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Manipulating mitochondrial dynamics

nad nad+ c60 mito fission fusion stearic acid mtdna methylene blue

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#1381 QuestforLife

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Posted 10 May 2019 - 09:47 AM

That depends on how much damage you have. First the lysosomic capacity is limited, and second it's theoretically possible to have almost 100% damaged mtDNA loops in a cell and it still function fairly well (as multiple loops in a single mitochondrion cover for each other). In which case removing them all in an extended fission state prior to biogenesis could be difficult and probably dangerous. Better to for the body to take small steps rather than jump that chasm in a single bound.

 

Yes, I think this is what we can take from the study - they showed autophagy was actually harmful in the case where mitochondrial turnover (which requires fission) has been neglected for too long. 

 

I think of mitophagy as decommissioning a mini nuclear reactor - you want to minimise the leakage of nuclear waste into the rest of the cell. 

 

More generally there is a clear short term advantage to maintain large mitochondria - ATP production can be maintained even with substantial damage. But doing this for too long sends the cell down a path of no return. Whereas maintaining small mitochondria results in an immediate loss of ATP every time a mitochondrion sustains damage, but prevents long term decline of function and eventual loss of the cell.

 

Clearly the cell is not going to maintain small mitochondria when large amounts of ATP are required, but it is in the cell's advantage to do so when energy requirements are reduced. Hence autophagy should be carried out with the circadian rhythm of day and night time. 

 

I have been experimenting with 16:8 hour fasting:feeding windows, with autophagy inducers last thing at night and first thing in the morning (when still fasting). Whilst I haven't suddenly reverted from 40 to 20 years old, my mental acuity has improved, and I look rather good with my top off. 


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#1382 HighDesertWizard

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Posted 18 May 2019 - 05:46 AM

2018, Inhibitory modulation of cytochrome coxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury
 
The things to look for in this study, and the reason a first post about the details belongs in this forum thread, are the variable impacts different NIR frequencies have on cytochrome c oxidase expression. Here's the abstract...
 

The interaction of light with biological tissue has been successfully utilized for multiple therapeutic purposes. Previous studies have suggested that near infrared light (NIR) enhances the activity of mitochondria by increasing cytochrome c oxidase (COX) activity, which we confirmed for 810 nm NIR. In contrast, scanning the NIR spectrum between 700 nm and 1000 nm revealed two NIR wavelengths (750 nm and 950 nm) that reduced the activity of isolated COX. COX-inhibitory wavelengths reduced mitochondrial respiration, reduced the mitochondrial membrane potential (ΔΨm), attenuated mitochondrial superoxide production, and attenuated neuronal death following oxygen glucose deprivation, whereas NIR that activates COX provided no benefit. We evaluated COX-inhibitory NIR as a potential therapy for cerebral reperfusion injury using a rat model of global brain ischemia. Untreated animals demonstrated an 86% loss of neurons in the CA1 hippocampus post-reperfusion whereas inhibitory NIR groups were robustly protected, with neuronal loss ranging from 11% to 35%. Moreover, neurologic function, assessed by radial arm maze performance, was preserved at control levels in rats treated with a combination of both COX-inhibitory NIR wavelengths. Taken together, our data suggest that COX-inhibitory NIR may be a viable non-pharmacologic and noninvasive therapy for the treatment of cerebral reperfusion injury.

 
Wow! This is important. The details are worth grasping and I'll explain why in another post in another thread...
 
Keep in mind that most other studies of the benefits of NIR light focus on frequencies between 810 nm and 860 nm...
 
From the Results portion of the paper...
 

Identification of COX-inhibitory NIR

 

We systematically screened the NIR electromagnetic spectrum in the “therapeutic window of opportunity” of 700 nm to 1000 nm, where NIR absorptions by water and blood are minimal, allowing deep tissue penetration of the NIR for possible medical applications. We integrated a light-protected oxygen electrode chamber into a double beam spectrophotometer (see Materials and Methods), which contained regulatory-competent bovine COX purified under conditions preserving the physiological regulatory properties of the enzyme, such as posttranslational modifications (Fig. 1A). While the NIR frequencies were scanned, COX activity was measured simultaneously. In contrast to previous studies concluding that NIR consistently activates COX12,17,18,19,20,21,22, we identified two novel wavelength ranges (750 nm and 950 nm) that inhibit COX activity (Fig. 1B).

 

rIZzOIoh.png

 

Caption

 

NIR modulates COX activity and mitochondrial oxygen consumption rate. (A) Isolated regulatory-competent bovine COX separated into its subunits on a high-resolution urea/SDS-PAGE Coomassie-stained gel. Subunits are indicated in roman numerals. (B) Representative scan of wavelength-dependent COX activity identifying the 750 nm and 950 nm wavelength rages as inhibitory regions. © Effect of NIR emitted by LED diodes confirms that 750 nm and 950 nm NIR inhibit COX in vitro while 810 nm NIR activates the enzyme. Data were obtained over a 3-min interval of irradiation and normalized to non-irradiated samples (n ≥ 4; *p < 0.05). (D) NIR irradiation modulates oxygen consumption rate (OCR) in a wavelength specific manner. 750 nm and 950 nm NIR reduce OCR below the basal respiration rate and 810 nm NIR increase mitochondrial OCR (n ≥ 4; *p < 0.05).

