bio~tolerance - lifespan

bio~tolerance

challenges / lifespan

https://youtu.be/ynTrFZbrAl8

Nightcore - Catch Fire

Hi all! I am mainly interested in research geared at increasing lifespan via biohacking. Are there any members here with similar mindsets?

RentableZulu

Hi all! I am mainly interested in research geared at increasing lifespan via biohacking. Are there any members here with similar mindsets?

here

1

14:59

what r ur interventions so far

15:00

I do FMD, endurance training, Rapamycin, plant based diet

1

Nice! I take NMN & Resveratrol, endurance training and fast. I would like to next incorporate some calorie restriction or do a plant based diet

15:06

It’s nice to meet someone of similar mindset though. Can you tell me about FMD?

emoji_37

1

RentableZulu

It’s nice to meet someone of similar mindset though. Can you tell me about FMD?

yeah

15:08

fasting mimicking diet by Valter Longo

15:09

1200 kcal first day, then 725 kcal for the next 4 days, slowly refeed in 500 kcal increments

15:09

he lowers protein to 20 g but I didn't manage that with full nutrient intake I don't like to supplement a lot of minerals

15:09

so my protein intake is 30 g

15:10

but it's low enough considering the amount of endurance training I do while doing this

15:10

I take 5mg Rapamycin on day 3 when AMPK is at it's highest

15:11

this might be too much autophagy tho, I get muscle pains and headache

15:11

my goal is to nook cancerous cells so I think it's worth it

15:12

after this I revert to high calorie plant based diet with around 100 g protein. lots of endurance training, calisthenics up to 2 times a day

15:12

maxing out push ups and pull ups

The self discipline it must take to do that! That is pretty intense

GG @RentableZulu, you just advanced to level 1!

There a substance that emulate exercise

RentableZulu

The self discipline it must take to do that! That is pretty intense

with my stack, not really, it makes it easy. Without it, yes it does take some effort

ibtisam.midlet

There a substance that emulate exercise

What do you mean?

Deleted User

with my stack, not really, it makes it easy. Without it, yes it does take some effort

Your stack?

ibtisam.midlet

There a substance that emulate exercise

My first thought would be a compound found in lemon myrtle ( Causarinin) which are shown to activate dormant skeletal muscle satellite cells in both Vitro and Vivo

judas

My first thought would be a compound found in lemon myrtle ( Causarinin) which are shown to activate dormant skeletal muscle satellite cells in both Vitro and Vivo

nice

RentableZulu

What do you mean?

There a substance that trigger the same pathways that exercise trigger in muscle , causing you to gain muscle without need for exercise It does trigger fat burn and protein synthesis, but not the runner' high reward

ibtisam.midlet

There a substance that trigger the same pathways that exercise trigger in muscle , causing you to gain muscle without need for exercise It does trigger fat burn and protein synthesis, but not the runner' high reward

what sub

RentableZulu

Hi all! I am mainly interested in research geared at increasing lifespan via biohacking. Are there any members here with similar mindsets?

i am giving my 17 year old cat medicine against muskledystrophy and breaking down of her organism. Tradeoff increased cancer risk. If she gets cancer the medicine will increase the growth rathe drastical

RentableZulu

Nice! I take NMN & Resveratrol, endurance training and fast. I would like to next incorporate some calorie restriction or do a plant based diet

i take vit B3 instead of NMN helps also

Mabus Tiefsee

i am giving my 17 year old cat medicine against muskledystrophy and breaking down of her organism. Tradeoff increased cancer risk. If she gets cancer the medicine will increase the growth rathe drastical

Damn 17 yrs

06:53

How old do cats live up to?

let's say it that way, her kittens already died because of old age

06:54

Image attachment

06:55

The average lifespan for a pet cat is probably around 13 to 14 years. However, although their lifespan varies, a well cared for cat may commonly live to 15 or beyond, some make it to 18 or 20 and a few extraordinary felines even pass 25 or 30 years of age.

Mabus Tiefsee

The average lifespan for a pet cat is probably around 13 to 14 years. However, although their lifespan varies, a well cared for cat may commonly live to 15 or beyond, some make it to 18 or 20 and a few extraordinary felines even pass 25 or 30 years of age.

Will u buy another cat after that one dies?

already got one. a nearly feral one. He needs to take care of the mice.

1

Mabus Tiefsee

already got one. a nearly feral one. He needs to take care of the mice.

How old is that one

uhm.... dunno around 3-5?

The Blur

Will u buy another cat after that one dies?

i hope to prevent her death as long as possible. A year ago i needed to give her the hormonal boost every feew months. But recently it became every other week. . .

GG @Mabus Tiefsee, you just advanced to level 5!

