4029 replies to this topic

[lostfalco]

Hi lostfalco

 

I've been looking around for hydrogen water generators. Do you know any that are true to producing hydrogen rich water? I'd love to try some.

 

Best regards.

Hey yada, good to hear from you. I have this bad boy. http://www.amazon.co.../dp/B00FBSST8G/

 

It's difficult for me to recommend it because the price is so high and the effects are subtle (placebo?). I love the research on hydrogen water though and if the machine was around $200 then I would be much more likely to endorse it. 

 

[cylack]

Anyone using spaced learning (20/10/20/10/20)? I tried it yesterday for the first time during my study for the USMLE Step 2 CK (medical boards). I'm using these review videos, which are about 20 mins in duration so perfect length for the "input". As for the 10 minute distractors, I would use an adult coloring book which had mandala designs. Sometimes I would do light physical activity like walking around my apartment complex.

 

The one question I have is, should I be using the exact same input? That is, should I be watching the same video 3x or should I be "manipulating/working with" the information in the video, like making flashcards? What I did yesterday was watch the video for my first input, make flashcards (in Cerego so I can use them later for spaced repetition) for my second input, and go over the flashcards for my third input. This was what was suggested in the spaced learning guidebook (http://www.innovatio...nloadable_1.pdf). In the guidebook which was geared to school teachers, it said the first input should be presentation where the teacher lectures and shows powerpoint slides to the students, the second input focuses on recall so students might be showed the same powerpoints now missing keywords, and the third input focuses on understanding so students should carry out a task that applies the knowledge or skills they have just acquired, perhaps by taking a quiz.

 

Here is a newspaper article describing how SL was used at the high school in England where it was developed: http://www.theguardi.../gcses-teaching

 

I have to admit, when recalling information I studied yesterday it isn't rock solid, so I'm wondering if I should switch things up and just watch the exact same video 3x. Falco or anyone else using this, I would be interested in your feedback. Thanks.

 

 

Edited by cylack, 28 January 2016 - 06:28 PM.

[lostfalco]

Anyone using spaced learning (20/10/20/10/20)? I tried it yesterday for the first time during my study for the USMLE Step 2 CK (medical boards). I'm using these review videos, which are about 20 mins in duration so perfect length for the "input". As for the 10 minute distractors, I would use an adult coloring book which had mandala designs. Sometimes I would do light physical activity like walking around my apartment complex.

 

The one question I have is, should I be using the exact same input? That is, should I be watching the same video 3x or should I be "manipulating/working with" the information in the video, like making flashcards? What I did yesterday was watch the video for my first input, make flashcards (in Cerego so I can use them later for spaced repetition) for my second input, and go over the flashcards for my third input. This was what was suggested in the spaced learning guidebook (http://www.innovatio...nloadable_1.pdf). In the guidebook which was geared to school teachers, it said the first input should be presentation where the teacher lectures and shows powerpoint slides to the students, the second input focuses on recall so students might be showed the same powerpoints now missing keywords, and the third input focuses on understanding so students should carry out a task that applies the knowledge or skills they have just acquired, perhaps by taking a quiz.

 

Here is a newspaper article describing how SL was used at the high school in England where it was developed: http://www.theguardi.../gcses-teaching

 

I have to admit, when recalling information I studied yesterday it isn't rock solid, so I'm wondering if I should switch things up and just watch the exact same video 3x. Falco or anyone else using this, I would be interested in your feedback. Thanks.

Hey cylack, I've found it beneficial to watch the same video 3x with a pad of paper next to me and furiously jot down ideas that stand out to me as I'm watching the video (it's important to 'generate' ideas and not just passively watch). I usually don't make my Anki flashcards until after I've finished all three sets of 20/10. That seems to work for me but...gulp, here it comes...ymmv. 

[cylack]

Falco, cool thanks. I switched it up yesterday just watching the same video 3x and doing the flaschcards afterwards just like you do and it seems to be working better.

 

BTW, saw on another thread that in the past you had ordered Cerluten brain peptide from anti-aging systems. How was the Cerluten, any noticeable benefits? I get a lot of mail from anti-aging systems touting Cerluten's benefits but all the research is from Russia from the same scientist.

 

[lostfalco]

Falco, cool thanks. I switched it up yesterday just watching the same video 3x and doing the flaschcards afterwards just like you do and it seems to be working better.

