5 ms·

Ok, ELI5 anyone? I have a homozygous MTHFR 677 C>T mutation, e.g. my body methylates at like 20-30% efficiency unless I supplement with methylated B-12, e.g. me

by newobj 6y ago

Ok, ELI5 anyone? I have a homozygous MTHFR 677 C>T mutation, e.g. my body methylates at like 20-30% efficiency unless I supplement with methylated B-12, e.g. methylcobalamin. Is this study good news for me or bad news for me?

saas_sam 6y ago
Semi-related but check out the research on creatine supplementation too. It's nigh impossible to get the full amount of creatine in your diet daily -- your body does a good job creating what it needs via methylation. You can free up methyl groups if you supplement with it. But yeah, Google for yourself IANAD.
keyboardhitter 6y ago
I would encourage you to look outside of simple "good v. bad" when it comes to medical sciences, and discourage anyone from doing newobj's research for them, unless a medical professional online here can shed light with proper terminology
m0llusk 6y ago
This material is at the edge of my comprehension, but it seems that genetic variation is likely not directly relevant to this specifically. What appears to be happening here is that gene activation patterns which work through methylation of DNA strands leave a kind of footprint behind over long periods of repeated gene activations. This is driven by gene activations which are required for basic biological function. If your genes are not being activated through methylation then you would have a range of problems with ordinary body function. It is possible that you might have generally reduced DNA methylation which could lead to slowed biological aging, but that would cause illness up front so the situation is kind of complicated.
ethanwillis 6y ago
There are two things: - DNA Methylation - DNA Acetylation Methylation downregulates a gene's expression. Acetylation upregulates a gene's expression. In any case, over your lifetime methylation profiles of your genetics can vary, generally increasing. Methylation of your cells isn't something that happens in every tissue at the same rate. So you actually need to define a biological clock based on methylation over time for all the different tissues. Then you can also build clocks for 2 or more tissues, or the whole organism... maybe https://en.wikipedia.org/wiki/Epigenetic_clock https://en.wikipedia.org/wiki/Epigenetic_clock
xab31 6y ago
These clocks are machine learning models that predict a person's age based on the global methylation state of their genome. What is undisputed is that these clocks predict with good accuracy. What is hotly contested is what biological meaning, if any, specific methylated loci have. These clocks are mainly being used for research, but one real-world application they are being used for is life insurance companies. If you are 60, but your methylome makes you appear 50, then you'll get a discount, as it is assumed that your health state will be closer to that of a 50-year-old. So if you have a systematically distorted methylome, and you want to buy life insurance, the clock could be good news or bad news for you, depending on how your mutation affects the clock readout. It used to be dogma that genomic hypomethylation occurs with age, or in other words, that methylation decreases as you age. It is now thought to be more complicated than that, but...if it is even partially true, that would imply that lower methylation levels would be associated with a higher age on the clock. So probably you would not get a discount, sadly.

by newobj 6y ago

saas_sam 6y ago

Semi-related but check out the research on creatine supplementation too. It's nigh impossible to get the full amount of creatine in your diet daily -- your body does a good job creating what it needs via methylation. You can free up methyl groups if you supplement with it. But yeah, Google for yourself IANAD.

keyboardhitter 6y ago

I would encourage you to look outside of simple "good v. bad" when it comes to medical sciences, and discourage anyone from doing newobj's research for them, unless a medical professional online here can shed light with proper terminology

m0llusk 6y ago

This material is at the edge of my comprehension, but it seems that genetic variation is likely not directly relevant to this specifically. What appears to be happening here is that gene activation patterns which work through methylation of DNA strands leave a kind of footprint behind over long periods of repeated gene activations. This is driven by gene activations which are required for basic biological function. If your genes are not being activated through methylation then you would have a range of problems with ordinary body function. It is possible that you might have generally reduced DNA methylation which could lead to slowed biological aging, but that would cause illness up front so the situation is kind of complicated.

ethanwillis 6y ago

There are two things: - DNA Methylation - DNA Acetylation Methylation downregulates a gene's expression. Acetylation upregulates a gene's expression. In any case, over your lifetime methylation profiles of your genetics can vary, generally increasing. Methylation of your cells isn't something that happens in every tissue at the same rate. So you actually need to define a biological clock based on methylation over time for all the different tissues. Then you can also build clocks for 2 or more tissues, or the whole organism... maybe https://en.wikipedia.org/wiki/Epigenetic_clock https://en.wikipedia.org/wiki/Epigenetic_clock

xab31 6y ago

These clocks are machine learning models that predict a person's age based on the global methylation state of their genome. What is undisputed is that these clocks predict with good accuracy. What is hotly contested is what biological meaning, if any, specific methylated loci have. These clocks are mainly being used for research, but one real-world application they are being used for is life insurance companies. If you are 60, but your methylome makes you appear 50, then you'll get a discount, as it is assumed that your health state will be closer to that of a 50-year-old. So if you have a systematically distorted methylome, and you want to buy life insurance, the clock could be good news or bad news for you, depending on how your mutation affects the clock readout. It used to be dogma that genomic hypomethylation occurs with age, or in other words, that methylation decreases as you age. It is now thought to be more complicated than that, but...if it is even partially true, that would imply that lower methylation levels would be associated with a higher age on the clock. So probably you would not get a discount, sadly.