
Scientists think the cell nucleolus may play an important role in aging - rbanffy
https://www.nytimes.com/2018/05/20/science/nucleolus-cells-aging.html
======
subcosmos
The effect that they observe makes sense, implicitly, but I struggle to see a
causal link here.

The nucleolus is the site of ribosome synthesis, and ribosomes are needed to
make proteins. Under caloric restriction, the growth pathways in the cell get
turned down, and protein translation is held back until resources become
available again. It makes sense that the cell would stop synthesizing
ribosomes, which are HUGE structures that take lots of energy to make.

So I would say that reduced protein translation is a hallmark of longevity,
and the methionine restriction experiments support that. The nucleolus getting
smaller is likely one of the many effects of this adaptation.

I agree with the author however that this is a great and easily-measured
microscopic phenotype. Perhaps this can lead to awesome assays of cellular
aging, and perhaps even drug screening for compounds that are rejuvenating.

------
reasonattlm
It is funny what does and does not catch the attention of the popular science
press. This really isn't all that important as an example of research. It is a
very incremental increment in exploring the connections related to cellular
housekeeping and stress responses. There really isn't anything that can be
done with this knowledge that couldn't be done already with the existing
knowledge of the ribosome.

This is an example of the broad, dominant class of aging research that is
purely investigative. Most research into the detailed mechanisms of
degenerative aging is very far removed from any thought of application, and it
is lucky happenstance when such an opportunity does arise.

Unfortunately, systems very closely tied to cellular housekeeping, or
responses to stress, or replication seem unlikely to result in the foundations
of truly effective therapies. We can look at calorie restriction or exercise,
both of which alter all of the above items quite profoundly and throughout the
body, to see the plausible benefits that might be attained through
manipulation of these fundamental aspect of cellular behavior. We can also
look at the past fifteen years of research into these mechanisms to see just
how slow and expensive it is to try to produce therapies to slow aging - there
is very little to show for all of the effort invested.

Searching for means to adjust metabolism to modestly slow aging is not a
winning strategy; the expected benefits are just not large enough. We must
find ways to add decades of vigorous life, not just a few few healthy years.

------
Tharkun
So another datapoint indicating that caloric restriction might be a good idea,
with a plausible sounding mechanism of action.

------
jatsign
Based on various stories that have popped up on HN in the last few years,
there seems to be a lot of things inside us that _might_ determine how long we
live...

~~~
nonbel
It's a fundamental problem with modern day medical research. Rational people
would start from the principle that "every x is correlated somehow to every y"
(in this case "every aspect of the human body and environment is related to
aging"). Now that aspect is taken care of, so rational people can proceed to
figuring out quantitative models of these relationships.

However, the current paradigm is to reward people who check for "significant
differences/correlations", which just means that they "discover" all these
non-zero correlations. Basically it is a huge waste of time and money but it
works really well to generate an endless series of breathless press releases.

~~~
cycrutchfield
Go ahead and knock yourself out. If you think “creating a quantitative model”
of senescence is easy for “rational people”, then go right ahead. Your Nobel
prize awaits.

~~~
nonbel
Well, I didn't study senescence but actually did do something similar.

It required training myself in math, programming, history of the topic, and
stats in addition to the normal grad school stuff (memorizing stuff for
classes, data collection, etc) which amounted to about 3 years of working
almost nonstop.

Turns out nobody cared, all they wanted to know is if there was a significant
difference between groups. My attempt caused me health, financial, and social
problems for literally an anti-reward so I would not recommend anyone try it.
I also don't believe anyone would get a nobel prize for that in the current
environment, they would be ignored or fought against because some holy cows
would need to be sacrificed.

EDIT: As a more concrete example. Look at the pushback against Tomasetti &
Vogelstein for daring to point out that there is a base rate of mutations per
cell division and accumulated mutations lead to cancer, so cancers arise more
often in tissues with more divisions. This is almost common sense, but people
cannot handle it for some reason:
[https://www.theatlantic.com/science/archive/2017/03/no-
cance...](https://www.theatlantic.com/science/archive/2017/03/no-cancer-isnt-
mostly-bad-luck/521049/)