 

BTW, saw on another thread that in the past you had ordered Cerluten brain peptide from anti-aging systems. How was the Cerluten, any noticeable benefits? I get a lot of mail from anti-aging systems touting Cerluten's benefits but all the research is from Russia from the same scientist.

Very cool. Glad that seems to be helping, cylack. 

 

I had the most noticeable results from pinealon, surprisingly. Nuke tried it recently (along with cortagen) as well and it seemed to help his stroop test scores on cambridgebrainsciences. http://www.longecity...en/#entry759895

 

I'm with you though...the research is pretty much ALL from Khavinson. I bit the bullet and tried them despite my reservations and was pretty surprised that I noticed anything. I'll revisit them within the next few years but for now we have some pretty cool enhancements to test out that are quite a bit more affordable. 

[cylack]

So I used to do this when I was younger, but I was surprised to see there is actually scientific benefit to it. It is being called "super brain yoga" now. Apparently it helps to synchronize the whole brain and improve focus and attention. In the video I linked a Yale researcher talks about it and an MD tells his patients to do it. It only takes a minute to do.  Amazing that the Indian rishis knew all this thousands of years ago:

 

https://www.youtube....h?v=KSwhpF9iJSs

[lostfalco]

For introductory neuroscience info I like some of Baylor University Neuroscientist David Eagleman's work. He did a six part introduction to the brain with the BBC and here's one of the episodes. Enjoy!

 

Eagleman's book: http://www.amazon.co.../dp/0307389928/

 

BBC series: http://www.bbc.co.uk...rammes/b06y8hyr

 

Edited by lostfalco, 31 January 2016 - 03:50 PM.

[Nuke]

Thanks Falco. Like always this thread is a goldmine of info.

 

I'm currently doing my research on LLLT. I found these LEDs. What I like its that they are 830nm, that is closer to the 820nm absorption peak. I'm thinking on building an array with those and a piece of strip board. They are also not much more expensive than 850nm LED I have seen.

 

While busy with the electron transport chain, I'm also trying to learn more on the MOA of Methylene Blue. While it seems that using LLLT is not a good idea with MB in your system, doing LLLT and then taking MB should be safe. What I'm trying to figure out is if LLLT+MB+C60oo+CoQ10+PQQ is both effective and safe. My biggest issue is that we know far too little about C60oo's MOA. I have a feeling that it may also play a role in the electron transport chain, more than just acting as an anti-oxidant. That would explain the effect of C60 on exercise.

 

For interest sake, I got a quote for Vanadyl Sulphate from my lab supplier. Its pretty expensive at around R1700($100) per 25g.

 

For those who have not checked my peptide thread, my Rotations score had an even bigger increase than the Stroop test. No effect on working memory though. Subjectively my memory feels better, if I see a number and I repeat it a few times, I can remember it easier. But I have no tests on that.

 

[lostfalco]

So I used to do this when I was younger, but I was surprised to see there is actually scientific benefit to it. It is being called "super brain yoga" now. Apparently it helps to synchronize the whole brain and improve focus and attention. In the video I linked a Yale researcher talks about it and an MD tells his patients to do it. It only takes a minute to do.  Amazing that the Indian rishis knew all this thousands of years ago:

 

https://www.youtube....h?v=KSwhpF9iJSs

Thanks for the video, cylack (I'll try take a look when I have some time). I'm admittedly skeptical but I like to follow the data wherever it goes (no matter how counterintuitive). I'll try to look deeper into this whenever I get a chance. I glanced at some of the ideas a year or so ago. I do think there are HUGE mental enhancement opportunities related to hub node/brain network/default mode network optimization (prefrontal, parietal/precuneus, cingluate, etc.) so if it has some measurable impacts there then I'm def interested. 

[lostfalco]

Thanks Falco. Like always this thread is a goldmine of info.

 

I'm currently doing my research on LLLT. I found these LEDs. What I like its that they are 830nm, that is closer to the 820nm absorption peak. I'm thinking on building an array with those and a piece of strip board. They are also not much more expensive than 850nm LED I have seen.

