DNA Methylation Clocks' Predictive Capacity for Aging Phenotypes and Healthspan

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.

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

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.

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

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.

I have a 23andMe test waiting to be used, but "privacy fears" have kept me from using it. Found My Fitness (Dr. Rhonda Patrick) offers tests that ostensibly help individuals shape their health strategies: https://www.foundmyfitness.com/genetics

So, Ask HN: is my paranoia unfounded? Is my DNA already catalogued and the cat is out of the bag? Fortunately I've committed no crimes of significance, so I'm not I'm not worried about being identified like that.

The crux of the problem here is that most people don’t want to really put much effort into the basics. All these things are to improve things at the edge, like a pro runner choosing better cleats.

Exercise and diet alone will lower all cause deaths risk by something like 50%. But no one will do this simple thing because who wants to believe that doing heavy squats and cutting out refined carbs will help?

don’t hold me to that number it’s somewhere near there for %.

Unfortunately the relationship between clock readouts and actual health state is tenuous at best, and is really more of a postulate than an established fact.

It is true that Horvath and others have shown that clock deltas (between predicted and chronological age) correlate with all-cause mortality. There has been surprisingly little work on clock deltas and specific disease risk.

But these are correlational or observational studies. What is not known is whether, or how often, an intervention that changes the clock will also change lifespan or healthspan. There are far too many grants and papers that just assume this is true. Usually the argument is something like this: intervention X improves health, intervention X lowers clock age, therefore the clock is a good biomarker of aging.

The classical Horvath clock has something like 350 loci all spread out in the genome, often in regions that have no obvious functional significance.

Imagine the extreme case (which has been the subject of more than one grant proposal): take one of the clock loci 100 kbp from the nearest gene, forcibly alter its methylation state specifically. Will this change clock age? By definition, yes. Will it alter health at all? Very likely not. People seem unaware of the almost certain fact that these loci are not causal in aging, they are readouts of upstream biological states.

Also, there are numerous inconvenient facts, such as the fact that the if you compare groups of the same age, one group with and one without various neurological diseases such as Alzheimer's, the group with neurological disease appear to be younger by the clock.

I would beware of this area, there is so much hype around it and claims have far outstripped evidence by this point.