 

 
 

From the study above we learn that different frequencies of Near InfraRed (NIR) light can either reduce or increase cytochrome c oxidase

  • Combined 750 and 950 nm NIR light exposure maximally inhibited cytochrome c oxidase expression
  • 810 nm NIR light exposure maximized cytochrome c oxidase expression
Why is that important?
 
  
2018, The Involvement of Cytochrome c Oxidase in Mitochondrial Fusion in Primary Cultures of Neonatal Rat Cardiomyocytes
 

Cytochrome c oxidase (CCO) is a copper-dependent enzyme of mitochondrial respiratory chain. In pressure overload-induced cardiac hypertrophy, copper level and CCO activity are both depressed, along with disturbance in mitochondrial fusion and fission dynamics. Copper repletion leads to recovery of CCO activity and normalized mitochondrial dynamics. The present study was undertaken to define the link between CCO activity and mitochondrial dynamic changes. Primary cultures of neonatal rat cardiomyocytes were treated with phenylephrine to induce cell hypertrophy. Hypertrophic cardiomyocytes were then treated with copper to reverse hypertrophy. In the hypertrophic cardiomyocytes, CCO activity was depressed and mitochondrial fusion was suppressed. Upon copper repletion, CCO activity was recovered and mitochondrial fusion was reestablished. Depression of CCO activity by siRNA targeting CCO assembly homolog 17 (COX17), a copper chaperone for CCO, led to fragmentation of mitochondria, which was not recoverable by copper supplementation. This study thus demonstrates that copper-dependent CCO is critical for mitochondrial fusion in the regression of cardiomyocyte hypertrophy.


 
There are a few studies already published that suggest NIR light being intimately related to Mitochondrial Fission and Fusion processes via impacts on Cytochrome c Oxidase, in one way or another...
 
More are to be expected...
 
There aren't a lot at this time in which the point is made in the abstract itself and I'm short on time at the moment to carefully select the non-abstract study passages confirming the fact of the importance of cytochrome c oxidase expression for mitochondrial fusion....
 
But I'd like to post about the importance of this fact, so I'm posting with just one study reference in support this evening...
 
:)

 

 

At some point soon, no regimen for managing mitochrondrial fission / fusion dynamics will be taken seriously that doesn't include a Near InfraRed Light exposure component...
-- Steve Buss, 2019-05-17
 

:)  :cool:  :)


Edited by HighDesertWizard, 18 May 2019 - 06:09 AM.

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#1383 Jschmoe

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Posted 18 May 2019 - 08:40 PM

 
 

From the study above we learn that different frequencies of Near InfraRed (NIR) light can either reduce or increase cytochrome c oxidase

  • Combined 750 and 950 nm NIR light exposure maximally inhibited cytochrome c oxidase expression
  • 810 nm NIR light exposure maximized cytochrome c oxidase expression

 

So, do we want to maximize it or minimize it?  It seems like it might depend...



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#1384 HighDesertWizard

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Posted 18 May 2019 - 08:52 PM

So, do we want to maximize it or minimize it?  It seems like it might depend...

 

I'm looking forward to hearing what Turnbuckle says about this...

 

That said, if I'm reading that and other studies correctly...

  • exposure to 750 nm and 950 nm light increases Mitochondrial Fission by inhibiting cytochrome c oxidase.
  • exposure to 810 to 860 nm light increases Mitochondrial Fusion by increasing cytochrome c oxidase

Graphic figure "B" makes clear why those values were selected. See my previous post for the caption.

 

 

rIZzOIoh.png

 

I bought a 940 nm flashlight this morning at Amazon. I'm hoping it will help with damage from an infection injury.injury.


Edited by HighDesertWizard, 18 May 2019 - 08:55 PM.

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#1385 lost69

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Posted 18 May 2019 - 09:09 PM

I'm looking forward to hearing what Turnbuckle says about this...

 

That said, if I'm reading that and other studies correctly...

  • exposure to 750 nm and 950 nm light increases Mitochondrial Fission by inhibiting cytochrome c oxidase.
  • exposure to 810 to 860 nm light increases Mitochondrial Fusion by increasing cytochrome c oxidase

Graphic figure "B" makes clear why those values were selected. See my previous post for the caption.

 

 

rIZzOIoh.png

 

I bought a 940 nm flashlight this morning at Amazon. I'm hoping it will help with damage from an infection injury.injury.

 

i used already a professional lamp but i had to discountinue C60.........the only downside i see is it cannot be mixed with C60

 

faceskin improved while using it (but platelet rich plasma mixed with dermapen makes so much more), i did not notice anything else.

i used it for subclinical hypothyroidism and it worsened while using lamp but once discontinued tsh got normal by the other protocols of stemcell renewal (i dont think the lamp had a delayed recovery effect)

 


Edited by lost69, 18 May 2019 - 09:13 PM.