 

While busy with the electron transport chain, I'm also trying to learn more on the MOA of Methylene Blue. While it seems that using LLLT is not a good idea with MB in your system, doing LLLT and then taking MB should be safe. What I'm trying to figure out is if LLLT+MB+C60oo+CoQ10+PQQ is both effective and safe. My biggest issue is that we know far too little about C60oo's MOA. I have a feeling that it may also play a role in the electron transport chain, more than just acting as an anti-oxidant. That would explain the effect of C60 on exercise.

 

For interest sake, I got a quote for Vanadyl Sulphate from my lab supplier. Its pretty expensive at around R1700($100) per 25g.

 

For those who have not checked my peptide thread, my Rotations score had an even bigger increase than the Stroop test. No effect on working memory though. Subjectively my memory feels better, if I see a number and I repeat it a few times, I can remember it easier. But I have no tests on that.

Thanks, man. I've learned a ton from everyone who has posted on the thread as well. 

 

Zawy has some great info on building LLLT devices and is an excellent resource if you want to try to contact him. http://heelspurs.com/led.html

 

Dr. Gonzalez-Lima seemed to think that MB combined with LLLT would be just fine (per email correspondence).

 

C60 seems a bit risky to me. The research was all over the place when I took a look at it 2 months ago. I know a lot of people seem to do pretty well on it here on Longecity but I'm still a bit hesitant to add it to my regimen. I'll take another look at it in a few months and see if any new data has come out. 

 

Yeah, that vanadyl sulphate is a bit pricey...but not too outrageous. Low dose Vanadium is reasonably priced and may be worth trying first just to see if there is any additive benefit with intranasal insulin. 

 

Thanks for adding your Rotations data too! That's very cool. I've never taken cortagen. Looks like awakebrain sells a powder and suggests intranasal dosing. Interesting. Gonna have to research this. http://awakebrain.com/cortagen-powder/

 

They have pinealon powder as well. http://awakebrain.com/pinealon-powder/

 

...and nasal spray bottles. http://awakebrain.co...-spray-bottles/

 

You took your peptides (with tfa removed) intranasally as well, right Nuke?  

Edited by lostfalco, 01 February 2016 - 12:34 AM.

[Nuke]

That website(heelspurs) is awesome, I'm using it as one of my main references. He really did his research.

 

Did Dr. Gonzalez-Lima give any more technical details on why it would be fine?

 

I agree that C60 is very experimental, but I'm taking a small amount compared to many members here. Was using 1.6mg a day, going to drop it to 0.5mg a day in my next batch. The people taking 20mg+ a day will run into issues long before I do. I also waited 3 years before I started it, doing almost a year worth of research. I'm also making it myself with 99.95& C60, to be more sure of the quality. Now is the first time I really started to worry about interactions, seeing that TULIP targets the mitocondria. I'll keep you posted.

 

Talking about mitocondrial enhancement, how about focusing on the rest of the Kreb cycle? AFAIK isocitrate dehydrogenase is the rate limiting step, maybe we can do something about that? Just a random thought while I'm at work.

 

I was planning on adding Vanadium to my stack in anyway, more as precaution than to as a nootropic. But if it can double as both, its awesome.

 

The funny thing about Rotations the first 2 times was, I thought I was doing very badly. I take even less than what awakebrain recommends. I got mine from Genscript, that way I can be sure about the quality. Internasal dosing works fine for me. Mixed it with saline and a little alcohol. Alcohol in the nose may not be the best idea, but its only a very small amount, so I decided to risk it.

 

[Reformed-Redan]

Does hair block out the effects of LLLT? 

 

I've been focusing on the DLPFC and so far have nothing but good things to say about it. Are there specific areas to focus on to maximize effects? I wish there was a FAQ on what areas to target for what purposes. I feel like those interested in treating depression should only focus on the DLPFC(?) Am I correct here?

 

Thanks for this awesome thread LF!

[lostfalco]

 

That website(heelspurs) is awesome, I'm using it as one of my main references. He really did his research.

 

Did Dr. Gonzalez-Lima give any more technical details on why it would be fine?

 

Talking about mitocondrial enhancement, how about focusing on the rest of the Kreb cycle? AFAIK isocitrate dehydrogenase is the rate limiting step, maybe we can do something about that? Just a random thought while I'm at work.

 

I was planning on adding Vanadium to my stack in anyway, more as precaution than to as a nootropic. But if it can double as both, its awesome.