Mabus Tiefsee

i am giving my 17 year old cat medicine against muskledystrophy and breaking down of her organism. Tradeoff increased cancer risk. If she gets cancer the medicine will increase the growth rathe drastical

what's the medicine

raw calf liver, the cat loves it. never heated above 40°C or frozen. High in IGF1 (and most likely a bunsh of other liver derivated hormones)

Mabus Tiefsee

raw calf liver, the cat loves it. never heated above 40°C or frozen. High in IGF1 (and most likely a bunsh of other liver derivated hormones)

Peptides are not orally active

veganpermanently

Peptides are not orally active

i tested it, it works oraly. Take a look into "that works - calf liver" there are the experiments i made listed

Mabus Tiefsee

i tested it, it works oraly. Take a look into "that works - calf liver" there are the experiments i made listed

It does something else unrelated to IGF1. Divine protein shakes don't exist dudes just gay

veganpermanently

It does something else unrelated to IGF1. Divine protein shakes don't exist dudes just gay

yeah if you say so.... however it causes the exact symptoms of agromegaly. Including growth of the hands. Do proteibshakes let your hands grow?

ibtisam.midlet started a thread. 08-Aug-22 03:23 PM

ibtisam.midlet

There a substance that trigger the same pathways that exercise trigger in muscle , causing you to gain muscle without need for exercise It does trigger fat burn and protein synthesis, but not the runner' high reward

Hey what substance is this?

RentableZulu

Hey what substance is this?

its name: monovalent follistatin 3like effect on muscle: induced muscle fiber hypertrophy and increased muscle mass https://pubmed.ncbi.nlm.nih.gov/34113826/ on bone: Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening https://pubmed.ncbi.nlm.nih.gov/25937185/

Systemic administration of monovalent follistatin-like 3-Fc-fusion ...

Targeting the signaling pathway of growth differentiation factor 8 (GDF8), also known as myostatin, has been regarded as a promising strategy to increase muscle mass in the elderly and in patients. Accumulating evidence in animal models and clinical trials has indicated that a rational approach is t …

Follistatin-like 3 is a mediator of exercise-driven bone formation ...

Exercise is vital for maintaining bone strength and architecture. Follistatin-like 3 (FSTL3), a member of follistatin family, is a mechanosensitive protein upregulated in response to exercise and is involved in regulating musculoskeletal health. Here, we investigated the potential role of FSTL3 in e …

1

01:53

@RentableZulu Inject it in pig and we have a lot of meat

1

https://www.pnas.org/doi/10.1073/pnas.0604893104

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.

12:27

Lack of myostatin results in excessive muscle growth but impaired force generation

emoji_52

5

12:28

We report that, despite a larger muscle mass relative to age-matched wild types, there was no increase in maximum tetanic force generation, but that when expressed as a function of muscle size (specific force), muscles of myostatin-deficient mice were weaker than wild-type muscles

12:29

https://pubmed.ncbi.nlm.nih.gov/34544873/

Follistatin mediates learning and synaptic plasticity via regulatio...

The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing informati …

better underpromise and overdeliver than be caught lacking

There is substantially more data that has to be presented about the efficacy of follistatin for it to be considered viable for muscle growth

from what I've heard from some human guinea pigs follistatin was ineffective

Ive heard that its prohibitively expensive in comparison to anabolic steroids

12:33

Even then the viability of follistatin in context of heart growth may put someone at increased risk of cardiomyopathy

12:34

https://pubmed.ncbi.nlm.nih.gov/27430031/

Follistatin like 1 Regulates Hypertrophy in Heart Failure with Pres...

These findings indicate that Fstl1exerts therapeutic effects by modulating cardiac hypertrophy in HFpEF.

intranasal test is attractive to me for a long time

Intranasal test definitely shows promise for increasing dopamine and serotonin levels but theres substantial evidence to show that superphysiological levels of testosterone are detrimental to cognitive health

also tomatidine sounds good in terms of muscle growth

12:37

tho' the gains are probably marginal

Ive heard rhat only anataeus labs carries tomatadine

12:38

Hypothalamic erythropoeitin expression modulates muscle and apipocyte function through a variety of mechanisms.

Pax1l

Ive heard rhat only anataeus labs carries tomatadine

certain tomato cultivars have sufficient amounts in leaves

Tomato is a nightshade

there is great variance among the different cultivars tho

Pax1l

Tomato is a nightshade

based plant

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938905/

Regulation of muscle and metabolic physiology by hypothalamic eryth...

The glycoprotein hormone erythropoietin (EPO) is required for erythropoiesis, and the kidney is the primary site of adult EPO synthesis. Limited evidence has suggested that EPO could be detectable in the brain under certain conditions, but it remains ...

12:42

Intranasal erythropoeitin and erythropoeitin agonists like ara290 may promote metabolic functions to mitigate hypithalamic inflammation

12:43

https://www.nature.com/articles/ncomms1526

Disrupted erythropoietin signalling promotes obesity and alters hyp...

