
Longevity Linked to Proteins That Calm Overexcited Neurons - tiagom87
https://www.quantamagazine.org/longevity-linked-to-proteins-that-calm-overexcited-neurons-20191126/
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ghostcluster
> In their new study, Yankner and his colleagues report that the brains of
> long-lived humans have unusually low levels of proteins involved in
> excitation, at least in comparison with the brains of people who died much
> younger. This finding suggests that the exceptionally old people probably
> had less neural firing. To investigate this association in more detail,
> Yankner’s team turned to C. elegans. They compared neural activity in the
> splendidly long-lived daf-2 mutants with that of normal worms and saw that
> firing levels in the daf-2 animals were indeed very different.

> “They were almost silent. They had very low neural activity compared to
> normal worms,” Yankner said, noting that neural activity usually increases
> with age in worms. “This was very interesting, and sort of parallels the
> gene expression pattern we saw in the extremely old humans.”

Does the low neural activity correlate with a less _active_ experience of the
world? Are you experiencing your state with the mute button on? I'm no
neurosurgeon, but if this is the trade-off, perhaps living longer by using
this REST gene might result in a less rich, dynamic, and textured experience?
Might it mean living a life like this is less 'fun'?

~~~
agumonkey
Depends on the nature of activity. Pure stress will activate your brain but
experience is mostly degraded.

~~~
daeroth
What if stressful existance pushes for shorter lifespan with the effect of
quickening the turnover of generations.

So stressful environment would speed up the evolutionary iteration of
generations. While less stressful existance that has adopted to the
environment would persist longer.

~~~
Enginerrrd
This analogy happens in some animals for sure. At the zoo they place the
antelope near the cheetahs so that they breed more.

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rpmisms
Does this relate in any way to the anti-aging drug cocktail that we saw a few
months ago?

IIRC that one related to genetic aging markers, and stress can affect mitosis.

It seems like immortality has a lot of building blocks, and the research isn't
far enough to combine them yet.

~~~
redsymbol
Anyone have a link to that? Sounds interesting.

~~~
keenmaster
You should watch Joe Rogan speak with David Sinclair, who researches aging at
Harvard, about the latest developments in his field
[https://youtu.be/ZGLL77wYxe8](https://youtu.be/ZGLL77wYxe8)

Aside from multivitamins and idiosyncratic drugs, Sinclair takes the following
supplements every day:

\- Resveratrol – 1g in the morning (this is synergistic with NMN)

\- Nicotinamide Mononucleotide (NMN) – 1g in the morning

\- Metformin (prescription drug) – 1g in the evening – except on days when
exercising, since metformin reduces muscle growth after exercising

(As an aside, he also engages in intermittent fasting, to reduce his total
feeding hours. There’s a theory that intermittent fasting triggers a
beneficial stress response whereby your body becomes more “efficient” in a way
that prolongs life. Intermittent fasting has been shown to prolong lifespan in
mice. Interestingly, resveratrol is expressed in plants as a defense mechanism
akin to what intermittent fasting does in humans, and that’s one of the
supplements that Sinclair recommends.)

Sinclair is very careful not to recommend that cocktail for anyone, since
anti-aging research is still very preliminary. The relevant human trials are
underway. However, NMN in particular has had astonishing effects on mice. Mice
that took NMN lived significantly longer than other mice. Old mice that took
it ran for so long that the measuring device on their running wheel timed out,
because they weren’t expected to ever run that long.

In old age, the NMN mice were conspicuously stronger, had more hair, saw
better, and were more mentally intact. In short, NMN might reverse the
underlying epigenetic causes of aging. Sinclair subscribes to the information
theory of aging, where, over time, your epigenome accumulates damage and
errors, and protective mechanisms die out. It’s like scratches on an
overplayed analog vinyl disc which slowly declines in function and eventually
stops playing altogether. You lose a majority of your NAD+ as you get older
(NAD+ is fed by NMN), which is problematic because NAD+ feeds biological
mechanisms which mitigate informational damage. That’s why supplementing with
NMN is theorized to have anti-aging effects.

Sinclair wrote a great book synthesizing aging research if you want to read
more about it.
[https://www.amazon.com/dp/1501191977/ref=cm_sw_em_r_mt_awdo_...](https://www.amazon.com/dp/1501191977/ref=cm_sw_em_r_mt_awdo_CG04DbR0WP5WS)

~~~
moh_maya
Re reservatol:

The jury is out in terms of its efficacy, or lack thereof. [1,2]

[1] [https://www.health.harvard.edu/blog/resveratrol-the-hype-
con...](https://www.health.harvard.edu/blog/resveratrol-the-hype-
continues-201202034189)

[2] [https://www.health.harvard.edu/blog/diet-rich-resveratrol-
of...](https://www.health.harvard.edu/blog/diet-rich-resveratrol-offers-
health-boost-201405157153)

Re. David Sinclair [3]:

"Despite his enthusiasm, published scientific research has not yet
demonstrated the molecule works in humans as it does in mice. Sinclair,
however, has a considerable financial stake in his claims being proven
correct, and has lent his scientific prowess to commercializing possible life
extension products such as molecules known as “NAD boosters.”

