Cognitive abilities are declining in zero gravity

[Cassel]

If this is true and the fact that telomeres are shorter after returning to Earth, then we can forget about traveling into space.

https://www.sciencenews.org/article/nasa-twins-study-reveals-effects-space-scott-kelly-health

Edited April 20, 2019 by Cassel

[MinimumSky5]

Telomeres: Yeah, fair enough, that had me worried too when I saw that. That being said, as his telomeres lengthened during his stay at the ISS, that hints that there is a way for adult, mature cells to lengthen their telomeres, and so there might be a pharmaceutical work around to this. Which would also, incidentally, be a potential game changer for geriatric medicine. 

Cognitive changes: remember that this is a guy on the sunset side of 55, so over one year he almost definatly would have a small but detectable decline in his cognitive abilities. 

[Bill Phil]

Well if I recall telomeres actually lengthen while in space, but then shrink once on Earth, possibly an adaptation to the free fall environment.

But that’s just it: all this science is only valid for free fall. If we used rotation to induce pseudo-gravity these issues could be dealt with, potentially completely, and shorter jaunts haven’t been problematic, at least for the hundreds who have been to space.

[kerbiloid]

Spoiler

Let me reaffirm the results of this study.

Every time after spending several holiday hours in KSP zero gravity, my cognitive abilities decline in the evening.

 

Edited April 20, 2019 by kerbiloid

[Cassel]

1 hour ago, MinimumSky5 said:

Cognitive changes: remember that this is a guy on the sunset side of 55, so over one year he almost definatly would have a small but detectable decline in his cognitive abilities. 

That's why they are studying twins?

[MinimumSky5]

48 minutes ago, Cassel said:

That's why they are studying twins?

Yeah, no, fair point there. 

As @Bill Phil pointed out though, centrifugal forces should mitigate these effects. 

[ThatGuyWithALongUsername]

5 hours ago, Cassel said:

If this is true and the fact that telomeres are shorter after returning to Earth, then we can forget about traveling into space.

That's a bit excessive. For shorter journeys, people are fine, and for longer journeys we can use a centrifuge as @Bill Philpointed out. There's so many other health problems with zero g to begin with anyway, this doesn't really change much. No need to cut off all space travel, that's just completely ridiculous.

[kerbiloid]

Spoiler

5 hours ago, Cassel said:

then we can forget about traveling into space.

Quote

Cognitive abilities are declining in zero gravity

Yes, a spaceman returns from the space and has absolutely forgotten that he had flied somewhere, due to the declined cognitive abilities.

He asks the ground team: "So, when I fly?"
Ground team: "??? Fly to where?"
Spaceman.: "What do you mean "where"? To space."
Ground team: "What space?!"
Spaceman.: "The space." 
Ground team: "Aren't you enough?"
Spaceman.: "Stop kidding me! I'm a spaceman, I need a space."
Ground team: "Space?! Of course, space. Please board this van, and it will deliver you to the place with space."

 

[YNM]

5 hours ago, Cassel said:

we can forget about traveling into space.

I already forgot about space travel - living in 3rd world country and whatnot...

 

... But if there's a will, there's a way. Surely you guys will figure something out...

[Cassel]

4 hours ago, MinimumSky5 said:

Yeah, no, fair point there. 

As @Bill Phil pointed out though, centrifugal forces should mitigate these effects. 

 

1 hour ago, ThatGuyWithALongUsername said:

That's a bit excessive. For shorter journeys, people are fine, and for longer journeys we can use a centrifuge as @Bill Philpointed out. There's so many other health problems with zero g to begin with anyway, this doesn't really change much. No need to cut off all space travel, that's just completely ridiculous.

 

48 minutes ago, YNM said:

I already forgot about space travel - living in 3rd world country and whatnot...

 

... But if there's a will, there's a way. Surely you guys will figure something out...

