
Study of over 1m people finds association between lifespan and blood iron levels - bookofjoe
https://www.nature.com/articles/s41467-020-17312-3
======
viburnum
For those of us who aren't in the life sciences, is this saying too much iron
is good or bad?

~~~
dnautics
I think the article says iron levels are negatively correlated to longevity,
but "the association might be due to a already-known correlation to
haemochromatosis" which I have no idea what that is. I presume it's some known
population that's old that happens to also have an enrichment of
haemochromatosis but where individuals in that population without it do not
show a positive defect in longevity?

Edit: specified as negatively correlated

~~~
agsacct
Due to them saying that "the association might be due to an already-known
correlation to haemochromatosis" I'm assuming they didn't have the data to
correlate haemochromatosis to the data.

Haemochromatosis is a genetic disorder where individuals are unable to get rid
of excess iron. If properly diagnosed, this is easily treatable with
bloodletting (blood donation in this century :-)

Haemochromatosis is the sort of genetic disease that could really screw with
data like this. Undiagnosed haemocromatosis leads to early death....so the
correlation of excess iron to longevity should be treated as a weak piece of
evidence until we can exclude people with the genetic disorder.

~~~
paulrhjtimmers
Great comment! For the iron - ageing link, we used two pieces of data: the
effect of DNA on blood iron levels, and the effect of DNA on how long and
healthy you live. We found the mutation that causes hereditary
haemochromatosis had a large effect on early death (as expected). However,
other genetic variations that increased blood iron levels also had a
proportional effect on early death. So it looks like it is higher iron levels,
not just haemochromatosis, that may accelerate the rate of ageing.

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alexnewman
How did they remove the correlation with sex? Did they control for the females
living longer and having lower blood iron levels

~~~
cauthon
If only there were a section of scientific papers devoted to explaining the
Methods used to obtain the Results. It’d be especially great if it came after
an Introduction explaining the context and was followed by a Discussion of the
merits, weaknesses, and impact of the study.

~~~
CodeAndCuffs
Hey friend. You're 100% right for pointing out that this stuff is addressed in
the paper. I think the sarcasm is a disservice to everyone, both you and the
parent comment included. Further, he may not have had (or may not have) the
time to fully analyze the paper, and may be asking if others are aware if that
specific concern is addressed, which seems like a reasonable comment.

~~~
enraged_camel
Sorry, I don't really agree. HN is full of people who react to headlines
without reading the article and the underlying materials, and in my opinion it
greatly decreases the quality of discussion.

~~~
totetsu
I was reading ..somewhere.. that a person having a negative interaction on an
online forum increased the likelihood of that person then going on to make a
negative comment themselves 300%. When I read that HN's zealous downvotes of
slightly impolite comments started to make a bit more sense to me. It's better
to avoid snark and sarcasm, as fun as they are.

~~~
vaxman
If your life revolves around acceptance by HN mods, then you need to wakeup
from The Matrix!

Nobody wants another cesspool like /. was in its hay day, but ultimately only
HackerNews/Ycombinator are harmed by this phenom of over-moderation.

For example, whose brilliant idea was it to create a user community that
downvotes on comments hostile to Chinese Communist Party (that aims nuclear
weapons at us while supporting North Korea in every sense and planning to kill
our trading partners in Hong Kong and Taiwan) or on comments brutally critical
of Apple for abusive trade practices? A lot of the downvotes also come from
users that are obviously very inexperienced and unable to understand subtle
contexts leading one to believe that a great way to solve this “problem” would
be to only allow moderation by senior members of the community, as determined
by peer votes, not by account age.

~~~
totetsu
Isn't 500 karma needed to downvote? Karma might be an indicator of seniority
indicated by peer vote. As for the other issues, there are ways of being
highly critical without needing to be brutal.

~~~
vaxman
"peers" lol

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chr1
So if iron accumulation is bad does that mean the medieval doctors with their
bloodletting were on to something after all?

~~~
throwayws
Blood donations are the modern positive equivalent.

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gerdesj
Rubbish HN article title. The Abstract and Intro in the article do not mention
the word iron at all.

Later on we get: "Mendelian randomisation of iron traits" and the HN title
looks very suspect. The sort of cobblers a supplement pusher might write.

