
A genomic predictor of lifespan in vertebrates - Vaslo
https://www.nature.com/articles/s41598-019-54447-w
======
mullingitover
> In the past 200 years, the average life expectancy of humans has more than
> doubled because of modern medicine and changes in lifestyle

I thought this idea that humans had short lifespans historically was
thoroughly debunked. Humans have historically had high infant mortality rates
which threw the numbers off, but if you survived past the age of three you
were pretty likely to make it to your sixties or seventies.

~~~
philipkglass
It's true that infant mortality has decreased faster than other mortality in
the past century. Even people who survived past infancy had significantly
higher mortality rates at the beginning of the 20th century, though.

See "Table 6 - Period Life Tables for the Social Security Area by Calendar
Year and Sex" for detailed information from the United States:

[https://www.ssa.gov/oact/NOTES/pdf_studies/study120.pdf](https://www.ssa.gov/oact/NOTES/pdf_studies/study120.pdf)

In the table series for 1900, male life expectancy at birth was 46.4 years and
female life expectancy was 49 years. For the survivors of infant mortality,
additional life expectancy at age 6 was 53.2 years and 54.3 years
respectively. Most children could not expect to reach their 60th birthday even
if they had survived infancy.

At age 18, remaining life expectancy was 41.7 and 42.9 years, for total
expected age at death of 59.7 and 60.9 years respectively; weighted by sex
distribution at age 18, these young adults had an average life expectancy of
60.3 years.

~~~
ColanR
I don't think that looking at lifespans for the industrial revolution has any
bearing on what lifespans used to be 'historically'. It was pretty clear to
me, from reading the GP that they were talking about pre-industrial revolution
times.

~~~
philipkglass
Remaining life expectancy at age 18 was even lower in 1800 or 1700, from what
I can tell. You can find small exceptions (like aristocrats in particular
countries) but I'm not aware of any large (50,000 people or more)
preindustrial population where the average teenager could expect to die older
than age 60. I would be delighted to see counterexamples.

EDIT: This was interesting.

"Lifespans of the European Elite, 800–1800". It examines the lifespans of
European aristocrats over the thousand years prior to the Industrial
Revolution. It limits its analysis to people who reached at least 20 years of
age. Per Figure 8, the average lifespan remained below 60 in the entire time
period.

[https://www.cambridge.org/core/journals/journal-of-
economic-...](https://www.cambridge.org/core/journals/journal-of-economic-
history/article/lifespans-of-the-european-
elite-8001800/BE252C4B25C4AAC29ED62D591A1675AC/core-reader)

~~~
andai
I wonder what pre-agricultural lifespans were like? I read recently that
humans were significantly taller and healthier before agriculture, due to
getting nutrition from many sources rather than a few crops. I expect they
were much lower than in the cities, despite the nutritional advantage.

~~~
JumpCrisscross
> _pre-agricultural lifespans_

Probably short. Putting aside predation, disease and starvation, there is
evidence (see Pinker) that violent death was a common way to go in nomadic
tribes.

~~~
chrisweekly
Violent death was common, sure, but not necessarily more so in pre-
agricultural times. See e.g. the early chapters of "Sapiens" (Yuval Harari).
Agricultural revolution led to lower standard of living, increased risk of
starvation (feast-or-famine dependence on fragile harvest), increased health
issues (less-varied diet, also disease rampant in denser populations), and
whereas in the presence of potentially hostile competition nomadic hunter-
gatherers could choose to move, farmers would logically choose to stay and
fight rather than leave the farm and almost certainly die. The agricultural
revolution was a pretty bad deal for most people for most of the time since it
began.

~~~
littlestymaar
> See e.g. the early chapters of "Sapiens" (Yuval Harari).

This part of Harari's book have been debunked quite a few times already: his
views of pre-agricultural are romanticized and doesn't match with the work of
the specialists of this period. (While Harari is indeed an historian, he's a
specialist of medieval times and has little authority on early-humans
history).

Btw, I'm not even disagreing with you about agriculture, I just wanted to
point out that quoting Harari on that has really little value.

~~~
chrisweekly
Thanks, @littlestymar. To me, Harari's take seems more neutral than
"romanticized". I share his skepticism of those who claim concrete knowledge
of aspects of pre-literate human culture at which, logically, one can only
guess or imagine. This might counter your point about his relative expertise /
authority for that time period.

That said, I'm no historian, just a layperson who found Harari's work (so far
-- I haven't yet finished "Sapiens") thought-provoking and interesting. In the
relevant early chapters his perspective is refreshingly different from the
norm -- in some ways comparable (for me) to Zinn's "A People's History of the
US", in that it provides a PoV sufficiently removed from the standard
narrative to serve as a reminder of how shallow and incomplete any one-sided
version of events must be. The GP's citing of Pinker likely belongs in this
camp, too: referencing an author whose ideas have merit (eg Pinker's
computational theory in "How the Mind Works"), independent of their ultimate
status as authoritative works.

