. Reference to elixars was clearly a throwoff, don't know how it morphed into something magical.

I'll back off, could be a good thing to explore this possible aging relationship to methylation, but I never said knowledge was a dangerous thing, and it doesn't seem particularly accurate to imply I did.

 

[newradost]

Hi Rich, that was my statement also but everyone laught.... My grandma has trombosis (this is MTHFR related & so proved) and severe koksatrosa (7cm difference between foot). She died at her 85 very slowly and in autism like symptoms. She was very sensitive and loud person and it was very unusual to her to be stone face and unemotional..

That's how it happened - she was having a flue and doctors put her at antibiotics. Then she became ill for a long and my father took her to live at the city. She was supposed to change her bedding time and to live at smoked environment and the doctors put her at pills and my father fed her with sausages and croassants - something that she was not fond of because her food was growing in her own garden. She was in this condition for about 2 years and died slowly not being able to walk, sleep and get up from bed. The doctors said that her hearth is so strong and that's why she is still alive. SHe has no diagnosis and doctors said that simply her time has come. In my eyes - poor methylation....

 

[Lou]

Hi greenshots,

Lol, after rereading those posts tend to agree on 'a bit overly dramatic', thanks for pointing that out. Would-be writer problem.

If I could just kindly redirect to your posts and mention perhaps a bit didactic. As part of the Incline Village outbreak in the 1980's I've already been down a few of those roads.

 

[Lou]

Hi Rich,

There was something Dr. Cheney once mentioned that appeared (I think) to say just the opposite about aging and me/cfs. A lot of looking, but I can't find it now, think it must have been in his newsletter and my subscription has expired. Anyway, seems he was discussing stem cell treatment and remarked that if and when a cure was found for me/cfs our 'restart', or similar term, would be from a somewhat 'preserved' (that's not the word he used, but something similar) state. Sorry I can't be more specific, just wondering if you or anybody else here happens to recall what exactly he said.

 

[Sushi]

I always thought it had something to do with Ehler-Danlos in my case. I've always looked 10 or so years younger than my age from what others tell me. But now I just look tired!

EDS is supposedly a risk factor for ME/CFS. I wonder if it has something to do with how the connective tissue is made?

Ema

I haven't been reading this whole thread, so sorry if this has been raised before. I have Ehlers-Danlos, look younger than I am and believe that they have found certain gene associations with EDs. My parents had it too.

Sushi