His financial interests include being listed as an inventor on a patent
licensed to Elysium Health, a supplement company that sells a NAD booster in
pills for $60 a bottle. He’s also an investor in InsideTracker, the company
that he says measured his age."

[3] [https://khn.org/news/a-fountain-of-youth-pill-sure-if-
youre-...](https://khn.org/news/a-fountain-of-youth-pill-sure-if-youre-a-
mouse/)

~~~
keenmaster
Yep, resveratrol on its own doesn’t seem to do much, which is puzzling given
its effect on mice. That’s why I added Sinclair’s claim that it is a
synergistic part of his drug cocktail. Let’s hope NMN is different. As for
Elysium, Sinclair is not affiliated with them and he said he doesn’t make any
money off of supplement sales.

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hourislate
> The results may help explain the observation that some drugs used for
> epilepsy extend life span in lab animals.

It would be interesting to find out if CBD (seizure control, calming effect)
might be beneficial in increasing levels of REST and calming neural activity.

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allovernow
Purely speculating, but perhaps this would place a positive evolutionary
pressure on migraines, since they are associated with cortical spreading
depression[1] which globally decreases neuronal activity for up to days at a
time.

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Razengan
Could this be related to the generally shorter lifespans of males?

~~~
alexis_fr
Life expectancy was the same for both genders in 1900 (in Europe at least).

We’ve just made continually more progress for women than for men. Nowadays for
example: lots of research on female cancer (twice more funding than male
cancers, for the same incidence and mortality) and domestic violence, little
budgets on suicide. Lots of money for equality at work where women are fewer,
little money for boys massively dropping at school. Practically no help if you
are a man facing a male-specific issue, which is why a lot of them engage in
the army or in Daesh (depending which side they tilt towards), and practically
all killers you know are boys victims of harassment, absent father syndrome
and on the spectrum of autism, with no help from the social fabric.

Men live shorter not because it is nature, but because we’ve made less
progress for them.

~~~
adventured
There are some interesting challenges to your premise, even though some of it
very clearly plays a role in the gap.

There is a six year gap (81 vs 87 as of 2018-2019) between men and women in
Japan. Arguably none of that gap is properly explained by the issues you've
raised. The Japanese are the healthiest, longest living people of any large
cohort on the planet and yet the gap persists.

Further, roughly twice as many girls (50.5%) born in 2019 in Japan will live
to 90 as boys (26.5%).

None of that is explained by things like rates of cancer (low in Japan),
school drop-out rates, domestic violence, murder rates, prison, crime, work
equality, army / Daesh matters, or suicide rates. Japan's male suicide rate
for example is below that of the US, Finland and only a few points above
France.

Yet the life expectancy gap between men and women is smaller in the US than in
Japan, which makes little sense if your raised issues were the leading cause
agents.

~~~
keenmaster
There’s a theory that longevity is lower in men because they need to be
stronger in order to survive in a conflict. It’s a trade off. Physical
strength is the result of growth, but some of the same pathways for increased
growth are also theorized to be the root cause of aging. Note that this is
independent of strength training; it’s the ability to get stronger, rather
than actually getting stronger (among other related characteristics), that may
affect longevity. Your intuition that accidental death and smoking do not
explain the entirety of the gender gap in longevity is spot on. It’s not all
bad news for men though. If you manage to avoid obesity and diabetes, your
increased strength and bone density may impart greater quality of life in old
age, and that may be worth the 3 lost years at the end of life.
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034172/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034172/)

~~~
beenBoutIT
The big killer among modern elderly people is the massive muscle wasting that
accompanies most inpatient hospital procedures. Having a solid foundation of
muscle can insulate a person from the dreaded point of no return after which
it would be impossible to build one's body back after a procedure.

~~~
nradov
Even without being bedridden for days after an inpatient procedure, we have an
epidemic of frailty among elderly people. This commonly causes serious falls
and fractures, and after an incident like that most people fall into a rapid
downward spiral. As a matter of public health policy we should be prescribing
weight training and higher protein diets for elderly people.

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2Xheadpalm
“The flame that burns Twice as bright burns half as long.” ― Lao Tzu, Te Tao
Ching

~~~
lookACamel
Pretty sure that's from Blade Runner not Dao De Jing.

~~~
loco5niner
Why not both?

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asah
Yay! Responsible journalism that includes debunks of obvious theories. More
like this, please.

~~~
copperx
Is this the norm for Quanta Magazine? If so, I'll subscribe.

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hbarka
I’m suspicious of the bacronym REST. Was it created to push the idea? I’d
rather they coined a neutral acronym. This one reeks of marketing.

~~~
LegitShady
Everyone knows you come up with the cool acronym first and then figure out
what the letters mean to fit the cool acronym.