This is an interesting phenomenon, it has been discovered that something like this occurs, and you think that you already know how to solve this problem and what it is related to.

Can you show me where under the conditions 0g tested the impact of "centrifugal forces" on human?
How do you know that it is not related to food that astronauts take?
Or maybe with gravity, after all the fact that the Earth is rotating does not generate gravity force, the mass of the planet generates it.

[tater]

Seems like they should test a centrifuge in LEO, and work out if it's radiation or microgravity that is the culprit here.

[YNM]

1 hour ago, Cassel said:

This is an interesting phenomenon, it has been discovered that something like this occurs, and you think that you already know how to solve this problem and what it is related to.

As I said, it's your problem.

The rest of us is like the folks who were desperately clinging to earth in Interstellar, and I hope there's some Cooper family and NASA out there ready to give the breakthrough.

[Bill Phil]

2 hours ago, Cassel said:

 

 

This is an interesting phenomenon, it has been discovered that something like this occurs, and you think that you already know how to solve this problem and what it is related to.

Can you show me where under the conditions 0g tested the impact of "centrifugal forces" on human?
How do you know that it is not related to food that astronauts take?
Or maybe with gravity, after all the fact that the Earth is rotating does not generate gravity force, the mass of the planet generates it.

We already knew about problems in free fall, though.

We also know that centrifuges can provide a force very similar to the normal force we experience on Earth - we don’t feel gravity, we feel the normal force. According to relativity the pseudo force that people in accelerating frames experience is practically identical to the force people on Earth feel, though possibly with different magnitudes. Thus there’s reason to believe that a centrifuge can at the very least mitigate these issues if not completely fix them. There are other issues as well such as fluid flow differences in the body where a force like gravity would help tremendously.

Not to say I wouldn’t appreciate experiments that test this in space, of course.

If I recall the twin experiment did their best to keep almost everything except for the different environment the same, so food is an unlikely culprit.

Rotation doesn’t generate gravity, rather it forces objects to follow a curved path by accelerating them, but this acceleration is felt as “gravity.” 

1 hour ago, tater said:

Seems like they should test a centrifuge in LEO, and work out if it's radiation or microgravity that is the culprit here.

I don’t think radiation would be that significant. Maybe that’s an aspect for the telomeres, but I’m not sure about cognitive functions.

[wumpus]

9 hours ago, MinimumSky5 said:

Telomeres: Yeah, fair enough, that had me worried too when I saw that. That being said, as his telomeres lengthened during his stay at the ISS, that hints that there is a way for adult, mature cells to lengthen their telomeres, and so there might be a pharmaceutical work around to this. Which would also, incidentally, be a potential game changer for geriatric medicine. 

Cognitive changes: remember that this is a guy on the sunset side of 55, so over one year he almost definatly would have a small but detectable decline in his cognitive abilities. 

Cognitive changes: The US Navy is unlikely to publish data for similar results on board submarines.  I wonder what the results for Antarctic base (especially over the N. hemisphere's summer) are.

[KerikBalm]

On 4/20/2019 at 8:46 AM, MinimumSky5 said:

that hints that there is a way for adult, mature cells to lengthen their telomeres, and so there might be a pharmaceutical work around to this. Which would also, incidentally, be a potential game changer for geriatric medicine. 

Its called telomerase... and cancer cells often start making it...

No free lunch:

https://en.wikipedia.org/wiki/Telomerase_reverse_transcriptase#Role_in_cancer

[MinimumSky5]

But germ cell lines by definition must also produce it, so there is a regulatory system that can control telomerase and also prevent cancer. 

I'm not completely disagreeing though, given that ovarian and testicular tumours are quite common causes of cancer, but I don't buy that simply increasing the expression of telomerase would automatically lead to cancer. 

[KerikBalm]

11 hours ago, MinimumSky5 said:

I don't buy that simply increasing the expression of telomerase would automatically lead to cancer. 

It doesn't automatically lead to cancer, it is still associated with cancer.