#1386 Turnbuckle

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Posted 18 May 2019 - 09:23 PM

So, do we want to maximize it or minimize it?  It seems like it might depend...

 

On the plus side 5% doesn't seem that much, and in my own experiments with red light I subjectively get more than that. A number of areas are in reach of treatment. I posted this previously on my AD protocol thread--

 

...red light can be used to stimulate the function of tissues lying within an inch or so of the surface. It can be used to stimulate fat cells to give up their triglycerides, to stimulate testicles to produce more testosterone, to stimulate the thyroid gland and the vagus nerves, and by using it against the upper palate, the hippocampus. I've even found it effective against warts. IR and near IR aren't as good, in my opinion but they do penetrate more deeply. As for laser light, there is no reason to believe that it would be better, as coherent light becomes incoherent when passing through tissue.

 

 

For warts, removing the lens from a red diode flashlight and pressing the diode directly against the wart gives you a very high illuminance. One might also try it on various parts of the brain that lie close to the surface, such as Broca's and Wernicke's areas. For the hippocampus I haven't seen any results using it as I described above, likely because it is too deep, however there are products out there that go in through the nose. Here's one, though I have no idea if it works. One might enhance the effect of red light with N+R+stearic acid, which should boost ATP while keeping mitochondria in a fusion state.



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#1387 HighDesertWizard

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Posted 18 May 2019 - 10:55 PM

On the plus side 5% doesn't seem that much, and in my own experiments with red light I subjectively get more than that. A number of areas are in reach of treatment. I posted this previously on my AD protocol thread--
 
For warts, removing the lens from a red diode flashlight and pressing the diode directly against the wart gives you a very high illuminance. One might also try it on various parts of the brain that lie close to the surface, such as Broca's and Wernicke's areas. For the hippocampus I haven't seen any results using it as I described above, likely because it is too deep, however there are products out there that go in through the nose. Here's one, though I have no idea if it works. One might enhance the effect of red light with N+R+stearic acid, which should boost ATP while keeping mitochondria in a fusion state.

 
Turnbuckle...
 
I've become convinced that a habit of Red and Near Infrared (NIR) light exposure is among the most potent anti-aging techniques around, especially to NIR light. I came to believe NIR had to be tied to some fundamental biological process (like mito fission and fusion) after I came across these two studies (and others) I've summarized elsewhere at Longecity.

  • A link to my post about a study showing significant improvement in facial skin quality in 10 weeks.
  • A link to my post about an anecdotal case report showing a reversal of alzheimer's conditions in 4 weeks! I included a pic of the n = 1 wild-type human suffering from Alzheimer's with the nasal device you reference in her nose.

IMO, there's too much positive-for-health evidence already on the table about NIR especially to dismiss it. So then, after digesting the meaning of what the study and case report above reported--measurable results in 10 and 4 weeks, respecitvely--I'm on the hunt for the more general and fundamental biological processes are that underlie the reported effects.
 
The surprise was finding that study I've posted up thread. As far as I know, that's the only study reporting variable Cytochrome C Oxidase impacts--inhibited and increased expression--within the large Near Infrared Light range. It turns out, at least in that study, frequency of the light makes for a difference...
 
I expressed my hunch about what it means in my last post... (The bracketed italic text in the quotation below is editing of my previous statement for clarity.)
 

... if I'm reading that and other studies correctly...

  • exposure to 750 nm and 950 nm light increases Mitochondrial Fission by inhibiting cytochrome c oxidase [vis-a-vis the experiment control]
  • exposure to 810 to 860 nm light increases Mitochondrial Fusion by increasing cytochrome c oxidase [vis-a-vis the experiment control]

Edited by HighDesertWizard, 18 May 2019 - 11:07 PM.


#1388 Turnbuckle

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Posted 18 May 2019 - 11:12 PM

 
Turnbuckle...
 
I've become convinced that a habit of Red and Near Infrared (NIR) light exposure is among the most potent anti-aging techniques around, especially to NIR light. I came to believe NIR had to be tied to some fundamental biological process (like mito fission and fusion) after I came across these two studies (and others) I've summarized elsewhere at Longecity.

 

 

 

 

Of course increasing ATP will improve local cellular functioning. Especially in increasing testosterone levels and perhaps the stimulation of parts of the brain. But it is not a permanent, systemic improvement. It doesn't improve mito quality (by getting rid of defective mtDNA), and it does nothing for epigenetic aging. 


Edited by Turnbuckle, 18 May 2019 - 11:15 PM.