------
iten
I recently completed my PhD in vertebrate comparative genomics so this is fun
to see.

The single most important factor that needs to be accounted for in analyses
like these is the correlation between phylogenetic similarity and the trait in
question. In short, closely related species will tend to have similar
lifespans, _and_ closely related species will tend to have similar CpG density
in any fixed genomic region. So the fact that you can predict lifespan from
CpG density with enough parameters is unsurprising. You could almost certainly
predict lifespan fairly well from _any_ feature measuring phylogenetic
similarity -- I would have liked to see some evidence showing that CpG density
in these promoters is somehow uniquely suited for the task.

~~~
rflrob
I wonder whether they also looked at body size. Larger species tend to live
longer, so it could just be that their regions are just associated with
growth.

~~~
asdff
They did not.

------
derefr
So, is this suggesting that humans, as an animal species, are basically
"engineered" by evolution to have a 38-year flat part of their MTBF bathtub-
curve?

Where I mean "engineered" in the sense that evolution only can only really
steer toward adaptive fitness of an organism up until a certain point in its
lifetime, that being the point when the organism has done all the breeding
they're going to do. Past that point, most things the organism does won't
impact the evolutionary cohort of its species, so, turning that around, there
will be no adaptations in its genome to help it survive past that point
(since, where would they be sourced from?)

That time coming at 38 years for humans would explain a lot, I think. (It
makes sense; that's about the oldest average age that humans are willing to
continue to have children at.)

~~~
landryraccoon
Wouldn't evolution steer animals even after breeding if the parents continue
to contribute to the success of their children?

If having long lived parents was beneficial to their offspring, evolution will
select for longevity well past breeding age. OTOH, if an organism laid eggs
and then vanished from it's offspring's lives forever, then it would be hard
to see how evolution would select for longevity past the egg laying phase.

~~~
wahern
You're only 1/4 related to grand children. A strategy of living a long life to
help raise a grandchild means that 3/4 of your effort is promoting someone
else's genes. Now what if the strategy of those other people is to have many
more children, possibly with many different partners, with a relatively
diminished per-child investment, reliant on someone like _you_ to help raise
those children. Who's going to out-compete whom?

I'm not saying the second strategy is _better_ , just pointing out that the
first strategy is self-limiting. Which means we can't even begin to understand
the benefits and viability without answering more complex questions; questions
we don't yet have answers to.

Also, humans are the _only_ known species, extant or extinct, which exhibits
significant non-kin altruism.[1] There's no strong theory for how this
emerged. Which means there are some very important dynamics to human evolution
(and evolution in general) that we're completely ignorant to--we don't even
know what the questions are, let alone the answers.

[1] The most popular mammals used for comparison to humans, bonobos and naked
mole rates, are organized as matriarchies--the females are sisters, somewhat
like ants and bees. The above-average altruism they exhibit is easily
explained by basic Darwinian genetic evolutionary theory.

~~~
strbean
> You're only 1/4 related to grand children. A strategy of living a long life
> to help raise a grandchild means that 3/4 of your effort is promoting
> someone else's genes.

But you are helping to raise 100% of your descendants. I'm not sure it is
relevant that your descendants have less genetic material in common with you
as you move down the tree.

> Now what if the strategy of those other people is to have many more
> children, possibly with many different partners, with a relatively
> diminished per-child investment, reliant on someone like you to help raise
> those children. Who's going to out-compete whom?

The premise of Idiocracy! In this scenario, though, there could still be
benefits of _some_ per-descendant investment. I'm not sure "high investment in
few offspring vs. low investment in many offspring" debate really matters to
the question of "why stay alive longer than (age of infertility)+(maturation
time of offspring)".

I think the answers lie in 'group selection'. Not sure how accepted a theory
that is though. An example I've heard (but can't find reference to now) is
that the tonsils may serve to kill off sick individuals before they can infect
others.

------
ksydbd_383838
At a high level, I am very skeptical. Usually when your model does not agree
with observations, the problem is with the model. A few things that stand out
to me. I have not thought deeply about any of them, so please correct me if I
am mistaken about any of these.

> This primary data set contained 252 species from five vertebrate classes
> [...] We removed humans (Homo sapiens) from the data set as they were listed
> with a maximum lifespan of 120 years, which does not reflect the variability
> and the true global average lifespan (60.9–86.3 years)

So why should we trust the rest of this dataset? Garbage in garbage (GIGO) out
comes to mind.

> We used promoter sequences centred around the transcription start site (TSS)
> (-499 to 100 bp of each promoter) in Humans (Homo sapiens) from the EPD as
> the data set of promoter sequences. [...] Briefly, as described previously,
> using Basic Local Alignment Search Tool (BLAST) v2.2.31 the promoter
> sequences were mapped to the single top hit in each species.

This would seem to imply a weird correlation structure between data examples
that could pose problems for training/test split and/or linear models. I would
also liked to see some QC where they show how well this recovered known (i.e.
annotated) promoter regions. Are they picking up false positives? Are they
missing stuff?

> The glmnet function was set to a 10-fold cross validation which returns the
> best performing model. [...] This resulted in a total of 42 promoters for
> estimate lifespan.

So they're doing post-selection inference, so p-values are suspect. Tibshirani
(inventor of Lasso) and Taylor recently released a package for post-selection
inference, which I do not see them using here.

> Species were randomly assigned to either a training (176 samples) or testing
> (76 samples) data set (70/30 split).

Rule of thumb: you usually want about number of example = 10x number of
features to avoid overfitting. 42 features seems kind of thin. Even worse when
you consider that there might be a correlation between training and test
examples imposed by the initial selection of promoter sites using BLAST.