Nature Communications - Erythropoietin circulates in the blood and is essential for erythropoiesis but its role in metabolic homeostasis has not been examined. Tenget al. show that when the...

ibtisam.midlet

There a substance that trigger the same pathways that exercise trigger in muscle , causing you to gain muscle without need for exercise It does trigger fat burn and protein synthesis, but not the runner' high reward

its a peptide right i think there are multiple that do that

https://youtu.be/KXG0jpC1LjM

NutritionFacts.org

The Best Diet for Healthy Aging

NAC & Glutathione Are Transforming Aging! New Study

@sono, you have advanced to lvl 2 respect++ emoji_51

emoji_51

sono

NAC & Glutathione Are Transforming Aging! New Study

Not very new, oxidative stress causes inflammation and consequently aging (edited)

Image attachment

04:29

https://commons.m.wikimedia.org/wiki/File:Leading_cause_of_death_world.png#

File:Leading cause of death world.png

04:35

Cardiovascular considered a natural death

ibtisam.midlet pinned a message to this channel. 12-Sep-22 05:01 AM

**lifespan studies**
subs           lifespan   dose
Repamycin      +60%       8mg/kg
aspirin        +52%
calorie-restri +35%       na
methio restri  +33%       -40% RDA
minocycline    +27%
=human median lifespan(72y)x307%=223y
--------- time wasting ----------
Captopril      +23%
Acarbose       +22%
NAC            +17%
NDGA           +17%
resveratrol    +15.8%
Canagliflozin  +14%
17-α-estradiol +12%
curcumin       +11%
melatonin      +10%       2-20mg/l water
quercetin      +9.5%
Protandim      +7%
Metformin      +5.8%      0.1%/diet
gluconic acid  +5.5% 
glycine         +5%       8%/diet 

links:
Melatonin>>https://pubmed.ncbi.nlm.nih.gov/12670632/
Calories>>https://www.medicalnewstoday.com/articles/avoiding-late-night-meals-may-have-anti-aging-benefits
Metaformin>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736576/#
Repamycin>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996648/
others>>https://pubmed.ncbi.nlm.nih.gov/34687363/
methionine restriction>>https://journals.physiology.org/doi/full/10.1152/ajpregu.00837.2009 glycine(mitigate methionine toxicity)>>https://pubmed.ncbi.nlm.nih.gov/30916479/ Acarbose, 17-α-estradiol>>https://pubmed.ncbi.nlm.nih.gov/24245565/ 
Protandim>>https://kommunikasjon.ntb.no/pressemelding/nia-study-confirms-protandim-nrf2-synergizer-extends-life?publisherId=4954260&releaseId=11780456  
Canagliflozin>> https://pubmed.ncbi.nlm.nih.gov/32990681/ 
Captopril>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769152/#:~:text=At%20the%20optimal%20concentration%20of,population%20that%20are%20longest%20lived.

interesting subs:
TM5441 
Ciclopirox 
astaxanthin
5-Aminoimidazole-4-carboxamide ribonucleotide(AICAR)
acadesine
Bacitracin

(edited)

ibtisam.midlet pinned a message to this channel. 12-Sep-22 05:10 AM

ibtisam.midlet

**lifespan studies**
subs           lifespan   dose
Repamycin      +60%       8mg/kg
aspirin        +52%
calorie-restri +35%       na
methio restri  +33%       -40% RDA
minocycline    +27%
=human median lifespan(72y)x307%=223y
--------- time wasting ----------
Captopril      +23%
Acarbose       +22%
NAC            +17%
NDGA           +17%
resveratrol    +15.8%
Canagliflozin  +14%
17-α-estradiol +12%
curcumin       +11%
melatonin      +10%       2-20mg/l water
quercetin      +9.5%
Protandim      +7%
Metformin      +5.8%      0.1%/diet
gluconic acid  +5.5% 
glycine         +5%       8%/diet 

links:
Melatonin>>https://pubmed.ncbi.nlm.nih.gov/12670632/
Calories>>https://www.medicalnewstoday.com/articles/avoiding-late-night-meals-may-have-anti-aging-benefits
Metaformin>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736576/#
Repamycin>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996648/
others>>https://pubmed.ncbi.nlm.nih.gov/34687363/
methionine restriction>>https://journals.physiology.org/doi/full/10.1152/ajpregu.00837.2009 glycine(mitigate methionine toxicity)>>https://pubmed.ncbi.nlm.nih.gov/30916479/ Acarbose, 17-α-estradiol>>https://pubmed.ncbi.nlm.nih.gov/24245565/ 
Protandim>>https://kommunikasjon.ntb.no/pressemelding/nia-study-confirms-protandim-nrf2-synergizer-extends-life?publisherId=4954260&releaseId=11780456  
Canagliflozin>> https://pubmed.ncbi.nlm.nih.gov/32990681/ 
Captopril>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769152/#:~:text=At%20the%20optimal%20concentration%20of,population%20that%20are%20longest%20lived.

interesting subs:
TM5441 
Ciclopirox 
astaxanthin
5-Aminoimidazole-4-carboxamide ribonucleotide(AICAR)
acadesine
Bacitracin

(edited)

@veganpermanently hey, what other subs that cause this

ibtisam.midlet

@veganpermanently hey, what other subs that cause this

Berberine, fucoxanthin, light and high temperature exposure avoidance

ibtisam.midlet

@veganpermanently hey, what other subs that cause this

https://pubmed.ncbi.nlm.nih.gov/34687363/

A collective analysis of lifespan-extending compounds in diverse mo...

Research on aging and lifespan-extending compounds has been carried out using diverse model organisms, including yeast, worms, flies and mice. Many studies reported the identification of novel lifespan-extending compounds in different species, some of which may have the potential to translate to the …

06:24

Aspirin, minocycline, NAC, and 'nordihydroguairetic acid'

Yana

https://pubmed.ncbi.nlm.nih.gov/34687363/

Thank you thank you 981262939434659892

981262939434659892

ibtisam.midlet

@veganpermanently hey, what other subs that cause this

https://www.biorxiv.org/content/10.1101/698001v1.full

Astaxanthin extends lifespan via altered biogenesis of the mitochon...