#1389 zorba990

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Posted 19 May 2019 - 04:05 PM

It would be good to know if fir sauna is pro fission or fusion so I can time that versus weight workouts and other fission methods. Seems pro fission

"Far-infrared radiation protects viability in a cell model of Spinocerebellar Ataxia by preventing polyQ protein accumulation and improving mitochondrial function"

https://www.ncbi.nlm...38/#!po=21.6667


"Expression of the mitochondrial fission protein Drp1 was individually found to be almost 1.8-fold and 4.2-fold increases in MJD 26 and MJD78 cells, compared with WT cells. Simultaneously, only MJD78 cells were accompanied with a significant reduction in the mitochondrial fusion proteins OPA1 and MFN2 (Fig. 4a). "

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#1390 HighDesertWizard

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Posted 19 May 2019 - 06:31 PM

It would be good to know if fir sauna is pro fission or fusion so I can time that versus weight workouts and other fission methods. Seems pro fission

"Far-infrared radiation protects viability in a cell model of Spinocerebellar Ataxia by preventing polyQ protein accumulation and improving mitochondrial function"

https://www.ncbi.nlm...38/#!po=21.6667


"Expression of the mitochondrial fission protein Drp1 was individually found to be almost 1.8-fold and 4.2-fold increases in MJD 26 and MJD78 cells, compared with WT cells. Simultaneously, only MJD78 cells were accompanied with a significant reduction in the mitochondrial fusion proteins OPA1 and MFN2 (Fig. 4a). "

 
zorba... Thanks for the study reference. I like the way you're thinking about this...
 
But also, there's an assumption those study authors make that is incorrect and you're following them in making it too... I was making the same mistake as late as 7 to 10 days ago...

:)

 

Our "labels" for Red-, Near Infrared- (NIR-), and Far Infrared- (FAR-) light, along with the frequency ranges associated with them, constitute a scheme for classifying light that will slow us down in understanding the reality of what these frequencies can accomplish within us as frequency-sensitive biological interventions.

 

Just like the thought and statement NIR light enhances fusion is mistaken, saying FAR light promotes fission is also mistaken...

 

That's the larger-insight gem implicit in the study I posted up thread...

 

--> 750, 810, and 950 are all NIR light frequencies, but they have significantly different impacts on cytochrome c oxidase expression, hence, the Electron Transport Chain, and, possibly, fission/fusion promotion.

 

... if I'm reading that and other studies correctly...

  • exposure to 750 nm and 950 nm light increases Mitochondrial Fission by inhibiting cytochrome c oxidase.
  • exposure to 810 to 860 nm light increases Mitochondrial Fusion by increasing cytochrome c oxidase
Graphic figure "B" makes clear why those values were selected. See my previous post for the caption.
 
rIZzOIoh.png

 

Please help me think through an N = 1 approach to get at the question fission/fusion impacts for different frequencies on myself...

  • I already have an 850 nm bulb.
  • I just purchased this 940 nm bulb at Amazon.
  • Key point... When irradiating body locations at close range, these are Spot Devices not Whole Body devices...
  • Differential effects can be evaluated at the same time by irradiating different body parts with different frequencies.

I'm new to the fission vs fusion impacts discussion.

 

What experiments do you suggest I do on 2 or more parts of my body to try to trigger differential effects of fission and fusion in a way that can be seen or felt?

 

A new N = 1 hack to try...

 

:)


Edited by HighDesertWizard, 19 May 2019 - 06:47 PM.


#1391 HighDesertWizard

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Posted 19 May 2019 - 08:06 PM

Our "labels" for Red-, Near Infrared- (NIR-), and Far Infrared- (FAR-) light, along with the frequency ranges associated with them, constitute a scheme for classifying light that will slow us down in understanding the reality of what these frequencies can accomplish within us as frequency-sensitive biological interventions.

 
... a stream of consciousness about this

  • so if those labels don't provide a good guide to effects on fission and fusion, what constructs do?
    • the optimal constructs ought to roughly to specific effects of specific biological objects
    • presumed fact from evidence... biological objects must exist that can differentiate, either individually or in concert with others, across and within the range of frequencies we speak in terms of, e.g., uvb, red, near infrared, violet, etc.
    • assumption... correct in general, but when wrong, hugely wrong... explosive evidence volume in the life sciences is normally distributed across the entire set of biological object types
    • so assemble the list of specific biological objects we already know light touches
    • the best biological construct guide for classifying light impacts will be on that list
  • .... reviewing the list .... please wait ....  :wacko:  :sad:  :mellow:  :cool:  ;)  :) 
     
  • ... what are the biological objects that should guide our classification scheme
     
  • ... my first guess
    • one or more specific Transient Potential Receptor (TRP) Channels

 

 

Evidence

 

2016, Photobiomodulation (blue and green light) encourages osteoblastic-differentiation of human adipose-derived stem cells: role of intracellular calcium and light-gated ion channels

 

Human adipose-derived stem cells (hASCs) have the potential to differentiate into several different cell types including osteoblasts. Photobiomodulation (PBM) or low level laser therapy (LLLT) using red or near-infrared wavelengths has been reported to have effects on both proliferation and osteogenic differentiation of stem cells. We examined the effects of delivering four different wavelengths (420 nm, 540 nm, 660 nm, 810 nm) at the same dose (3 J/cm2) five times (every two days) on hASCs cultured in osteogenic medium over three weeks. We measured expression of the following transcription factors by RT-PCR: RUNX2, osterix, and the osteoblast protein, osteocalcin. The 420 nm and 540 nm wavelengths were more effective in stimulating osteoblast differentiation compared to 660 nm and 810 nm. Intracellular calcium was higher after 420 nm and 540 nm, and could be inhibited by capsazepine and SKF96365, which also inhibited osteogenic differentiation. We hypothesize that activation of light-gated calcium ion channels by blue and green light could explain our results.