 

The funny thing about Rotations the first 2 times was, I thought I was doing very badly. I take even less than what awakebrain recommends. I got mine from Genscript, that way I can be sure about the quality. Internasal dosing works fine for me. Mixed it with saline and a little alcohol. Alcohol in the nose may not be the best idea, but its only a very small amount, so I decided to risk it.

 

Yeah, Scott Roberts/zawy and I have had some great conversations over the years. 

http://www.longecity...e-5#entry585474

http://www.longecity...biophysics-etc/

 

He discussed it a little (he is one of the world's leading experts on MB and LLLT). BieraK actually did the (appreciated) legwork and emailed him. His posts start here.http://www.longecity...-80#entry727412

 

There are a LOT of other possible supplements to add that we've talked about: B vitamins, Vitamin K, Magnesium, Creatine, ALCAR, ALA, niagen, epicatechin, mitoQ, ursolic acid, intranasal insulin (enhances brain mitochondrial function), etc. If you find some other interesting ones let me know!

 

I've got a little Vanadium lying around. I may try adding 5mg here or there to see if I notice anything. I think historically it was dosed in the 100mg range for diabetics. 

 

It's very interesting that Pinealon/Cortagen seemed to help Stroop and Rotations scores but not other measures. That's what I love about experiments though. They almost never turn out how I think they will. 

 

 

 

 

Edited by lostfalco, 02 February 2016 - 12:35 PM.

[lostfalco]

Does hair block out the effects of LLLT? 

 

I've been focusing on the DLPFC and so far have nothing but good things to say about it. Are there specific areas to focus on to maximize effects? I wish there was a FAQ on what areas to target for what purposes. I feel like those interested in treating depression should only focus on the DLPFC(?) Am I correct here?

 

Thanks for this awesome thread LF!

No problem, redan. Glad you've found some helpful info!

 

I'd say the dlpfc is definitely the priority but theoretically and in my experience, I think whole brain is the way to go (even for mood/depression). Our brain is made up of interactive, complementary hub nodes that network with one another and jointly contribute to cognition. The more we can enhance mitochondria in all regions, the better imo. Hair does block the light so I recommend that you take the glass cover off of the 96 LED unit and 'nestle' the lights past your hair and onto your scalp. I actually press down pretty hard against my skin to enhance penetration depth. Of course, experiment with different things and see what works best for you but my guess is that you'll see the best results with whole brain LLLT. 

[lostfalco]

"Study the Bird, Not the Words"

 

"You can know the name of a bird in all the languages of the world, but when you're finished, you'll know absolutely nothing whatever about the bird... So let's look at the bird and see what it's doing -- that's what counts. I learned very early the difference between knowing the name of something and knowing something." --Richard Feynman

 

Application for us: I've found it extremely helpful to watch as many videos and look at as many pictures as possible when studying neuroscience and ways to enhance my brain. I like to call it "The Feynman Principle". I would humbly recommend it to everyone starting out in their enhancement journeys. A picture is worth a thousand words...a video is worth a billion. Be safe! =)

 

Edited by lostfalco, 02 February 2016 - 10:56 PM.

[Jochen]

something for your LostFalco :-)

 

http://www.ncbi.nlm....pubmed/26829513

 

Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8.

Nakai M^1,2, Iizuka M², Matsui N³, Hosogi K¹, Imai A², Abe N^1,2, Shiraishi H^1,2, Hirata A^1,2, Yagi Y^1,2, Jobu K², Yokota J², Kato E⁴, Hosoda S⁴, Yoshioka S³, Harada K³, Kubo M³, Fukuyama Y³, Miyamura M^1,2.

Author information

Abstract

Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

KEYWORDS:

Bangle (Zingiber purpureum); Ki67; SAMP8; neurogenesis; neurotrophic activity; spatial learning and memory

 

[lostfalco]

 

something for your LostFalco :-)

 

http://www.ncbi.nlm....pubmed/26829513

 

Thanks, Jochen! I do love neurogenesis so I'll take a look. 

[Reformed-Redan]

lostfalco, I sent you an invite for an already reserved spot for you in the NRX-1074 group buy thread. If interested let me know. Just check the research on it! Those rats were super-rats after treatment with NRX-1074 from what I've seen.

 

Cheers.

