Longevity Linked to Proteins That Calm Overexcited Neurons
quantamagazine.org
quantamagazine.org
> “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'?
So stressful environment would speed up the evolutionary iteration of generations. While less stressful existance that has adopted to the environment would persist longer.
It's also possible the association is in the other direction - people with neurons that fire less might be less stressed in general (almost by definition), and maybe the effect of stress on longevity takes place elsewhere entirely.
From the fine article:
> "Neuronal overactivity may not feel like anything in particular from the viewpoint of the worm, mouse or human, unless it gets bad enough to provoke seizures. But perhaps over time it may damage neurons."
No.
> It’s not yet clear from the study whether or how a person’s thoughts, personality, or behavior affect his or her longevity.
https://news.harvard.edu/gazette/story/2019/10/nervous-syste...
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.
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_...
He also gave the aforementioned drug cocktail to his elderly dad and said it seems to have rejuvenated him. His dad is hiking all around Australia, just like he did as a young man. I paid little attention to that particular claim since it is an n=1 anecdote.
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...
[2] https://www.health.harvard.edu/blog/diet-rich-resveratrol-of...
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://www.nature.com/articles/d41586-019-02638-w
This blog post has commentary on the study. If you are interested in the topic, consider suspending disbelief until after reading the post. It does a great job of clarifying what the evidence actually shows, and outlines one way to contextualize this intervention.
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.
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.
1: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsde...
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.
??? Not for Stomach cancer or CRC.
CRC: High in Japan vs most other countries, and significantly more prevalent with men: https://www.wcrf.org/dietandcancer/cancer-trends/colorectal-...
Stomach: https://www.wcrf.org/dietandcancer/cancer-trends/stomach-can... men get is almost 3x more than women in Japan and Japan is the top 3 worldwide in incidence.
And overall death rates by cancer for men in Japan are quite a lot higher than for females: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929724/figure/...
For suicides in Japan it's predominantly men who commit suicide, with a ratio of 2.53 vs female: https://en.wikipedia.org/wiki/List_of_countries_by_suicide_r...
Before making blanket statements you may want to check the data...
I'm personally of the hypothesis that in most cultures men undertake activities that end up killing them earlier in aggregate than women.
Probably because other factors that would kill early both men and women much sooner dominated. Like trying to measure the performance of a program when the disk is too slow and ending up measuring the disk...
- men smoked at higher rates than women
- men were more likely to drink heavily
- men were more likely to engage in dangerous work (construction vs nursing)
- men were more likely to drive aggressively and/or drive motorcycles
- men were far more likely to say "watch this!" and do something like, oh, jumping off the roof of a house an into a pool
So why do men have worse social support than women? First we can look at is how society reward men who focus their time on social networking compared to a focus on career and higher income. On average, how do society react if a man choose a high social job such as nursing vs a high income job such as construction, and then compare that average for women.
The second thing we can look at is a more obvious one. On average men are more likely to be childless than women. It should surprise no one that having one or more children does increase the probability of a social support network at old age.
The third thing is suicide which is the single largest cause of death for men until age of 65 (if I remember right). Suicide is highly correlated with untreated depression, a illness where it is well know that men is in the receive end of discrimination. Very few culture has any tolerance for men with mental illness, and this again is correlated to social support and in the long run stress management. Men with mental illness run higher risk of handling it alone compared to women.
It should be noted here that for the age groups where "drive aggressively and/or drive motorcycles" is relevant, suicide is still more common cause of death. I will also include the age groups of people who say "watch this".
In the article it says REST was studied previously in contexts that have nothing to do with aging.
At least it's not as overloaded as SAD.