~~~
toopsss
Yes there are some idiots that dismissed the tomasetti and vogelsteinn paper
due to it conflicting with their worldview, but they only got momentum because
the original paper really was crap from even a critical scientific POV. What’s
very ironic is that the problems with the paper seem to be the same things
you’re bitching about in your post. No one smart is criticizing the paper for
the “common sense” part, but because they actually tried to quantify it and
their method was quite flawed.

~~~
nonbel
What were the problems in that paper? The good stuff is that they were able to
come up with estimates for stem cell divisions and were able to see a
correlation with the cancer risk.

The bad stuff was the usual misinterpreting correlation coefficients and
p-values (this is standard, found in pretty much every paper) and that the
data is messy/incomplete. I mean, sure more people should be working on
figuring out the number of stem cell divisions by tissue and other nations
should collect data of the same quality as SEER...

If it was just another standard "smoking/sunlight/etc causes cancer" paper
with the same issues there would not have been this response. It even says so
in the atlantic, people think this information undermines their public health
campaigns:

>' _The paper triggered a hailstorm of criticism. Some scientists chastised
the methods. Why did they ignore common cancers like breast and prostate? Why
did they only focus on the U.S.? Others accused the duo of undermining public
health. Many personal choices, from quitting smoking to staying lean, can
dramatically reduce one’s risk of cancers, but why would you bother if you
read headlines saying that these diseases are “largely down to bad luck?” '_
[https://www.theatlantic.com/science/archive/2017/03/no-
cance...](https://www.theatlantic.com/science/archive/2017/03/no-cancer-isnt-
mostly-bad-luck/521049/)

------
ilaksh
I like the SENS explanation for aging because it is more comprehensive and
plausible to me. See [http://www.sens.org/](http://www.sens.org/)

"The fundamental drivers of degenerative aging lie in the biochemical and
cellular side-effects of essential metabolic processes in the body. ".
[http://www.sens.org/research/aging-as-weve-known-
it](http://www.sens.org/research/aging-as-weve-known-it)

------
combatentropy

      Nucleolus = ProteinFactoryFactory

~~~
subcosmos
It makes little models, of factories

------
indescions_2018
Really excited to see YC Bio longevity startups when they launch.

------
Roritharr
So will my new born become immortal or not? Do I have a chance?

~~~
ddorian43
I still fail to see why the scintist-god would give you/me immortality unless
we become their slaves ?

Just give it to Bill Gates and he can hook you up with enough cash?

~~~
melling
The need to head for the dystopian view is overwhelming?

Of course, with some effort we might simply figure out how to double our
lifespans to 160-200 years.

Albert Einstein, for example, could still be alive discussing physics with
Stephen Hawking.

~~~
jacquesm
Science advances with the death of prominent scientists who have become
obstacles to progress. I see no reason why Hawkings or Einsteins would be
exceptions to that rule.

~~~
MikkoFinell
Yeah we can at last make some more progress in science, now that we're finally
rid of Hawking.

~~~
jacquesm
You are entirely missing the point.

If Hawking and Einstein lived longer so would everybody else. And that would
mean that a younger generation of scientists would have to wait _much_ longer
before their ideas could be discussed without opposition from the established
elders who see their pet theories attacked by these uppity youngsters.

The quote is a riff on what Max Planck, himself an eminent scientist said on
the subject:

"Science advances one funeral at a time."

[https://en.wikiquote.org/wiki/Max_Planck](https://en.wikiquote.org/wiki/Max_Planck)

~~~
MikkoFinell
> And that would mean that a younger generation of scientists would have to
> wait much longer before their ideas could be discussed without opposition
> from the established elders who see their pet theories attacked by these
> uppity youngsters.

Okay I will accept that premise for the sake of the argument even though I
don't actually believe it's true.

Based on that you go on to conclude it's a good thing that scientists die, so
that science can keep advancing.

You're essentially faced with a trolley problem, where pulling the lever one
way will make everyone immortal at the cost of slowing down scientific
progress, but pulling it the other way will euthanize everyone in the world,
and euthanize the countless billions that might live in the future. Somehow
your morals (or whatever you call it) tell you that euthanizing everyone is
better than slowing down scientific progress. I disagree with you there.

Why not even try to solve the problem some other way than killing everyone? I
don't know, why not, say, create an off-world colony outside the reach of
those evil progress-impeding elders. Just throwing ideas out there.

Taking your logic to its limit, why not just kill every scientist after their
first paper is published? But I don't think you actually want that, so lets
hear your argument against my strawman.

~~~
magduf
I also don't believe it's true. The entire nature of science is that theories
are modified or discarded as new empirical evidence disproves them. This idea
that established immortal scientists would cling to proven-false theories
despite evidence from "uppity youngsters" just flies in the face of what
science is all about.

If he were talking about politics, he'd have a point, since there's a lot of
irrational dogma in that field.

Also, don't forget, if we can figure out how to eliminate aging, that also
means we'll eliminate many (maybe all) things that go along with biological
aging, such as the changes to the brain that cause older people to tend to be
less adaptable (which really is a bit of a stereotype and not all that true;
my 80 year old mother happily uses a laptop computer, smartphone, and tablet,
while 30 years ago she wouldn't have dreamed of being like this).