 

Study Result #2

 

The activation of 420 nm and 540 nm to promote osteogenic differentiation could be abrogated by TRPV1 and TRPC channel inhibitors

 

We performed Alizarin red (AR-S) staining as a mineralization assay in osteogenic medium with or without addition of TRP channel antagonists CPZ(5 μM) and SKF(5 μM) incubating for 10 minutes before photobiomodulation. There was a significant difference between OM and 420 nm, 540 nm, 810 nm groups. ***(P < 0.001) for 420 nm and 540 nm groups, and *(P < 0.05) for 810 nm group. There was no significant difference between the OM and 660 nm groups. Compared with 810 nm group, 420 nm (#P < 0.05) and 540 nm (###P < 0.001) had better effects in the ARS assay (Fig. 2A–C). The increase in the mineralization level in response to 420 nm and 540 nm groups was abrogated by the TRP channel antagonists CPZ and SKF (Fig. 2A–D). These results imply that TRP calcium channels play a role in blue and green light-enhancement of osteoblast differentiation. The AR staining after red light (660 nm) was partially abrogated by the TRP inhibitors. NIR light-mediated enhancement of osteogenic differentiation was not abrogated by TRP inhibitors, and therefore appears to occur via a different mechanism.

 

 

 

In the post quoted below I neglected to include a reference to the source url. The content is sourced here.

 

Transient Receptor Potential channels: Introduction

 

INTRODUCTION


The superfamily of transient receptor potential (TRP) ion channels consists of 28 distinct genes in mammals. They are grouped into six subfamilies by sequence homology: Canonical (TRPCs), Vanilloid (TRPVs), Melastatin (TRPMs), Mucolipins (TRPMLs), Polycystins (TRPPs), and Ankyrin repeat (TRPA). TRP channels may be generally described as cation permeable channels that function as cellular sensors responding to a broad range of stimuli.

Transient receptor potential (TRP) channels constitute a superfamily of cation permeable ion channels. They integrate multiple stimuli as cellular sensors, are widely expressed, and function in many physiological processes [1, 2]. While a subset of TRP channels primarily spans organellar membranes such as endolysosomes, most TRP channels promote Na+ and Ca2+ flux into cells [3]. In this article, we summarize molecular, structural, and functional properties of TRP ion channels.

 

DISCOVERY AND CLASSIFICATION


The founding member of the TRP channel superfamily was identified as essential component of Drosophila phototransduction [4]. A spontaneous mutation in the trp gene resulted in a transient receptor potential in response to continuous light. Drosophila TRP homologs have been identified in yeast, invertebrates and vertebrates. In mammals, 28 genes are classified as TRP channel subunits that are grouped into six subfamilies: the canonical TRPs (TRPCs), the vanilloid receptor TRPs (TRPVs), the melastatin TRPs (TRPMs), the mucolipins (TRPMLs), the polycystins (TRPPs), and the ankyrin transmembrane protein 1 (TRPA1) [1] (Figure 1). Unlike other ion channels that are classified according to a common ligand, function, or selectivity, TRP channel classification is currently based only on sequence homology [5, 6]. TRPCs, TRPVs, TRPMs, and TRPA1 have the highest homology to Drosophila TRP with TRPCs being the closest homologs. TRPMLs and TRPPs are more distantly related [7].

 

There's more at the link, but that's it for now...

 

Here's a classifying diagram shown at that link...

 

Note that "capsaicin receptor" is either a synonym for the TRPV1 channel or closely related to it...

 

fXPr2Wdh.png

 

Edited by HighDesertWizard, 19 May 2019 - 08:14 PM.


#1392 Turnbuckle

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Posted 19 May 2019 - 08:13 PM

Best to expand your infrared light investigations as there are other peaks in the visible. See--

 

The aim of the present work is to analyze available action spectra for various biological responses of HeLa cells irradiated with monochromatic light of 580–860 nm....Results: The peak positions are between 613.5 and 623.5 nm (in one spectrum, at 606 nm), in the red maximum. The far-red maximum has exact peak positions between 667.5 and 683.7 nm in different spectra. Two near infrared maxima have peak positions in the range 750.7–772.3 nm and 812.5–846.0 nm, respectively. Conclusions: In the wavelength range important for phototherapy (600–860 nm), there are four “active” regions, but peak positions are not exactly the same for all spectra. 
 

 

 

See also Mechanisms of Low Level Light Therapy.