To divide indefinitely, cells need to maintain their telomeres (cancer cells that don't express it use an alternate route to maintain telomere length). To become cancerous, cells must develop a way to grow without being given the signal to, ignore signals to stop growth, and maintain their telomere length. By stopping the production of telomerase, cells have a limited time to accumulate all the needed mutations. Extending telomeres extends the time the cell has to accumulate all the needed mutations.

Thus, indirectly, lengthening telomeres increases the chances of a cell becoming cancerous, simply because it has more time to become cancerous.

Luckily many mutations that lead to cancer also make an embryo non viable, so there's a lot of selection before one is born. Also, one has to keep in mind the total cell number. More cells means more chances for bad stuff to happen, so it makes sense that evolution would limit the number of cells that automatically maintain telomere length.

Quote

A comparative biology study of mammalian telomeres indicated that telomere length of some mammalian species correlates inversely, rather than directly, with lifespan, and concluded that the contribution of telomere length to lifespan is unresolved.^[30] Telomere shortening does not occur with age in some postmitotic tissues, such as in the rat brain.^[31] In humans, skeletal muscle telomere lengths remain stable from ages 23 –74.^[32] In baboon skeletal muscle, which consists of fully differentiated post-mitotic cells, less than 3% of myonuclei contain damaged telomeres and this percentage does not increase with age.^[33] Thus, telomere shortening does not appear to be a major factor in the aging of the differentiated cells of brain or skeletal muscle. In human liver, cholangiocytes and hepatocytes show no age-related telomere shortening.^[34] Another study found little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities.^[35]

Some experiments have raised questions on whether telomerase can be used as an anti-aging therapy, namely, the fact that mice with elevated levels of telomerase have higher cancer incidence and hence do not live longer. Telomerase also favors tumorogenesis, which leads to questions about its potential as an anti-aging therapy.^[36] On the other hand, one study showed that activating telomerase in cancer-resistant mice by overexpressing its catalytic subunit extended lifespan.^[37]

A study that focused on Ashkepedant Jews found that long-lived subjects inherited a hyperactive version of telomerase.

There is clearly potential, and the enzyme is known, but you don't want it to be delivered to cells with defective copies of oncogenes/tumor suppressor genes. If we were doing personalized medicine/ you had a very low incidence of cancer in your family, you may want telomerase in your somatic cells. If cells aren't dividing (or aren't dividing much), telomeres don't shorten. If the cell can clearly be recognized as being out of place, the immune system can kill it even if it would otherwise be cancerous (which is why cancer is usually not transmissible, except in cases where genetic diversity is very low, as in threatened species, or species that have been through a bottleneck: https://en.wikipedia.org/wiki/Canine_transmissible_venereal_tumor  https://en.wikipedia.org/wiki/Devil_facial_tumour_disease) this may be why testicular cancer is not sooo common.

But I can virtually guarantee that if a drug were to come out, that wasn't carefully controlled (starting with genetic testing), it would increase the cancer incidence in those taking it, and it would be pulled from the market.

For my master's project, I made a series of viruses which had a viral promoter replaced with the human hTERT promoter. Thus if the cell was not making transcription factors that would transcribe the hTERT gene in the cell, the viral genes would not be transcribed either (and the transcription factor that the virus encoded doesn't work with its own promoter). Thus the virus would not replicate in most somatic cells. Of course, you don't want a virus that kills stem and germline cells either... so you replace another viral promoter with a human promoter that is active in differentiated cells (not stem cells)... in my case this was done by a master student before me, and the promoter was Tyrosine, which is highly active in melanoma cells (Tyrosinase: https://en.wikipedia.org/wiki/Tyrosinase ) and is involved in the production of melanin. Stem cells don't produce melanin, that is a marker of differentiated cells. On top of that, the Ad5 virus normally produces an anti-apoptotic protein to stop the cell from dying due to apoptosis (from an internal or external trigger in response to infection) - cancer cells already have defective apoptosis mechanisms... so the virus won't reproduce unless it finds cells with a defective apoptosis mechanism, that express high levels of tyrosinase (ie, make a lot of melanin), and high levels of telomerase... the idea was that any cell fitting those conditions would be cancerous (stem cells, even adult stem cells should have working apoptosis mechanisms, and shouldn't be producing tyrosinase until they've differentiated and stopped producing hTERT).