Astaxanthin is a keto -carotenoid produced in some bacteria and algae, which has very important industrial applications (i.e., in cosmetics, coloring additive in aquaculture and as a dietary supplement for human). Here, we analyzed the molecular basis of Astaxanthin-mediated prolongevity in the model organism, Caenorhabditis elegans . The increa...

11:54

https://pubmed.ncbi.nlm.nih.gov/26292053/

Fucoxanthin increases lifespan of Drosophila melanogaster and Caeno...

The pharmacological activation of stress-defense mechanisms is one of the perspective ways to increase human lifespan. The goal of the present study was to study the effects on lifespan of Drosophila melanogaster and Caenorhabditis elegans of two carotenoids: ß-carotene and fucoxanthin, which are bi …

11:56

all carotenoids are great but I think astaxanthin and fucoxanthin are the best candidates because fucoxanthin can help nook cancer cells and astaxanthin is brain penetrant and can help with neurodegeneration

11:57

Lutein and zeaxanthin are great for eyesight

https://pubmed.ncbi.nlm.nih.gov/22114686/

FDA-approved drugs that protect mammalian neurons from glucose toxi...

Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, …

12:10

Ciclopirox is dramatic. 41% average lifespan increase in C. elegans. Promising for neurodegeneration. Might also be acutely nootropic when taken oral, no one has tried it yet.

1

veganpermanently

all carotenoids are great but I think astaxanthin and fucoxanthin are the best candidates because fucoxanthin can help nook cancer cells and astaxanthin is brain penetrant and can help with neurodegeneration

If only it didn't fuck w 5α-reductase

Yana

If only it didn't fuck w 5α-reductase

astaxanthin?

12:38

I'd consider that a good thing esp with my hormone mimetic research chemicals

️

@Yana https://www.reddit.com/r/acne/comments/4qsttz/minocycline_gave_me_severe/ do you know how it cause depresonalization, its iNOS inhibitor and increase interleukin (IL)-10, IL-15 and vascular endothelial growth factor (VEGF) https://iv.iiarjournals.org/content/28/1/21 its potent psychoactive, interest me for the underlying mechanism

r/acne - Minocycline gave me severe depersonalization/negative psyc...

5 votes and 5 comments so far on Reddit

Minocycline Modulates Cytokine and Gene Expression Profiles in the ...

An effective countermeasure against radiation damage to normal tissues is urgently needed. The major goal of the present study was to determine if minocycline could modify the immunomodulatory effects of radiation on the brain. C57BL/6 mice were treated with minocycline intraperitoneally for 5 days beginning immediately before total-body exposur...

03:46

its a drug!!

ibtisam.midlet

@Yana https://www.reddit.com/r/acne/comments/4qsttz/minocycline_gave_me_severe/ do you know how it cause depresonalization, its iNOS inhibitor and increase interleukin (IL)-10, IL-15 and vascular endothelial growth factor (VEGF) https://iv.iiarjournals.org/content/28/1/21 its potent psychoactive, interest me for the underlying mechanism

I assume antibiotics are quite the rabbithole so idrk. Had no idea it would be psychoactive. Maybe in the study where it enhanced lifespan they kept the animals' guts sterile or something like that that's hard to replicate in people. Just a guess tho

ibtisam.midlet

**lifespan studies**
subs           lifespan   dose
Repamycin      +60%       8mg/kg
aspirin        +52%
calorie-restri +35%       na
methio restri  +33%       -40% RDA
minocycline    +27%
=human median lifespan(72y)x307%=223y
--------- time wasting ----------
Captopril      +23%
Acarbose       +22%
NAC            +17%
NDGA           +17%
resveratrol    +15.8%
Canagliflozin  +14%
17-α-estradiol +12%
curcumin       +11%
melatonin      +10%       2-20mg/l water
quercetin      +9.5%
Protandim      +7%
Metformin      +5.8%      0.1%/diet
gluconic acid  +5.5% 
glycine         +5%       8%/diet 

links:
Melatonin>>https://pubmed.ncbi.nlm.nih.gov/12670632/
Calories>>https://www.medicalnewstoday.com/articles/avoiding-late-night-meals-may-have-anti-aging-benefits
Metaformin>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736576/#
Repamycin>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996648/
others>>https://pubmed.ncbi.nlm.nih.gov/34687363/
methionine restriction>>https://journals.physiology.org/doi/full/10.1152/ajpregu.00837.2009 glycine(mitigate methionine toxicity)>>https://pubmed.ncbi.nlm.nih.gov/30916479/ Acarbose, 17-α-estradiol>>https://pubmed.ncbi.nlm.nih.gov/24245565/ 
Protandim>>https://kommunikasjon.ntb.no/pressemelding/nia-study-confirms-protandim-nrf2-synergizer-extends-life?publisherId=4954260&releaseId=11780456  
Canagliflozin>> https://pubmed.ncbi.nlm.nih.gov/32990681/ 
Captopril>>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769152/#:~:text=At%20the%20optimal%20concentration%20of,population%20that%20are%20longest%20lived.

interesting subs:
TM5441 
Ciclopirox 
astaxanthin
5-Aminoimidazole-4-carboxamide ribonucleotide(AICAR)
acadesine
Bacitracin

(edited)

ok lifespan solved, what's next 983795135575883818

983795135575883818

@everyone

What does time wasting mean? The 2nd part?