[lostfalco]

lostfalco, I sent you an invite for an already reserved spot for you in the NRX-1074 group buy thread. If interested let me know. Just check the research on it! Those rats were super-rats after treatment with NRX-1074 from what I've seen.

 

Cheers.

Thanks for the invite, yada! Unfortunately, I've pretty much spent all I can afford on intranasal insulin, peptides, clonidine (I couldn't find guanfacine...any reliable sources?), ghrelin mimetics, etc. I'm currently whittling everything down to only the barest essentials in order to make things financially sustainable for me. I appreciate the thought though! I look forward to seeing how everything progresses for you guys. 

[cylack]

Nice find. According to wiki,  another name for Zingiber purpureum is Zingiber cassumunar. Anyone find any edible sources? Ebay lists a lot of powders but they seem meant for topical skin use.

 

 

something for your LostFalco :-)

 

http://www.ncbi.nlm....pubmed/26829513

 

Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8.

Nakai M^1,2, Iizuka M², Matsui N³, Hosogi K¹, Imai A², Abe N^1,2, Shiraishi H^1,2, Hirata A^1,2, Yagi Y^1,2, Jobu K², Yokota J², Kato E⁴, Hosoda S⁴, Yoshioka S³, Harada K³, Kubo M³, Fukuyama Y³, Miyamura M^1,2.

Author information

Abstract

Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

KEYWORDS:

Bangle (Zingiber purpureum); Ki67; SAMP8; neurogenesis; neurotrophic activity; spatial learning and memory

 

 

Edited by cylack, 03 February 2016 - 07:38 AM.

[Reformed-Redan]

 

lostfalco, I sent you an invite for an already reserved spot for you in the NRX-1074 group buy thread. If interested let me know. Just check the research on it! Those rats were super-rats after treatment with NRX-1074 from what I've seen.

 

Cheers.

Thanks for the invite, yada! Unfortunately, I've pretty much spent all I can afford on intranasal insulin, peptides, clonidine (I couldn't find guanfacine...any reliable sources?), ghrelin mimetics, etc. I'm currently whittling everything down to only the barest essentials in order to make things financially sustainable for me. I appreciate the thought though! I look forward to seeing how everything progresses for you guys. 

 

In order to obtain guanfacine, I had to contact suppliers from Alibaba and eventually found one. The quality was high and effects very noticeable. It's a great nootropic IMHO.

[lostfalco]

In order to obtain guanfacine, I had to contact suppliers from Alibaba and eventually found one. The quality was high and effects very noticeable. It's a great nootropic IMHO.

 

 

Very cool. Thanks, man. Clonidine was much easier to find so I'm gonna give that a go first before I try guanfacine. I'm pretty much attempting to simultaneously hit every mechanism Arnsten mentions in layer iii of the dorsolateral prefrontal cortex (using low doses). It seems to be working pretty damn well so far. 

 

 

 

 

http://www.ncbi.nlm....les/PMC4734124/

 

Annu Rev Pharmacol Toxicol. 2016 Jan 6;56:339-60. doi: 10.1146/annurev-pharmtox-010715-103617.

Targeting Prefrontal Cortical Systems for Drug Development: Potential Therapies for Cognitive Disorders.

Arnsten AF1, Wang M1.

Author information

Abstract

Medications to treat cognitive disorders are increasingly needed, yet researchers have had few successes in this challenging arena. Cognitive abilities in primates arise from highly evolved N-methyl-d-aspartate (NMDA) receptor circuits in layer III of the dorsolateral prefrontal cortex. These circuits have unique modulatory needs that can differ from the layer V neurons that predominate in rodents, but they offer multiple therapeutic targets. Cognitive improvement often requires low doses that enhance the pattern of information held in working memory, whereas higher doses can produce nonspecific changes that obscure information. Identifying appropriate doses for clinical trials may be helped by assessments in monkeys and by flexible, individualized dose designs. The use of guanfacine (Intuniv) for prefrontal cortical disorders was based on research in monkeys, supporting this approach. Coupling our knowledge of higher primate circuits with the powerful methods now available in drug design will help create effective treatments for cognitive disorders.

 

 

http://www.ncbi.nlm....pubmed/26646567

 

Dongwuxue Yanjiu. 2015 Nov 18;36(6):314-8.