What's available if you want specific wavelengths--Standard LEDs - Through Hole

 


Edited by Turnbuckle, 19 May 2019 - 08:25 PM.


#1393 zorba990

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Posted 20 May 2019 - 02:48 AM

I think that, in general, more work, heat, kinetic energy equals more fission. Rest, sleep, cold exposure during rest, would promote fusion. I'm thinking it's limiting considering only the effects of the frequency. A FIR sauna induces deep level heat which goes on to push body processes towards fission just at exercise with its heat, acid, and atp depletion does. Of course maybe after an adaptation period sauna no longer does this enough on its own and that's why detox with niacin and sauna became popular -- though ribose and niacinamide seems better and safer.

Edited by zorba990, 20 May 2019 - 02:50 AM.

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#1394 HighDesertWizard

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Posted 21 May 2019 - 04:08 AM

I think that, in general, more work, heat, kinetic energy equals more fission. Rest, sleep, cold exposure during rest, would promote fusion. I'm thinking it's limiting considering only the effects of the frequency. A FIR sauna induces deep level heat which goes on to push body processes towards fission just at exercise with its heat, acid, and atp depletion does. Of course maybe after an adaptation period sauna no longer does this enough on its own and that's why detox with niacin and sauna became popular -- though ribose and niacinamide seems better and safer.

 

We're free to believe what we like, of course, whether those beliefs fit demonstrated study facts, or not. But if we aren't willing to adapt / transform our beliefs to fit evidence, what's the point of spending time purporting to be informed, when we're not, on a site like Longecity?

 

Please stop promoting beliefs you hold that, per available evidence, are false and that you make no effort to back up with evidence. ! . ! . !

 

2019, Exercise training remodels human skeletal muscle mitochondrial fission and fusion machinery towards a pro-elongation phenotype

 

AIMS:

Mitochondria exist as a morphologically plastic network driven by cellular bioenergetic demand. Induction of fusion and fission machinery allows the organelle to regulate quality control and substrate flux. Physiological stressors promote fragmentation of the mitochondrial network, a process implicated in the onset of metabolic disease, including type 2 diabetes and obesity. It is well-known that exercise training improves skeletal muscle mitochondrial volume, number, and density. However, the effect of exercise training on muscle mitochondrial dynamics remains unclear.

METHODS:

Ten sedentary adults (65.8 ± 4.6 years; 34.3 ± 2.4 kg/m2 ) underwent 12 weeks of supervised aerobic exercise training (5 day/wk, 85% of HRMAX ). Body composition, cardio-metabolic testing, hyperinsulinaemic-euglycaemic clamps, and skeletal muscle biopsies were performed before and after training. MFN1, MFN2, OPA1, OMA1, FIS1, Parkin, PGC-1α, and HSC70 protein expression was assessed via Western blot.

RESULTS:

Exercise training led to improvements in insulin sensitivity, aerobic capacity, and fat oxidation (all P < 0.01), as well as reductions in body weight, BMI, fat mass and fasting glucose (all P < 0.001). When normalized for changes in mitochondrial content, exercise reduced skeletal muscle FIS1 and Parkin (P < 0.05), while having no significant effect on MFN1, MFN2, OPA1, and OMA1 expression. Exercise also improved the ratio of fusion to fission proteins (P < 0.05), which positively correlated with improvements in glucose disposal (r2  = 0.59, P < 0.05).

CONCLUSIONS:

Exercise training alters the expression of mitochondrial fusion and fission proteins, promoting a more fused, tubular network. These changes may contribute to the improvements in insulin sensitivity and substrate utilization that are observed after exercise training.

 

2019, Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training

 

AIM:

Healthy ageing interventions encompass regular exercise to prevent mitochondrial dysfunction, key player in sarcopenia pathogenesis. Mitochondrial biogenesis has been well documented, but mitochondrial remodelling in response to exercise training is poorly understood. Here we investigated fusion, fission and mitophagy before and after an exercise intervention in older adults.

METHODS:

Skeletal muscle biopsies were collected from 22 healthy sedentary men and women before and after 4 months of supervised training. Eight lifelong trained age- and gender-matched volunteers served as positive controls. Transmission electron microscopy was used to estimate mitochondrial content. Western blotting and qRT-PCR were used to detect changes in specific proteins and transcripts.

RESULTS:

After intervention, mitochondrial content increased to levels of controls. While enhancement of fusion was prevalent after intervention, inhibition of fission and increased mitophagy were dominant in controls. Similarly to PARKIN, BCL2L13 content was higher in controls. The observed molecular adaptations paralleled long-term effects of training on physical fitness, exercise efficiency and oxidative capacity.

CONCLUSIONS:

This study describes distinct patterns of molecular adaptations in human skeletal muscle under chronic exercise training. After 16 weeks of exercise, the pattern was dominated by fusion to increase mitochondrial content to the metabolic demands of exercise. In lifelong exercise, the pattern was dominated by mitophagy synchronized with increased fusion and decreased fission, indicating an increased mitochondrial turnover. In addition to these temporally distinct adaptive mechanisms, this study suggests for the first time a specific role of BCL2L13 in chronic exercise that requires constant maintenance of mitochondrial quality.