Of course... the project was purely academic... injecting live virus into people also faces an uphill battle against regulatory authorities... because of cases like this:

https://en.wikipedia.org/wiki/Jesse_Gelsinger as well as this one: https://en.wikipedia.org/wiki/X-linked_severe_combined_immunodeficiency#Treatments

Quote

In one particular trial by Cavazzana-Calvo et al., ten children were treated with gene therapy at infancy for X-SCID.^[41] Nine of the ten were cured of X-SCID.^[41] However, about three years after treatment, two of the children developed T-cell leukemia due to insertion of the IL2RG gene near the LMO2 gene and thereby activating the LMO2 gene (a known oncogene).^[42] A third child developed leukemia within two years of that study being published, likely as a direct result of the therapy.^[43] This condition is known as insertional mutagenesis, where the random insertion of a gene interferes with the tumor suppressor gene or stimulates an oncogene.^[34]There is currently no approved gene therapy on the market

If i recall correctly in that study though, they used Gamma-retroviruses, which were later shown to have a higher than normal propensity for integrating in spots that cause cancer (lentiviruses have been shown not to have this propensity, and using TALENs or ZFNs, or maybe CRISPR too, should allow one to choose the site of insertion).

I currently work in pharmacovigilance... and I think the regulators are way too cautious and conservative, its holding progress back. Even that study where 3 of the children died, 9 out of 10 were cured for a severe genetic disease (although not lethal).

To me that would be worth it, especially if it was changed from a gammaretrovirus to a lentivirus, and then from there we could move to targetted integration sites (review: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866806/ , another article... so many to choose from http://www.bloodjournal.org/content/117/20/5332?sso-checked=true ...not statements such as " γRV-mediated insertional mutagenesis" refer to GammaRetroVirus-mediated mutatgenesis)

The adenoviruses I made were very specific against cancer cells (tissue culture in the lab, controls were cultured embryonic stem cells, and differentiated human fibroblasts taken from the nearby university hospital, who got them from... *ahem* human foreskins after circumcision *ahem*). Of course... adenoviruses are quite weak, and the immune system would respond and neutralize subsequent treatments (the immune system could be temporarily suppressed), and there's always a risk of a more severe than usual allergic reaction... but there is so much potential being held back because a negative reaction that occurs in 1 out of a thousand people will lead to hundreds of thousands of people having negative reactions...

So I suspect any hTERT therapy will be likewise held back given the seemingly weak nature of the effect (since there are conflicting studies), the very long clinical trials needed to see a benefit (you'd have a hard time proving your drug has a therapeutic effect, and getting approval before the patent expires), and the significant expected risk of higher cancer incidence.

On so many issues, we have a social apparatus that isn't well suited to the real world.

 

 

[DNKKING]

Si les télomères s'allonge dans l'espace, cela veut dire que la vie est longue là bas ou pas ?

[Edit] English Translation: If telomere lengthens in space, does that mean that life is long there or not?

Edited April 25, 2019 by James Kerman
added translation

[James Kerman]

Welcome to the forum @DNKKING.

Unfortunately the forum is English only outside the international section. Using a translation service is fine if you wish to post in the general forum, however.

French translation of my post:
Bienvenue sur le forum @DNKKING. Malheureusement, le forum est uniquement en anglais en dehors de la section internationale. L'utilisation d'un service de traduction est acceptable si vous souhaitez poster sur le forum général.

[DNKKING]

Ok, I understand