Physiological approaches to understanding molecular actions on dorsolateral prefrontal cortical neurons underlying higher cognitive processing.

Wang M1, Arnsten AF2.

Author information

Abstract

Revealing how molecular mechanisms influence higher brain circuits in primates will be essential for understanding how genetic insults lead to increased risk of cognitive disorders. Traditionally, modulatory influences on higher cortical circuits have been examined using lesion techniques, where a brain region is depleted of a particular transmitter to determine how its loss impacts cognitive function. For example, depletion of catecholamines or acetylcholine from the dorsolateral prefrontal cortex produces striking deficits in working memory abilities. More directed techniques have utilized direct infusions of drug into a specific cortical site to try to circumvent compensatory changes that are common following transmitter depletion. The effects of drug on neuronal firing patterns are often studied using iontophoresis, where a minute amount of drug is moved into the brain using a tiny electrical current, thus minimizing the fluid flow that generally disrupts neuronal recordings. All of these approaches can be compared to systemic drug administration, which remains a key arena for the development of effective therapeutics for human cognitive disorders. Most recently, viral techniques are being developed to be able to manipulate proteins for which there is no developed pharmacology, and to allow optogenetic manipulations in primate cortex. As the association cortices greatly expand in brain evolution, research in nonhuman primates is particularly important for understanding the modulatory regulation of our highest order cognitive operations.

 

Edited by lostfalco, 03 February 2016 - 01:46 PM.

[lostfalco]

Interesting. Testosterone increases pgc1-a, increases mitochondrial biogenesis, increases oxphos, decreases ROS, increases insulin sensitivity. Nasal testosterone doubles rodent levels of brain testosterone. Hmmm....

 

http://totallyyu.com...dysfunction.pdf

 

T increases PGC-1α expression [33, 46, 47, 56], which in turn increases Tfam expression [46] as well as mitochondrial biogenesis [46]. The increase in mitochondrial biogenesis increases levels of NRF-1 [46], which in turn increases oxidative phosphorylation [7, 33]. T increases Tfam expression as well as Akt phosphorylation [46], both of which decrease apoptosis leading to an increase in oxidative phosphorylation. T stimulates lipolysis and down-regulates lipoprotein lipase (LPL) activity [36, 37] and increases expression of FABP [48] leading to an increase in fatty acid oxidation and in oxidative phosphorylation [33, 46, 48]. T increases expression of PDH [49], which increases production of OAA and acetyl-CoA [49] leading to a stimulation of the TCA. T also increases expression of SDH and aconitase [50], also up-regulating TCA and increasing oxidative phosphorylation [33, 46, 48, 50]. Finally, T increases the expression of cytochrome c oxidase [9, 48, 73], which leads to an increase in oxidative phosphorylation. The increase in oxidative phosphorylation leads to a decrease in ROS and an increase in insulin sensitivity [74]. 

 

 Screen Shot 2016-02-03 at 9.27.20 AM.png   253.35KB   8 downloads

 

 

http://www.ncbi.nlm....pubmed/25961343

 

Horm Mol Biol Clin Investig. 2011 Oct 1;8(1):431-44. doi: 10.1515/HMBCI.2011.132.

Androgen deficiency and mitochondrial dysfunction: implications for fatigue, muscle dysfunction, insulin resistance, diabetes, and cardiovascular disease.

Traish AM, Abdallah B, Yu G.

Abstract

Among the major physiological functions of steroid hormones is regulation of carbohydrate, fat, and protein metabolism. Mitochondria, through oxidative phosphorylation, play a critical role in modulating a host of complex cellular metabolic pathways to produce chemical energy to meet the metabolic demand for cellular function. Thus, androgens may regulate cellular metabolism and energy production by increased mitochondrial numbers, activation of respiratory chain components, and increased transcription of mitochondrial-encoded respiratory chain genes that code for enzymes responsible for oxidative phosphorylation. Androgen deficiency is associated with increased insulin resistance, type 2 diabetes (T2DM), metabolic syndrome, obesity, and increased overall mortality. One common link among all these pathologies is mitochondrial dysfunction. Contemporary evidence exists suggesting that testosterone deficiency (TD) contributes to mitochondrial dysfunction, including structural alterations and reduced expression and activities of metabolic enzymes. Here, we postulate that TD contributes to symptoms of fatigue, insulin resistance, T2DM, cardiovascular risk, and metabolic syndrome through a common mechanism involving impairment of mitochondrial function.