~~~
neuromantik8086
> If he were talking about politics,

You seem to be operating under the assumption that science is apolitical. As
someone who's worked in science, I can assure you that it is not. Many non-
scientists listen to popularizers like Neil deGrasse-Tyson and come to believe
in a very idealized model of how science operates when the de facto "nature of
science" is more akin to what Thomas Kuhn describes in "The Structure of
Scientific Revolutions". I really wish that NDT were a bit more forthcoming
about his own experiences in science, seeing as how he barely made it through
the grad school gauntlet himself. Ditto for Carl Sagan, who made a powerful
enemy in Harold Urey (I can't find a link right now, but iirc Urey basically
gave Carl a bomb of a recommendation letter that cost him a tenured position
Harvard and compelled him to "settle" for Cornell).

In my personal experience (as well as the experience of many, many others if
you dig deep enough into this), some scientists can be very egotistical to a
point where they take a challenge to their theories as a personal affront, and
will employ insanely Machiavellian tactics to suppress dissenting opinions
(i.e., senior researchers are the ones who hold the purse when the NIH makes
funding decisions).

~~~
magduf
Problems like this can be mitigated or solved with policies, such as limiting
tenure or forcing professors to move on after a certain term. We already do
this with some politicians. What you're describing is really a problem with
academia, not science in general. Corporations doing scientific work don't
have those problems (they have other ones though), for instance.

~~~
neuromantik8086
True- I guess I should have specified "science within academia".

------
jlebrech
I've reached my article limit so i'm going to die.

~~~
subcosmos
Try becoming "born again" in an incognito tab?

------
Angostura
To save you a click, the Thing in question is the nucleolus, which
manufacturers ribosomal RNA.

~~~
Spare_account
And for those wondering (because I was) 'nucleolus' is not a typo, it is
contained _within_ the nucleus.

~~~
magduf
I remembered _just_ enough of my high school biology to (barely) remember the
term nucleolus when I saw it here....

------
Density
The immortal boomer meme inches ever closer.

~~~
magduf
First, Boomers will probably be mostly dead before all this anti-aging
research can benefit them.

Second, even if that's not the case, people are constantly getting killed off
thanks to our addiction to the automobile (and in America, the gun).
Eventually these Boomers are going to get knocked off. Maybe if we restrict
guns and get better public transit the Boomers can live for centuries, but I
don't foresee this; these changes are going to take centuries.

Edit: "addiction", not "addition"

~~~
perl4ever
I feel like I've read similar comments on HN about cars and guns over and
over. Seems odd to be preoccupied with cars and guns when most people don't
die of either. What about chainsaws and bathtubs? Cigarettes, trampolines,
etc?

Pneumonia, heart disease, stroke, COPD, pneumonia and lung cancer each kill
more than cars in the first world.

In the third world, top causes of death are HIV, pneumonia, heart disease,
diarrhea, stroke, malaria, TB, COPD, and measles - cars don't even make the
top ten.

Source:
[https://en.wikipedia.org/wiki/List_of_causes_of_death_by_rat...](https://en.wikipedia.org/wiki/List_of_causes_of_death_by_rate)

~~~
magduf
>I feel like I've read similar comments on HN about cars and guns over and
over. Seems odd to be preoccupied with cars and guns when most people don't
die of either.

Cars are the #1 killer for people less than middle-aged (where age-related
diseases take over). 30,000 people a year die in the US alone from cars, and
it's even worse in other countries.

>Pneumonia, heart disease, stroke, COPD, pneumonia and lung cancer each kill
more than cars in the first world.

Only for old people. For young people, the ones who really matter more for the
future of society and the economy, cars are easily the #1 killer.

Here's a source: [https://www.everydayhealth.com/kids-health/car-crashes-
the-n...](https://www.everydayhealth.com/kids-health/car-crashes-the-number-
one-killer-of-us-children-6504.aspx)

Guns are probably the #2 killer of children.

~~~
perl4ever
I agree that cars and guns are common causes of mortality among groups that
already have low overall mortality.

It occurred to me to look up statistics adjusted by years of life lost, which
gives more weight to younger victims and seems to favor your agenda.

From
[https://en.wikipedia.org/wiki/Years_of_potential_life_lost](https://en.wikipedia.org/wiki/Years_of_potential_life_lost)

"While the most common cause of death of young people aged 5 to 40 is injury
and poisoning in the developed world, because relatively few young people die,
the principal causes of lost years remain cardiovascular disease and
cancer.[4]"

[Regarding Australia:] "When disability adjusted life years are considered,
cancer (25.1/1,000), cardiovascular disease (23.8/1,000), mental health issues
(17.6/1,000), neurological disorders (15.7/1,000), chronic respiratory disease
(9.4/1,000) and diabetes (7.2/1,000) are the main causes of good years of
expected life lost to disease or premature death.[7]"

