SSRI drugs decrease lifespan

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Kasper
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SSRI drugs decrease lifespan

Postby Kasper » Fri 20 Jan 2017 17:44

See this article:

http://www.nature.com/nature/journal/v4 ... 05991.html

The SSRI drugs decrease lifespan, while 5-HT2 antagonist increase lifespan (in animal model). I was wondering if serotonin is somehow related to autophagy.

Here is the relevant table:

Image
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Aytundra
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Fri 20 Jan 2017 23:50

Kasper wrote:The SSRI drugs decrease lifespan,
okay,
The SSRI drugs hinders lifespan.
Kasper wrote:while 5-HT2 antagonist increase lifespan (in animal model)
how do you know that it increases lifespan?
could it not be,
while 5-HT2 antagonist drugs does not hinder lifespan as much (in C.elegans animal model) compared to SSRI drugs.
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Sat 21 Jan 2017 00:32

Point 1 - Control C.elegans can live for 40 days, (Evidence - See figure 3b. 3rd chart "Days vs. Fraction alive" ), that is Controls can live 10 days more than the drugged Mianserin C.elegans average,or 20 days more than the SSRI Fluoxetine (Prozac) drugged C.elegans. This shows that drugged C.elegans lifespan are hindered by drugs. Especially the lifespan of C.elegans are hindered more so by SSRIs such as Fluoxetine, Sertraline, and Paroxetine than the 5-HT antagonist, but still hindered by Mianserin.

Point 2 - If we are to say that Mianserin the 5-HT antagonist increases lifespan, than why are larvae C.elegans (Kids, teens, pre-adult of C.elegans) are dying when given Mianserin? (Evidence - See figure 3b. 1st chart "Larvae arrest (%) vs. Mianserin (µM)")
It is a drug, and it is dangerous to the pre-adult children of C.elegans.

Point 3 -The Supplementary Table 1, did not report the 200 µM of Mianserin, while their Figure 3b. 2nd chart "Mean lifespan (days) vs. Mianserin in 10, 50, 150 and 200 µM shows plots of points for adult C.elegans having a shorter lifespan as the dose of Mianserin increased. More drugs is not better.
And not reporting the 150 µM and 200 µM in the Supplementary Table is omitting data to the reader. Isn't it interesting that they did not report 200 µM in any of the 5-HT antagonist part of the Table? I think they are trying to persuade the readers to believe that Mianserin is exxxxxxxxxxxxtending lifespan, when really it is a drug that hinders lifespan, but less so than SSRIs.

Source of Figure 3b is from: Petrascheck M., Ye X., and Buck L.B. (2007) An antidepressant that extends lifespan in adult Caenorhabditis elegans. Vol 450, pg. 555. Nov 22, 2007. doi:10.1038/nature05991.
Mianserin C elegans Figure 3 of Petrascheck M. et al. 2007.JPG
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Sun 22 Jan 2017 04:59

I define an increase in lifespan as extending the age that the oldest human is known to die at.

For example,
Currently the oldest human reported alive is 116 years old (at least from the newspapers I am reading, or of my knowledge).
To show that a drug can increase lifespan would be to demonstrate that a drug taker can live to 145 years old.
That would demonstrate that the drug has an affect on increasing lifespan.

The drugs applied to the C.elegans did not extend C.elegans lifespan.
There is another Figure (fig 3 c first chart) inside that article that shows some Control C.elegans reaching 50 days old, not only 40 or 30 days old.
That means the oldest C.elegans is 50 days old (like humans at 116 years old), but there isn't a drug listed that brings the C.elegans to let's say 62.5 days old (or like to human equivalent age of 145 years old).

Hence this article did not demonstrate an increase in lifespan by taking drugs.

What this article could write is that: 5-HT antagonist seems to "assist" C.elegans destined* to die at day 10, 20, 25, 30, to live more days, that is ~ 10 days more, bringing these destined to die young to live a little longer like 20, 30, 35, 40 respectively.

* Destined, is a bit of a dicey word to use. We should read their data with some healthy dose of reader's skepticism, because sometimes we are not sure if labs cherry picked their data. It seems that the curve in different figures are variable. That there could be variation in the fraction of C.elegans living to age 10, 20, 30 inbetween the poles of 0 to 50 days. Some of these variations in curve patterns are due to differences in genetic groups of C.elegans used. If the DR eat-2 and clk-1 (Figure 3c.) shows a difference in curve structure patterns, it could be very well that the fraction of C.elegans are never exactly the same proportion in survival 'fraction alive' percentage. But if their data points were not cherry picked for 5-HT antagonist curves that are surpassing the controls. Then in the range of 48,49, 50 , 51, 52 µM would be the dose to test how those drugs assist C.elegans population destined to die between 10 - 25 days live 10 days more.