 

 

Edited by lostfalco, 03 February 2016 - 03:37 PM.

[lostfalco]

Guinness Push-Ups World Record: 2,220 in One Hour

 

On July 25, 2015, Carlton Williams (UK) set the world record for most push ups in an hour. When I saw this headline I thought, "Holy crap, I can't believe this guy can do push ups for an entire hour straight!" And then...I watched the video....

 

https://youtu.be/DbwZ89yq_Aw?t=1m59s

 

 

Application for us: The way Carlton does push-ups is the way I've found most effective for studying. I study in bursts of 20 minutes and then rest for 10 minutes (sometimes I do 10 and 5). When I do this I find it VERY easy to study for an entire day. It's just not that tiring. The hard part is actually the resting! It's so easy for me to become impatient or to try to get something done. However, resting forces me to be quiet, still my mind, and refocus myself. Try some variations on this theme (work for 25 min, rest for 5) and see if you can find a method what works well for you. Your blood pressure, heart rate, and stress levels with thank you for it. =)

 

Edited by lostfalco, 08 February 2016 - 03:43 PM.

[Lsdium]

Application for us: The way Carlton does push-ups is the way I've found most effective for studying. I study in bursts of 20 minutes and then rest for 10 minutes (sometimes I do 10 and 5). When I do this I find it VERY easy to study for an entire day. It's just not that tiring. The hard part is actually the resting! It's so easy for me to become impatient or to try to get something done. However, resting forces me to be quiet, still my mind, and refocus myself. Try some variations on this theme (work for 25 min, rest for 5) and see if you can find a method what works well for you. Your blood pressure, heart rate, and stress levels with thank you for it. =)

 

What type of burst are you doing? 

 

Are the vib-plate also included in your bursting? 

[lostfalco]

What type of burst are you doing? 

 

 

 

 

Are the vib-plate also included in your bursting?  

 

 

Always

 

 

[lostfalco]

Rolipram activates proteosomes, clears out unwanted brain proteins. 

 

Other PDE4i that is less likely to cause projectile vomiting (do not take rolipram!): ibudilast (zembrin might be another possibility). 

https://en.wikipedia.../wiki/Ibudilast

http://www.ncbi.nlm....pubmed/19032723

Where to buy ibudilast: http://www.mimaki-fa...roduct_id=35376

Where to buy zembrin: http://www.iherb.com...lets/52618/?p=1

 

I have some ibudilast and I may try to take it before bed and see what happens. Anyone try this?

 

I've had very good results taking autophagy enhancers right before bed (spermidine, longvida curcumin, etc.) http://www.ncbi.nlm....pubmed/25526088

 

 

 

 

http://www.nature.co...ll/nm.4011.html

 

Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling

 

Abstract

The ubiquitin proteasome system (UPS) degrades misfolded proteins including those implicated in neurodegenerative diseases. We investigated the effects of tau accumulation on proteasome function in a mouse model of tauopathy and in a cross to a UPS reporter mouse (line Ub-G76V-GFP). Accumulation of insoluble tau was associated with a decrease in the peptidase activity of brain 26S proteasomes, higher levels of ubiquitinated proteins and undegraded Ub-G76V-GFP. 26S proteasomes from mice with tauopathy were physically associated with tau and were less active in hydrolyzing ubiquitinated proteins, small peptides and ATP. 26S proteasomes from normal mice incubated with recombinant oligomers or fibrils also showed lower hydrolyzing capacity in the same assays, implicating tau as a proteotoxin. Administration of an agent that activates cAMP–protein kinase A (PKA) signaling led to attenuation of proteasome dysfunction, probably through proteasome subunit phosphorylation. In vivo, this led to lower levels of aggregated tau and improvements in cognitive performance.

 

 

"Of particular note in the present study was the ability of a pharmacological agent to promote proteasome activity, reduce tau and ameliorate disease-associated cognitive defects through cAMP-PKA signaling in mice during early-stage disease. However, short-term cAMP-PKA activation in mice at later stages of disease did not have the same effect. It is possible that this was a result of the short (3-week) exposure to rolipram or of suboptimal dosing of the mice, which have a very robust tauopathy phenotype. Alternatively, the form of tau cleared by the UPS might be the form involved in cell-to-cell propagation of tauopathy, and prevention of propagation of this form of tau by rolipram might be apparent only in a mouse model, where propagation of the disease can be quantified^41, 42.