Evelien

What does time wasting mean? The 2nd part?

Very weak to consider taking them

1

ibtisam.midlet

ok lifespan solved, what's next 983795135575883818

983795135575883818

@everyone

thoughts on 5-Aminoimidazole-4-carboxamide ribonucleotide(AICAR) and acadesine injections too, would be stronger ampk activator compared to metformin or Berberine (edited)

09:30

And complement rapamycin

ibtisam.midlet

@Yana https://www.reddit.com/r/acne/comments/4qsttz/minocycline_gave_me_severe/ do you know how it cause depresonalization, its iNOS inhibitor and increase interleukin (IL)-10, IL-15 and vascular endothelial growth factor (VEGF) https://iv.iiarjournals.org/content/28/1/21 its potent psychoactive, interest me for the underlying mechanism

Nurr1 agonist

09:32

I tried another tetracyclin called doxycyclin it was hell

emoji_13

1

09:33

on paper it looks very nice in the real world makes you depressed and some people even suicidal

09:33

I felt dulled, unmotivated, dazed and dissociated

09:34

lasted the whole treatment of 2 weeks + a few days after which is exactly the elimination time (edited)

machineyadav

thoughts on 5-Aminoimidazole-4-carboxamide ribonucleotide(AICAR) and acadesine injections too, would be stronger ampk activator compared to metformin or Berberine (edited)

too expensive

veganpermanently

all carotenoids are great but I think astaxanthin and fucoxanthin are the best candidates because fucoxanthin can help nook cancer cells and astaxanthin is brain penetrant and can help with neurodegeneration

if you take them out of your food. Prefer plants who had a bad life, they produce more stress responses like those protecting enzymes

Mabus Tiefsee

if you take them out of your food. Prefer plants who had a bad life, they produce more stress responses like those protecting enzymes

astaxanthin and fucoxanthin are not expressed in plants

my bad, had the red and blue pigments of most berrys in mind but forgot the name

Mabus Tiefsee

my bad, had the red and blue pigments of most berrys in mind but forgot the name

they're algal carotenoids. so-called food of the future we can't even formulate to make a nutrient complete diet. but they're good supplements

veganpermanently

astaxanthin?

Yes, it does modulate 5AR, but it's very weak. Subjectively less so than things like curcumin. I'm sensitive to 5AR inhibitors, and I take 12mg of astaxanthin most days

Odder_Sea (Glowie)

Yes, it does modulate 5AR, but it's very weak. Subjectively less so than things like curcumin. I'm sensitive to 5AR inhibitors, and I take 12mg of astaxanthin most days

I have never had a bad response to 5AR inhibitors. Quite the contrary but probably due to the other effects. 5HT1A agonists however kill my erection quality and put me in a degenerated mood

11:19

I would guess this is bcs I have very low test production anyways, the inhibition does nothing because there's no substrate for the enzyme to work on

veganpermanently

I have never had a bad response to 5AR inhibitors. Quite the contrary but probably due to the other effects. 5HT1A agonists however kill my erection quality and put me in a degenerated mood

I think I suffer more from a deficiency of DHT than total test (though that's always been in the low side for me) So I have to be careful with things that inhibit DHT. Longvida curcumin and astaxanthin are slight 5AR inhibitors, but there benefits are worth any potential downsides IMO

Odder_Sea (Glowie)

I think I suffer more from a deficiency of DHT than total test (though that's always been in the low side for me) So I have to be careful with things that inhibit DHT. Longvida curcumin and astaxanthin are slight 5AR inhibitors, but there benefits are worth any potential downsides IMO

Why do you think high DHT is a good thing?

11:33

AR signalling can be replaced with ACP105, I think that's healthier than having high DHT because the efficacy can't reach 100% which would grow the prostate. Many people think the GABAergic DHT metabolites are what influences behavior but that can be easily contested and I think a beta estrogen agonist is sufficient for this. so ACP105 and AC186 are probably golden but we can't source AC186 rn

11:34

It's resemblance to BPA and possible GPER activity is kinda worrying tho'

veganpermanently

Why do you think high DHT is a good thing?

I don't. I just don't think that low DHT is a great thing, either, due to impairments of neurosteroid signalling and lethargy, fatigue, etc. I'm hoping that microdose prozac may offset the Neurosteroid issues

11:36

Probably goldilocks zone, as usual. I just think that I'm a bit below the ideal threshold

Odder_Sea (Glowie)

I don't. I just don't think that low DHT is a great thing, either, due to impairments of neurosteroid signalling and lethargy, fatigue, etc. I'm hoping that microdose prozac may offset the Neurosteroid issues

I don't think allopregnenalone deficiency is the issue

11:36

from the studies I've seen DHT doesn't rescue behavioral or cognitive impairments or upregulate brain AR on it's own

11:37

it's dependent on it's metabolite 3 beta androstanediol

11:39

ACP105+AC186 combination mimics this, upregulates AR, reduces amyloid beta in rodent models, rescues behavior

11:41

Estriol is interesting. It's an estrogen that acts as an antiestrogen in presence of estradiol. It has a higher affinity for the beta subtype and is an antagonist at GPER

ibtisam.midlet

ok lifespan solved, what's next 983795135575883818

983795135575883818

@everyone

Quality of life!