~~~
ramblenode
> > We used promoter sequences centred around the transcription start site
> (TSS) (-499 to 100 bp of each promoter) in Humans (Homo sapiens) from the
> EPD as the data set of promoter sequences. [...] Briefly, as described
> previously, using Basic Local Alignment Search Tool (BLAST) v2.2.31 the
> promoter sequences were mapped to the single top hit in each species.

Measurement error should probably be modeled.

------
valw
To the experienced data scientists / statisticians here: does this sort of
regression analysis between the actual and predicted age seem legit to you?

It seems very weird to me. From what I understand, the p-value tests the
hypothesis that the predicted and actual data are correlated, which seems like
a very weak way of assessing the reliability of the prediction.

An estimator of the test error seems more relevant, and that's kind of what
the R^2 does, but why do an affine regression between predicted and actual
value instead of say an RMS error? Isn't this using the test data for
parameter-fitting, i.e training?

------
shele
If the “natural lifespan” of humans ends to be 38 you are using a flawed
definition of natural. This also connects to people believe that humans in the
past died with 30 latest because the life expectancy was 26 years, ignoring
that this is an average heavily influenced by child mortality

------
krustyburger
> Early humans have been reported to have a maximum life expectancy of 40
> years, less than half by modern standards. Similarly, in chimpanzees the
> lifespan was estimated at 39.7 years. The maximum longevity of a chimpanzee
> in the wild is thought to be of a 55 years old female, however it is
> reported that many live to approximately 40 years of age.

It seems like what we’re really seeing here is the similarity in lifespan
between our earliest human ancestors and other primate species.

The earliest humans would not yet have had access to consistent shelter, fire
or tools/weapons and these developments carried with them enormous benefits
with respect to health and comfort.

------
ColanR
Off topic, but based on the discussions here.

I'm seeing a lot of discussion here about how the lifespan of humans (not
counting infant and teen mortality rates) may not have improved much in the
last thousand years. As a tangential question, does that mean all our medical
progress has a) improved infant mortality and b) counteracted the
unhealthiness of modern life, and not done much for us beyond that?

~~~
lordnacho
From what I've read that's right. Kids don't die on nearly the same scale,
likewise mothers giving birth.

Nutrition has gotten better, which helps immune system strength.

We know what causes a lot of diseases and can protect against their spread.
Both reactively in terms of illnesses people get and in terms of prevention
such as vaccines and warnings about smoking.

Even then there are records of famous ancient people like Egyptian kings who
lived to what we'd still consider a ripe old age now.

------
jmpman
No comments about dog lifespans? Come on genetic engineering, give me a
Labrador that lives 20 years and doesn’t shed.

~~~
asdff
Get a hairless cat, similar personality actually

------
hprotagonist
previously
[https://news.ycombinator.com/item?id=21773562](https://news.ycombinator.com/item?id=21773562)

------
raspasov
Can we please repeal and replace the title of this with “A genomic predictor
of lifespan in vertebrates” (aka the real title) ?

~~~
dang
Yes. The submitted title was "Humans have a natural lifespan of only 38
years", which broke the site guidelines. They ask: " _Please use the original
title, unless it is misleading or linkbait; don 't editorialize._" We've
reverted the title now.

[https://news.ycombinator.com/newsguidelines.html](https://news.ycombinator.com/newsguidelines.html)

~~~
raspasov
_thumbs up_

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tpmx
That article title is crap.

Edit: the title is fixed now.

~~~
alexgmcm
I agree, that title is awful given the actual link.