Edited by HighDesertWizard, 21 May 2019 - 04:20 AM.

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#1395 QuestforLife

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Posted 21 May 2019 - 11:51 AM

CONCLUSIONS:

This study describes distinct patterns of molecular adaptations in human skeletal muscle under chronic exercise training. After 16 weeks of exercise, the pattern was dominated by fusion to increase mitochondrial content to the metabolic demands of exercise. In lifelong exercise, the pattern was dominated by mitophagy synchronized with increased fusion and decreased fission, indicating an increased mitochondrial turnover. In addition to these temporally distinct adaptive mechanisms, this study suggests for the first time a specific role of BCL2L13 in chronic exercise that requires constant maintenance of mitochondrial quality.

 

No question exercise can maintain muscle, but elite athletes still get (and look!) old.  I wonder if we could improve the prognosis somewhat by increasing mitochondrial maintenance in other tissues. RED light may be ideal for treating the skin. 

 

I've been experimenting with a RED light face mask for a few weeks. I was originally sceptical but decided to try it based on the study you posted elsewhere HDW (https://www.ncbi.nlm...pubmed/24286286). Early signs are positive.  


Edited by QuestforLife, 21 May 2019 - 11:51 AM.

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#1396 HighDesertWizard

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Posted 21 May 2019 - 11:20 PM

Best to expand your infrared light investigations as there are other peaks in the visible. See--

The aim of the present work is to analyze available action spectra for various biological responses of HeLa cells irradiated with monochromatic light of 580–860 nm....Results: The peak positions are between 613.5 and 623.5 nm (in one spectrum, at 606 nm), in the red maximum. The far-red maximum has exact peak positions between 667.5 and 683.7 nm in different spectra. Two near infrared maxima have peak positions in the range 750.7–772.3 nm and 812.5–846.0 nm, respectively. Conclusions: In the wavelength range important for phototherapy (600–860 nm), there are four “active” regions, but peak positions are not exactly the same for all spectra.
https://sci-hub.se/1...pho.2005.23.355


See also Mechanisms of Low Level Light Therapy.

I noticed a few interesting things about that first paper...
  • as early as the year of its publication, 2005, it was known that different frequencies of Red Light have different effects
    • but I don't understand the biological dimensions referred to in Figure 2
  • this field has a new name, PhotoBioModulation (PBM), replacing many existing names for it in the literature
  • one of my posts above was an educated first guess about the topic of the the last sentence
    • seems to me that various types of Transient Receptor Potential (TRP) Channels are candidate "cytochrome c oxidase intermediaries"

GpfAuZBh.png


... a stream of consciousness about this

  • so if those labels don't provide a good guide to effects on fission and fusion, what constructs do?
    • the optimal constructs ought to roughly to specific effects of specific biological objects
    • presumed fact from evidence... biological objects must exist that can differentiate, either individually or in concert with others, across and within the range of frequencies we speak in terms of, e.g., uvb, red, near infrared, violet, etc.
    • assumption... correct in general, but when wrong, hugely wrong... explosive evidence volume in the life sciences is normally distributed across the entire set of biological object types
    • so assemble the list of specific biological objects we already know light touches
    • the best biological construct guide for classifying light impacts will be on that list
  • ... what are the biological objects that should guide our classification scheme
  • ... my first guess
    • one or more specific Transient Potential Receptor (TRP) Channels
 
Evidence

2016, Photobiomodulation (blue and green light) encourages osteoblastic-differentiation of human adipose-derived stem cells: role of intracellular calcium and light-gated ion channels

Human adipose-derived stem cells (hASCs) have the potential to differentiate into several different cell types including osteoblasts. Photobiomodulation (PBM) or low level laser therapy (LLLT) using red or near-infrared wavelengths has been reported to have effects on both proliferation and osteogenic differentiation of stem cells. We examined the effects of delivering four different wavelengths (420 nm, 540 nm, 660 nm, 810 nm) at the same dose (3 J/cm2) five times (every two days) on hASCs cultured in osteogenic medium over three weeks. We measured expression of the following transcription factors by RT-PCR: RUNX2, osterix, and the osteoblast protein, osteocalcin. The 420 nm and 540 nm wavelengths were more effective in stimulating osteoblast differentiation compared to 660 nm and 810 nm. Intracellular calcium was higher after 420 nm and 540 nm, and could be inhibited by capsazepine and SKF96365, which also inhibited osteogenic differentiation. We hypothesize that activation of light-gated calcium ion channels by blue and green light could explain our results.