I've been trying to conjure a Complete Hormone Augmentation Therapy if anyone is interested in helping me join up in a thread https://discord.com/channels/1011367020182376478/1018196332747427882/1018656333374955530

Starting with making sure we aren't enslaved to a big brother authoritarian body with that extra lifespan

1

11:47

Imagine making people live eternally only to be enslaved

Free Will I Am

Starting with making sure we aren't enslaved to a big brother authoritarian body with that extra lifespan

https://discord.com/channels/1011367020182376478/1011367429936529550/1011368816829288478

11:48

u sound fit for my server

11:48

https://discord.gg/4SPTavNJ

Going to see college

11:48

So we have Korean looking

we need to learn biochem and build labs asap

11:49

and refine algae and mushroom cultivation

Free Will I Am

Quality of life!

N this how to have a happy life https://discord.com/channels/1001420842179239936/1001424018420805710/1018403918537039912

ibtisam.midlet

N this how to have a happy life https://discord.com/channels/1001420842179239936/1001424018420805710/1018403918537039912

I'm pretty sure I need Cannabis

11:53

probably every 2 weeks

11:53

the mindset becomes incredibly dark when I don't do that

it works everyday btw

11:54

Canb

yeah but I don't need it every day and it's bad for neurogenesis, PFC function and grey matter

You can feel it if you know your baseline exctly

rare use has a differential effect

veganpermanently

rare use has a differential effect

Selectivity +_+

I blast it once a month

11:55

that seems to have the best effect so far

11:55

haven't tried once in 2 weeks

11:56

the problem with this once a month thing is that I become very edgy at the tail end of it

You know your why occasional use give clean effect ha? (edited)

snappy, aggressive

ibtisam.midlet

You know your why occasional use give clean effect ha? (edited)

differential effect on BDNF secretion

11:57

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791800/

Preliminary evidence of cannabinoid effects on brain-derived neurot...

Acute and chronic exposure to cannabinoids has been associated with cognitive deficits, a higher risk for schizophrenia and other drug abuse. However, the precise mechanism underlying such effects is not known. Preclinical studies suggest that cannabinoids ...

11:57

the worst thing to do is to consume small amounts all the time

11:57

you can either escalate use or use sparingly

11:57

but use escalation doesn't influence BDNF at all

11:57

and rare use increases it

Generally because canab agonist good pathways in canabinoid system causing it to tolerance faster

veganpermanently

differential effect on BDNF secretion

Yeah things like cb receptor use bdnf etc

I do the McKenna method

What's it

ibtisam.midlet

What's it

As much as you can find of the best weed you can find. Once a month. In total darkness and silence. Lots of deep breathing

12:00

I put it in the oven for 15 mins at 115°C then eat it on a little bit of food

12:01

otherwise fasting

Its illegal there?

it's decriminalized

12:01

i.e. u get a fine if they find it on you

mmmh

12:02

Love you ❤

981262939434659892

1

@ibtisam.midlet, you have advanced to lvl 18 respect++ emoji_51

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ibtisam.midlet

Love you ❤

mmm where did that come from

12:03

kinda needed it (edited)

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1

12:03

emoji_37

veganpermanently

ACP105+AC186 combination mimics this, upregulates AR, reduces amyloid beta in rodent models, rescues behavior

That sounds promising

veganpermanently

the worst thing to do is to consume small amounts all the time

What about "small" amounts intermittently (oral Delta-8/9) a few times per month?

veganpermanently

too expensive

it costs only 60$ (edited)

18:52

Actually the dose was higher

18:53

Bpc-157 and AICAR is almost same price

18:55

Acadesine costs 50$

18:55

Cheaper when buying in bulk

18:59

Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%.

19:00

AICAR is potent exercise mimetic

Odder_Sea (Glowie)

What about "small" amounts intermittently (oral Delta-8/9) a few times per month?

I don't think that would make a substantial change in whatever direction... as long as your brain recovers

@veganpermanently, you have advanced to lvl 13 respect++ emoji_51

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machineyadav

it costs only 60$ (edited)

where

machineyadav

Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%.

can u source it pls

veganpermanently

where

Peptide science

02:53

https://www.peptidesciences.com/aicar-50mg

AICAR is an analogue of adenosine monophosphate. It has been used clinically to protect against cardiac ischemia following heart attack. AICAR has antioxidant properties and may therefore help to slow

02:53

10% cheaper in bulk

machineyadav

https://www.peptidesciences.com/aicar-50mg

thank u can u sauce the study showing enhanced endurance

02:54

the dose is 10 mg no?

veganpermanently

thank u can u sauce the study showing enhanced endurance

https://pubmed.ncbi.nlm.nih.gov/18674809/

AMPK and PPARdelta agonists are exercise mimetics - PubMed

The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metab …

02:54

There are two AICAR with same name

02:54

One is acadesine and another is also aicar

02:55

We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice.