~~~
bookofjoe
>Haem Definition and Examples - Biology Online Dictionary

>What does haem mean in biology?

haem. 1. (Science: biochemistry) compounds of iron complexed in a porphyrin
(tetrapyrrole) ring that differ in side chain composition.

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elliekelly
> Twenty one of the 24 multivariate GWAS loci reaching genome-wide
> significance had directionally consistent effects in the three studied
> datasets and 18 were nominally significant (P < 0.05) in two or more
> datasets (Supplementary Fig. 1).

Unrelated to the content of article but why are “twenty one” and “three” and
“two” spelled out but 24 and 18 are written as numerals? Is there any rhyme or
reason to this? I find this kind of inconsistency so distracting when reading
technical papers. It makes me think some of the numbers were edited/changed
last-minute in subsequent drafts.

~~~
vharuck
Style guide. Sounds like the one my work uses (Associated Press):

\- Numbers up to ten are written as words

\- Numbers 11 and higher are numerals

\- Any number that starts a sentence is written as a word

~~~
flowerlad
What does your style guide say about periods? I notice none of your bullets
ended with a period. As a programmer I often struggle with whether I should
end my comment with a period.

~~~
vharuck
First, I dislike the AP style guide. So my own writing will sometimes violate
it just to please me.

As for periods, any phrase that is a complete sentence must have a final
punctuation mark. So my bullet points would've required periods in a report.
They also could've been connected by semicolons with a conjuction at the end
of the second-to-last point:

\- A;

\- B; or

\- C.

The idea is to stick to proper English sentences. The bullet points are just
incidental formatting.

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Munky-Necan
> The effects of loci of interest on male and female lifespan are largely the
> same, although their effect on survival may be slightly stronger in middle
> age (40–60 years) compared to old age (>80 years).

This is interesting. I have a feeling that because there are many congenital
cardiovascular and other congenital diseases that one usually succumbs to in
the 40-60 range that is what we are seeing a stronger link to genes here.
Unless a parents passes away before the age of 55 from a heart attack it's not
considered hereditary.

I find it interesting when studied like this are performed. One of the best
predictors of life expectancy in elderly individuals is grip strength; not
because of the fact that one has a strong grip, but because a stronger grip
means more muscle mass leading to longer life. When I see that iron levels are
correlated to longer lifespans I wonder if there's something else going on.
Many women, in particular, walk around with iron deficient anemia and don't
realize their fatigue is because of their lack of iron. Anyway, I'm excited
for this line of research to be further delineated.

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dkural
from the article: "Interestingly, protective variants near FOXO3 are
associated with a reduction in metabolic syndrome, but also with a reduction
in cognitive ability."

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aristophenes
Is this what is called “p hacking”? Looking a among many different criteria
until you find one that is statistically significant?

~~~
ImaCake
This is a good question to ask and I am not sure why you are being downvoted.
The answer is that p-hacking was a real problem back when these kind of large
multi-gene frequency analysis studies were just starting out. Not
intentionally, mind you, just that the people running the studies were
biolgists first, and statisticians only on an ad hoc basis. In the late 90s
and early 2000s there was a lot of debate about the poor quality of
statistical analysis in the field and things started to improve. Today these
studies have a bunch of descriptivist and bayesian tools they can use to sort
out real positives and negatives from false ones. The result is that these
studies now discover real and important genes that impact complex diseases. We
are finally getting close to the dream of personalised medicine.

A good further read is the 1998 paper that describes the problem in detail:
[http://ib.berkeley.edu/labs/slatkin/popgenjclub/pdf/terwilli...](http://ib.berkeley.edu/labs/slatkin/popgenjclub/pdf/terwilliger-
weiss1998.pdf)

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sdinsn
Misleading title. Mention of blood levels are few, and the authors say it's
uncertain and needs further research anyway...