On another thought,
It could be more of a population ecology problem.
Maybe the wells are too crowded, the animals stressed, or there is not enough resources and hence in all charts, there is that curve that the population declines over time.
It reminds me of those ecology lectures where they talk about the number of offspring a species produces and the life cycle length of the species.
Flies produce lots of babies, but they only live a few days.
Birds produce 1 to 2 babies, but their species live for years.
Could it be a population effect thing on the species life cycle?
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Re: SSRI drugs decrease lifespan

Postby RRM » Sun 22 Jan 2017 19:03

5-HT3 receptors are involved in hippocampal autophagy Wu ZM et al
5-HT6 receptors are involved in the metabolism of proteins key in autophagy Ivachtchenko AV et al
N-acetylserotonin (precursor of melatonin) influences autophagy Hua Zhou et al Full free article

This one (full free article!) is interesting:
Antidepressants may spontaneously accumulate in membranes in the absence of their specific targets, evoking autophagy Chen J et al
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Sun 30 Apr 2017 03:53

i am a little bit confused, in regards to the whole serotonin systems and serotonin-drug systems.
RRM wrote:
Sun 22 Jan 2017 19:03
...involved in hippocampal autophagy ... involved in the metabolism of proteins key in autophagy ... influences autophagy...evoking autophagy
an autophagy is related to IF!...
and IF is the new warrior!...
and warrior mode is great!...
hence antidepressant is...-->... great!
-----
am I following your train of thoughts correctly?
Are you on the side that antidepressants are great?
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Sun 30 Apr 2017 04:03

Kasper wrote:
Fri 20 Jan 2017 17:44
The SSRI drugs decrease lifespan
Okay, I did a little bit of web searching and found a pretty map to scribble, with Microsoft Paint, with some of the numbers from the table of ages_life-span that the C.elegans in the study you posted http://www.nature.com/nature/journal/v4 ... 05991.html .
It looks like that SSRI is terrible for C.elegans's life-span.
It also looks like the shape of the drug matters on how life-span-detrimental it can be.

Something is fishy with their chart:
But without the higher concentrations 250µM , 200µM , 100µM of drugs applied on the C.elegans, for the Tetracyclic antidepressants like Mianserin (measured only at the low dose of 50µM), and First Generation Tricyclic antidepressants (TCA) Iminodibenzyl derivative like Imipramine, we cannot compare them to the Third generation Selective serotonin reuptake inhibitors (SSRI) like Sertraline which were measured at 50µM and 250µM. And with higher doses C.elegans suffered a shorter lifespan.

By the way some of these molecules look like the shape of beta-carboline! yikes!
SSRI and 5HT antagonist pic.png
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Re: SSRI drugs decrease lifespan

Postby RRM » Sun 30 Apr 2017 19:26

Aytundra wrote:
Sun 30 Apr 2017 03:53
Are you on the side that antidepressants are great?
Ha ha, no of course not!
Autophagy can be influenced by, and influences many mechanisms.
So, you may influence autophagy locally in various ways, including with many types of drugs, including SSRIs.
However, this chemically induced/inhibited autophagy can never reach as many cells as fasting can, plus there is this 'issue' of the side effects, of course.
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Re: SSRI drugs decrease lifespan

Postby Kasper » Mon 01 May 2017 22:12

The idea proposed in this study, IIRC is that anti serotonin drugs increase hunger and that the increase of hunger kind of mimics fasting somehow (body feels like there is not enough energy).

I wouldnt go for anti serotonin drugs except maybe if you have severe digestive problems and a wai inspired diet enough doesnt help. I think some of those drugs can help the body not to overreact to certain food, and help it just peacefully digest it. (dont take this as advice)

Also sometimes a severely stressed body (and cortisol also increases serotonin) can have a complete lack of appetite. Kind of as the body is in hibernation (zombie mode).

Talking here for a great deal out of personal experience, from my experiments, with pro serotonin and anti serotonin drugs/supplements/food.
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Mon 01 May 2017 23:57

Kasper wrote:
Mon 01 May 2017 22:12
pro serotonin and anti serotonin drugs
Kasper could you answer some questions about your terminologies?

In Kasper's understanding:
Does "anti serotonin drugs" decrease/increase the quantity of serotonin molecules?___________
Does "pro serotonin drugs" decrease/increase the quantity of serotonin molecules?___________
Name 1 "anti serotonin drug":_____________
Name 1 "pro serotonin drug":_____________
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Tue 02 May 2017 22:21

Here maybe diagrams that i sketched will help explain my thinking {don't know if what i recall from classes are correct.}.
Brain cells communicate over a distance..JPG
Neurotransmitters allow cells to communicate..JPG
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Tue 02 May 2017 22:22

Imo, Serotonin receptor sketch.JPG
Imo, Serotonin reuptake inhibitor drug on reuptake protein sketch.JPG
Imo, Serotonin receptors drug on Serotonin receptors sketch.JPG
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Re: SSRI drugs decrease lifespan

Postby Aytundra » Sat 06 May 2017 23:24

Imo blocked reuptake proteins means no more neurotransmitters for cell communication..JPG
Imo too many drug molecules stops neurons communication..JPG
C.elegans serotonin drugs.JPG
Have you ever wondered why that the list of treatments used on C.elegans only contained Serotonin at 3000µM? while all the other Neurotransmitter drugs are 250µM or less?
That is because everything else of the list of drugs is a poison.
A poison is something of a number of molecules that the cells cannot regulate at a point and the cell communication breaks.

But what about serotonin? Why could it have 3000µM and live for an average of 22 days?
Serotonin is a molecule that C.elegans cells naturally make.
Hence those cells can regulate the molecule.
Anything else not naturally made by c.elegans' cells are a drug, something foreign and not natural to the cells of C.elegans, of which has no system to regulate the drug.
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Re: SSRI drugs decrease lifespan

Postby RRM » Wed 10 May 2017 17:29

I find it interesting that 1000 µM serotonin results in a 8% decrease in lifespan,
whereas 3000 µM results in a 6% decrease in lifespan.
If that correlation was linear, a 9000 µM serotonin supplement would result in no decrease/increase, and additional serotonin in an increase in lifespan...

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