dude wtf

02:57

look at the dose

Oh

machineyadav

Oh

U'd need to inject about a gram and a half to get the effects in the study

Acadesine dose may differ from other AICAR

this is why I said it's too expensive

Only buying in bulk would be cheap

If I had that kind of money I would buy a million things before I spend 1800 USD on a single dose of AICAR

42.5$ usd for 50mg acadesine

03:00

Even less when buying more

machineyadav

42.5$ usd for 50mg acadesine

again, check effective dose

03:00

they're adenosine mimetics

03:01

therefore, dose required is very probably in the gram range

Hmmm didn't looked at the dose

03:01

I am searching for good PPAR agonist too

machineyadav

Hmmm didn't looked at the dose

go further yung Sith

03:02

Have plans to buy acadesine when I have >500$

03:03

If 50mg costs less than 30$

machineyadav

Have plans to buy acadesine when I have >500$

that is consumerist mentality

03:04

consume knowledge before spending money if you're being consumerist

Since mice is around 50g weight (edited)

03:04

And they used 500mg/kg

machineyadav

Since mice is around 50g weight (edited)

* body weight / 12

How much human equivalent dose will be?

500 * 70 / 12 for me

03:05

3 g dose for a 70 kg human

Oh

smaller dose was 250

03:05

still 1500 mg

as I said these substances are not magic

03:06

they mimic adenosine thus activate AMPK

03:06

might as well increase endogenous adenosine

I will try still injecting some if i get hands on it and still search for better alternatives

03:07

The gene upregulation may last for some time

they only do this to exclude effects of the interventions required to increase endogenous adenosine

03:08

they're quite literally research chemicals, not much use case in the real world

03:08

low dose Berberine feels good to me

Metformin is what I prefer now

@machineyadav, you have advanced to lvl 7 respect++ emoji_51

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Yet to experiment with Berberine

thinking about making a field to grow the berries

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1

03:09

they're quite easy to grow and very resilient plants

Actually effective dose for me would be 384.61mg/kg? (edited)

03:15

Image attachment

03:15

I used this formula

03:16

Damn still very lot

03:16

03:16

I came across another compound called mk but it induced cardiac hypertrophy

forget about adenosine mimetics

Also O304 (edited)

just train my guy

03:19

perfect your diet, throw out the animal products

03:20

a bit of berberine, some taurine, etc.

03:20

I found a way to increase erythropoiesis substantially

03:21

it's an iron chelator but 10x stronger than DFO with less iron chelating capacity

1

veganpermanently

I found a way to increase erythropoiesis substantially

Epo or Ara?

machineyadav

Epo or Ara?

what's ara

03:23

it's the same MoA as DFO

03:23

HIF1 pathway

veganpermanently

what's ara

It's epo analogue iirc

veganpermanently

HIF1 pathway

Bromantane enhaces HIF-1a

03:26

DFO also enhaces neurotrophins and epo

03:26

Like GDNF

03:26

I looked at M60 which got me interested in DFO

03:26

Because both work same

yeah well I think this might be unrelated to iron chelation judging from the effects of the compound I'm looking at

Pax said M60 was too expensive to do synth

03:27

That's why he choose dfo

what the hell is M60

It's m30

03:28

Not m60

03:28

Sorry

03:28

Works same as dfo

weird

M30 is a potent iron chelator, radical scavenger and brain selective irreversible MAO-A and B inhibitor, with little inhibition of peripheral MAO

03:30

It has neuroprotective activity in in vitro and in vivo models of PD and unlike selective MAO-B inhibitors it increases brain dopamine, serotonin and noradrenaline. These findings indicate beside its anti PD action, it may also possess antidepressant activity, similar to selective MAO-A and nonselective MAO inhibitors. These properties make it an ideal anti PD drug for which it is being developed.

03:31

M30 would have been better option than dfo because it's mao inhibitor too

irreversible nonselective MAO inhibitors are deep in history for a reason

machineyadav

M30 would have been better option than dfo because it's mao inhibitor too

if that's the reasoning just add phenelzine to DFO

veganpermanently

if that's the reasoning just add phenelzine to DFO

Hmmmmmmmmm

03:34

M30 might be better because it has little actions on peripheral mao

machineyadav

M30 might be better because it has little actions on peripheral mao

that's a good thing, but MAO inhibition is redundant in PD treatment

03:40

it just goes to speak how little common sense is applied in drug design and how little faith in evolution these people have

03:41

MAO is inside the neuron for a reason

03:41

and the issue is not MAO, the issue is that there are monoamines in the cytosol in the first place

03:41

and this is because VMAT2 isn't functional

03:42

u know what happens if you KO VMAT2 and MAO at the same time

03:42

IMMENSE damage very quickly

Does COMT generate more toxic metabolites than MAO?

but if you overexpress VMAT2 the mice are immune to PD without MAO inhibition

machineyadav

Does COMT generate more toxic metabolites than MAO?

no it's autoxidation

03:43

it's the reason MAO exists. it produces less damage compared to autoxidation which is the property of entropy itself

The autoxidation and monoamine oxidase (MAO)-mediated metabolism of dopamine (3-hydroxytyramine; DA) cause a continuous production of hydroxyl radical (*OH), which is further enhanced by the presence of iron (ferrous iron, Fe(2+) and ferric ion, Fe(3+)).

