Really looking forward to some of the startups in this area, specifically companies that A) help you measure how healthy you are, and then B) help direct you on how to optimize your own health. One would think this is a job for our current medical system, but preventative care and true health and longevity optimization get very little attention compared to treating problems as they come up and settling for mediocrity.
There's a lot of interesting people that work on minimizing their biological age (sometimes measuring it with simple blood metrics that correlate with youth, and other times with more advanced and speculative ones like DNA methylation tests), and it's definitely an important, neglecting, and upcoming area. The downside is that to do a good job of maximizing your health and lifespan like this, it takes a lot of work, time, money, and research. For that reason I'm hoping some startups in this area do some amazing work and really start to make the field of healthspan and lifespan optimization more mainstream and accessible.
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.
Not 23andMe but Ancestry.com was just bought by Blackstone [0]. I would say any privacy concerns are very valid if not invalidated by your DNA already being out there as you suggested.
I don't think it's unfounded, since once these companies have your DNA, they can keep it forever, share it, or even lose it in a data breach, and presumably over the next years/decades we will be able to make DNA information about you significantly more valuable.
In general there doesn't yet appear to be common significant gains that can be made from the DNA tests available. Sometimes you will be lucky and find you're at high risk of certain things, but the vast majority of the information won't help you much. You still need to eat and exercise well either way.
Until this changes, and we can actually do a decent job of offering personal recommendations based off of one's DNA, you're likely better off getting a lot of blood tests and working from there.
The main thing is that most of what DNA variations indicate are complex and general factors for various biological processes. In any case where a DNA variation has significant implications such as probability of disease there is a good chance that there will be other related complications and symptoms that appear early in disease progression. As with almost all disease, being careful to get good nutrition, exercise, and sleep goes a very long way. Furthermore, there have not been really any cases of people being bribed or somehow held accountable for their genetic variation. This is especially true now that most health insurance is sold without respect to preexisting conditions.
23andMe will use your DNA to develop new drugs or treatments to help the general population. If you're comfortable with that, cool, take the test. If you'd rather get paid for the gene pool you own, good luck.
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 %.
Yup, unless there’s a pill, people don’t want to take the effort before it’s already too late. It’s probably a reason why there’s such a bias towards medicine, even over basic stuff like healthy eating.
A good documentary on that subject was The Magic Pill. Well worth a watch!
Diet and exercise being by far the most important and lowest hanging fruit here is definitely true. But even so, what percentage of people do you think even have a rough idea of what an optimal diet+exercise routine would look like for themselves? Different fad diets have come in and out of fashion over the decades, and while some have had quite a bit of interesting research backing them, not all have.
Motivation is a difficult part, but I think we can help people out a lot by making accurate, personalized, and easily actionable information much more accessible to them.
There are metrics for weight at least for men that I’ve seen a common one is 2x body weight deadlift or squat. Find me a random person lifting that and I’ll show you a generally fit individual.
up to interpretation what easily means. We can definitely make things simple (easy to comprehend for uneducated and/or lower iq). But "easy" seems to be expressed by compliance and that seems to be the trick.
it's simple to not eat (ie fast) one day a week. it's simple to lace up your shoes and go for 30 minutes run. Yet neither of those are "easy" to get someone to do
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.
Unpublished data, I'm afraid, from a collaborator. But the manuscript is very close to submission. I'd expect to see it in 3-6 months.
It is honestly very hard to know about this kind of thing, because the results can vary based on how the analysis is done. But there is a severe publication bias effect in the sense that authors who see the clock giving a less than clean "story" tend to double and triple check their work and ultimately rarely to publish.
I have seen data going both ways on clock-disease associations, published and unpublished, so I do not know what the truth is, only enough to caution HN readers that a robust clock-disease association should not be taken as established truth.
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?
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.
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
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.
22 comments
[ 3.0 ms ] story [ 57.6 ms ] threadThere's a lot of interesting people that work on minimizing their biological age (sometimes measuring it with simple blood metrics that correlate with youth, and other times with more advanced and speculative ones like DNA methylation tests), and it's definitely an important, neglecting, and upcoming area. The downside is that to do a good job of maximizing your health and lifespan like this, it takes a lot of work, time, money, and research. For that reason I'm hoping some startups in this area do some amazing work and really start to make the field of healthspan and lifespan optimization more mainstream and accessible.
Some related links for those interested: https://peterattiamd.com/podcast/ (one of my favorite podcasts focusing on optimizing health and longevity), https://levels.health (GCM/metabolic fitness tracking startup), https://old.reddit.com/r/longevity/ (subreddit with many interesting links on longevity), https://ouraring.com/ (detailed sleep tracking+optimization startup), https://www.zerofasting.com/ (app to help track+optimize+inform about fasting), https://michaellustgarten.com/ (another interesting Doctor that does a lot of work on optimizing blood markers and diet), https://hackernoon.com/im-32-and-spent-200k-on-biohacking-be... (a more eclectic but nonetheless interesting approach to many biomarker optimizations)
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.
[0] https://medcitynews.com/2020/08/blackstones-4-7b-acquisition...
In general there doesn't yet appear to be common significant gains that can be made from the DNA tests available. Sometimes you will be lucky and find you're at high risk of certain things, but the vast majority of the information won't help you much. You still need to eat and exercise well either way.
Until this changes, and we can actually do a decent job of offering personal recommendations based off of one's DNA, you're likely better off getting a lot of blood tests and working from there.
I think my key fear is that it gets used against me for healthcare coverage.
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 %.
A good documentary on that subject was The Magic Pill. Well worth a watch!
Motivation is a difficult part, but I think we can help people out a lot by making accurate, personalized, and easily actionable information much more accessible to them.
up to interpretation what easily means. We can definitely make things simple (easy to comprehend for uneducated and/or lower iq). But "easy" seems to be expressed by compliance and that seems to be the trick.
it's simple to not eat (ie fast) one day a week. it's simple to lace up your shoes and go for 30 minutes run. Yet neither of those are "easy" to get someone to do
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.
It is honestly very hard to know about this kind of thing, because the results can vary based on how the analysis is done. But there is a severe publication bias effect in the sense that authors who see the clock giving a less than clean "story" tend to double and triple check their work and ultimately rarely to publish.
I have seen data going both ways on clock-disease associations, published and unpublished, so I do not know what the truth is, only enough to caution HN readers that a robust clock-disease association should not be taken as established truth.
- 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 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.