 

We have shown that enhanced cAMP-PKA signaling in vivo leads to phosphorylation of several proteins in purified proteasomes leading to and that phosphorylation of critical proteasome subunits (particularly Rpn6) enhanced peptide and conjugate breakdown and ATPase function³². cAMP and PKA activate many other cellular processes, but enhancement of protein breakdown by phosphorylation of the proteasome is a new action for cAMP signaling.

Together, these findings point to enhancement of proteasomal function through agents that phosphorylate proteasome subunits as a potentially promising therapeutic approach to treatment of proteotoxic diseases."

Edited by lostfalco, 09 February 2016 - 12:57 PM.

[bigyellowlemon]

https://en.wikipedia.org/wiki/Apigenin Apigenin induces autophagy. It is a benzo-site ligand at the GABA-A receptor, being a PAM. It also binds to the adenosine receptor, as well as being an NMDA antagonist. It is also neurogenic. The only negative I can think of is that it is anti-inflammatory, which might not be good for sleep.

 

I would strongly suggest not taking PDE4i at night time, from my understanding that would destroy circadian signaling and rhythm. Curcumin, though a wonderful substance, would not be good for sleep either. 

 

Spermidine seems good at night.

 

Maybe take PDE4i and curcumin in morning and spermidine and apigenin at night? Of course we could add more as well.

 

EDIT: Apigenin also actiavtes monoamine transporters so it can blunt drive and salience, good for sleep. 

Edited by bigyellowlemon, 09 February 2016 - 01:30 AM.

[lostfalco]

A brief reminder on the recently (2013ish) discovered glymphatic system. 

 

 

 

http://www.ncbi.nlm....pubmed/26690495

 

J Cereb Blood Flow Metab. 2015 Dec 21. pii: 0271678X15622047. [Epub ahead of print]

Ultra-fast magnetic resonance encephalography of physiological brain activity - Glymphatic pulsation mechanisms?

Kiviniemi V1, Wang X2, Korhonen V3, Keinänen T3, Tuovinen T3, Autio J4, LeVan P5, Keilholz S6, Zang YF7, Hennig J5, Nedergaard M8.

Author information

Abstract

The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in ≈1 Hz cycles. The respiratory ≈0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001-0.023 Hz) and low frequency (LF 0.023-0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases.

 

Edited by lostfalco, 09 February 2016 - 01:11 PM.

[lostfalco]

https://en.wikipedia.org/wiki/Apigenin Apigenin induces autophagy. It is a benzo-site ligand at the GABA-A receptor, being a PAM. It also binds to the adenosine receptor, as well as being an NMDA antagonist. It is also neurogenic. The only negative I can think of is that it is anti-inflammatory, which might not be good for sleep.

 

I would strongly suggest not taking PDE4i at night time, from my understanding that would destroy circadian signaling and rhythm. Curcumin, though a wonderful substance, would not be good for sleep either. 

 

Spermidine seems good at night.

 

Maybe take PDE4i and curcumin in morning and spermidine and apigenin at night? Of course we could add more as well.

 

EDIT: Apigenin also actiavtes monoamine transporters so it can blunt drive and salience, good for sleep. 

Which mechanisms are you thinking of with PDE4i and circadian biology? Ibudilast (mainly PDE4i) is a bit non-selective and PDE5i is pretty bad before bed so it may not be the best idea...but I'm curious. Took it last night (10mg) without any problems or noticeable positive effects. I'll try it again a few times and see what happens. 

 

Curcumin/turmeric seems to enhance some people and inhibit others before sleep (anecdotally). What are your reasons for advising against it? Glial cell activity? 

 

Anecdotally it works pretty well for me. Wake up refreshed with a clear head. 

 

Spermidine is quite good before bed ime. Been taking it for about a month and half so we'll see how it works over time. 

 

I've only taken apigenin during the day. I'll look into the mechanisms (there are always many) and see how it looks overall. Have you tried it before bed?

Edited by lostfalco, 09 February 2016 - 04:17 PM.