03:45

Sussy iron

03:48

Image attachment

03:49

VMAT2 takes away dopamine even before getting oxidated

03:49

Very cool

03:49

One shouldn't miss modafinil if they have dopaminergic stack

03:51

Can't find any study on modafinil effects on vmat2

03:52

The most striking finding was that DAT knockout mice were completely unresponsive to the wake-promoting effects of methamphetamine, GBR-12909, and modafinil.

03:52

Interestingly, DAT knockout animals were also found to be more sensitive to caffeine,11 suggesting functional interactions between adenosinergic and DA systems in the control of sleep and wakefulness (see Caffeine section).

machineyadav

VMAT2 takes away dopamine even before getting oxidated

dopamine oxidation, be it MAO or autoxidation is dependent on 1. Vesicular loading failure which is VMAT2 availability and velocity 2. Iron availability 3. Last but definitely not the least, light exposure

04:10

improve any one of these aspects and dopaminergic degeneration doesn't happen at all. but if you take away iron or light to this point, tyrosine hydroxylase can't be activated thus there's no dopaminergic activity even tho the neurons are alive and well

04:11

my strategy is to increase VMAT2 as much as possible and keep in mind this will be detrimental to low IQ individuals, it will lead to delusion and shizophrenia, while high IQ might become bipolar depending on mitochondrial health

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1

04:11

reduce iron a little bit. veganism goes a long way

04:11

also reduce light exposure as much as possible

DFO also helps dopaminergic function afaik. It's already shipped but I expect some months. Weird it takes so long to ship to Asia

machineyadav

DFO also helps dopaminergic function afaik. It's already shipped but I expect some months. Weird it takes so long to ship to Asia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120698/

The desferrioxamine-prochlorperazine coma—clue to the role of dopam...

04:23

unrelated but interesting case study

Interesting

machineyadav

Interesting

While we're talking about this the H2O2 produced from the MAO reaction is not necessarily bad. Yes in large amounts it's a neurotoxin, but in small amounts it stimulates mitochondrial biogenesis via hormesis. If VMAT2 is functional and well expressed I think inhibiting MAO would not produce a healthier brain

05:13

if it's not functional, it's gonna do a lot of damage.

What is low dose in those context? I was using 300mg (in capryliic acid) for a while (NOW) I prefer jiagoulan/gymostemma for the most part, berberine seems to be a bit too cholinergic at times for me (subjectively, could be other effects) Also slightly concerned regarding it propensity for inducing double-strand DNA breaks, though I intuitively feel like this risk was probably overblown

So MAO inhibition only helps if brain health is somewhat compromised which is illustrated by the fact that MAO inhibitors are completely ineffective in advanced stage Parkinson's.

Odder_Sea (Glowie)

What is low dose in those context? I was using 300mg (in capryliic acid) for a while (NOW) I prefer jiagoulan/gymostemma for the most part, berberine seems to be a bit too cholinergic at times for me (subjectively, could be other effects) Also slightly concerned regarding it propensity for inducing double-strand DNA breaks, though I intuitively feel like this risk was probably overblown

I use 30 mg from extract - exact amount might be higher

05:15

also there might be more effective forms in there like dihydroberberine since it's a natural extract

05:15

it's standardized to 10 mg per pill. I take 5 per day

05:15

3 in the day mostly after lunch 2 before sleep

machineyadav

Click to see attachment 🖼️

Source

veganpermanently

dopamine oxidation, be it MAO or autoxidation is dependent on 1. Vesicular loading failure which is VMAT2 availability and velocity 2. Iron availability 3. Last but definitely not the least, light exposure

How does light exposure play into neuromelanin accumulation?

Yana

How does light exposure play into neuromelanin accumulation?

it catalyzes the reaction. mice kept in the dark don't accumulate neuromelanin

07:45

they also have increased lifespan dramatically and decreased locomotion. the locomotion can be recovered with short bursts of red light without detriment to lifespan

Yana

Source

Don't have

08:58

I searched dopamine autoxidation and clicked every link

veganpermanently

I use 30 mg from extract - exact amount might be higher

That seems really low, is that in capsules?

veganpermanently

also there might be more effective forms in there like dihydroberberine since it's a natural extract

I think Dihydroberberine is a very good form. I have a bottle, but haven't used it yet.

Pax1l

We report that, despite a larger muscle mass relative to age-matched wild types, there was no increase in maximum tetanic force generation, but that when expressed as a function of muscle size (specific force), muscles of myostatin-deficient mice were weaker than wild-type muscles

TB500 is a synthetic version of the healing protein released by the thymus gland (Thymosin Beta 4), also upregulates actin and myosin which open blood vessel pathways resulting in increased stamina and greater potential muscle growth. https://www.frontlinealternative.com/what-you-should-know-about-tb-500

What you should know about TB500 | Frontline Alternative Medicine

Frontline Alternative medicine explores the questions, What is BPC157? How does BPC157 work? and What are other Benefits of BPC157?

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