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m_a_g
For these kinds of articles, it is important to remember that correlation does
not imply causation.

~~~
whoisjuan
People say this so much that is now used as a way to dismiss any study. It’s
almost becoming a meme.

I think is clear that the baseline of any study is that correlation does not
imply causation. You start there. That’s a basic intelligent start. You never
take for granted that one thing causes the other. The ideas is to try to
identify if there are any potential paths for causation.

Otherwise there’s not even a point in sharing or discussing these studies.

I’m not saying that bringing this up is wrong, but does it need to be said so
much? I think it’s more interesting to analyze beyond that and try to see if
there’s causation. We already know there’s an abysmal amount of correlated
things but there must be a percentage of those things which are in fact caused
by another at a certain level. I would love these discussions to be more
focused on this and not just doing the plain classic dismissal of “correlation
doesn’t mean causation”.

~~~
23B1
It needs to be said so much because people weaponize scientific studies in the
pursuit of their political agenda, media twist headlines to get clicks, etc.
I've lost track of the number of articles that bury the "the authors of the
study caution against any definitive conclusion about causation/correlation"

~~~
rimjongun
If the goal is rhetoric and not truth, no amount of repeating droll truisms is
going to prevent that. Additionally this comment thread has been fairly tame.

It doesn’t need to be said so much, obviously. I’ve counted what, 3 times so
far in just this thread?

It doesn’t make you sound smarter.

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deeblering4
Is there a TL;DR version of what to take away from this article?

I read it, but didn’t understand what the conclusion is, or if it’s actionable
or not. Should I better monitor my iron intake or something?

~~~
Mathnerd314
The tl;dr is they found some genes relating to iron metabolism and other key
cellular processes that are correlated with longevity and healthy ageing. It
doesn't seem particularly actionable unless you're a DNA researcher.

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nicc
Someone wants to sell his supplements, uh?

Title is: "Multivariate genomic scan implicates novel loci and haem metabolism
in human ageing".

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1996
Longevity (lifespan) is only part of the picture.

Frailty is another metric, probably more important as you want to live a long
live while being able to use your days.

~~~
DavidChouinard
The authors explicitly address this point, calling it "healthspan".

~~~
1996
They say they do, but I'd say they didn't do that properly.

Quoting the relevant part for you that lead me to this conclusion:

> "For one, there are currently no widely accepted standards for measuring
> healthspan. Zenin et al. define healthspan based on the incidence of the
> eight most common diseases increasing exponentially in incidence with age in
> their sample. "

> "Recent estimates suggest the genetic components of both human lifespan
> (i.e. the number of years lived) and healthspan (the number of years lived
> in good health free of morbidities) are only around 10%"

> "Parental lifespan correlates strongly with both healthspan (rg = 0.70; SE =
> 0.04) and longevity (rg = 0.81; SE = 0.08), while healthspan and longevity
> show a weaker correlation with each other (rg = 0.51; SE = 0.09)"

The authors may pretend they studied healthspan, but I'd rather say they
studied biased data (as death is well reported, while autonomy is harder to
asses according to their own words), on something poorly correlated with
healthspan, which even if we assume perfect correlation can only explain about
10% of the difference.

> healthspan correlated more strongly with metabolic traits (such as type 2
> diabetes) than the other studies, and showed negative genetic correlations
> with depression and cancers, especially melanoma

So I would not call the article rubbish, but I would be careful to extrapolate
that iron matters so much:

> These correlation estimates ranged from 0.013 between healthspan and
> longevity to 0.094 between healthspan and parental lifespan, reflecting a
> small degree of sample overlap and/or phenotypic correlation

Indeed, parental lifespan may explain more! Even better, look at the
coefficient in table 3:

>
> [https://www.nature.com/articles/s41467-020-17312-3/tables/3](https://www.nature.com/articles/s41467-020-17312-3/tables/3)

βlongevity is 5x more than βhealthspan , and one coefficient even changes sign
(ferritin) possibly due to haemochromatosis (I'm too lazy to check, I've
already spent too much time on this article) so I wouldn't jump to conclusions