Study Result #2

The activation of 420 nm and 540 nm to promote osteogenic differentiation could be abrogated by TRPV1 and TRPC channel inhibitors[/indent]

We performed Alizarin red (AR-S) staining as a mineralization assay in osteogenic medium with or without addition of TRP channel antagonists CPZ(5 μM) and SKF(5 μM) incubating for 10 minutes before photobiomodulation. There was a significant difference between OM and 420 nm, 540 nm, 810 nm groups. ***(P < 0.001) for 420 nm and 540 nm groups, and *(P < 0.05) for 810 nm group. There was no significant difference between the OM and 660 nm groups. Compared with 810 nm group, 420 nm (#P < 0.05) and 540 nm (###P < 0.001) had better effects in the ARS assay (Fig. 2A–C). The increase in the mineralization level in response to 420 nm and 540 nm groups was abrogated by the TRP channel antagonists CPZ and SKF (Fig. 2A–D). These results imply that TRP calcium channels play a role in blue and green light-enhancement of osteoblast differentiation. The AR staining after red light (660 nm) was partially abrogated by the TRP inhibitors. NIR light-mediated enhancement of osteogenic differentiation was not abrogated by TRP inhibitors, and therefore appears to occur via a different mechanism.

Edited by HighDesertWizard, 22 May 2019 - 12:06 AM.


#1397 Fafner55

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Posted 13 June 2019 - 11:25 AM

More support for the requirement of fission in mito quality control.

 

"DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass" (2019) https://www.nature.c...467-019-10226-9

Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochondrial fission is essential for muscle homeostasis is still unclear. Here we show that muscle-specific loss of the pro-fission dynamin related protein (DRP) 1 induces muscle wasting and weakness. Constitutive Drp1 ablation in muscles reduces growth and causes animal death while inducible deletion results in atrophy and degeneration. Drp1 deficient mitochondria are morphologically bigger and functionally abnormal. The dysfunctional mitochondria signals to the nucleus to induce the ubiquitin-proteasome system and an Unfolded Protein Response while the change of mitochondrial volume results in an increase of mitochondrial Ca2+ uptake and myofiber death. Our findings reveal that morphology of mitochondrial network is critical for several biological processes that control nuclear programs and Ca2+ handling.


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#1398 jgkyker

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Posted 13 June 2019 - 05:39 PM

From what I understand, based on some of the discussion here, fasting puts our body into a fission promotion state. (Let me know if I misunderstood.)

 

This has made me consider pushing all fission activities to night-time sleep, since the body is already in a fasting state, of sorts. Perhaps, this is why sleep is known to promote healing? Sleep could be, in effect as a whole, a major fission promoter.

 

What I would like to do is understand the half-lives of some of the fission promoting compounds we are taking, such as NR. For instance, if NR is completely out of my system after 8 hours, why not double this up with my daily sleep cycle. It seems like it could be or would be more effective, and when I awake to exercise or go about my day, I will not encounter the negative effects I have experienced with fission, such as exercise performance hits.



#1399 Turnbuckle

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Posted 13 June 2019 - 05:59 PM

From what I understand, based on some of the discussion here, fasting puts our body into a fission promotion state. (Let me know if I misunderstood.)

 

This has made me consider pushing all fission activities to night-time sleep, since the body is already in a fasting state, of sorts. Perhaps, this is why sleep is known to promote healing? Sleep could be, in effect as a whole, a major fission promoter.

 

What I would like to do is understand the half-lives of some of the fission promoting compounds we are taking, such as NR. For instance, if NR is completely out of my system after 8 hours, why not double this up with my daily sleep cycle. It seems like it could be or would be more effective, and when I awake to exercise or go about my day, I will not encounter the negative effects I have experienced with fission, such as exercise performance hits.

 

I don't recommend NR as it takes around 4 hours just to break it down to N+R, but 2 grams each of N+R can put you into a state of fission for days, as the NAD+/NADH ratio takes a while to fall. At least that has been my experience. Stearic acid will easily override that, if needed.


Edited by Turnbuckle, 13 June 2019 - 05:59 PM.

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#1400 Fafner55

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Posted 20 June 2019 - 12:53 PM

Reasons for the decline in mitochondrial fission and mitophagy with age are being uncovered.

  1. "PUM2 and MFF in the Dysregulation of Mitochondrial Fission in Aging" (2019) https://www.fightagi...ission-in-aging
  2. "The RNA-Binding Protein PUM2 Impairs Mitochondrial Dynamics and Mitophagy During Aging" (2019) https://www.ncbi.nlm...pubmed/30642763

 

 



#1401 Turnbuckle

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Posted 20 June 2019 - 07:26 PM

 

Reasons for the decline in mitochondrial fission and mitophagy with age are being uncovered.

  1. "PUM2 and MFF in the Dysregulation of Mitochondrial Fission in Aging" (2019) https://www.fightagi...ission-in-aging
  2. "The RNA-Binding Protein PUM2 Impairs Mitochondrial Dynamics and Mitophagy During Aging" (2019) https://www.ncbi.nlm...pubmed/30642763

 

 

 

The researchers illuminated some of the proteins that interact to reduce mito function, but those details are unnecessary for using N+R to eliminate dysfunctional mtDNA, which doesn't care how they got dysfunctional. And going after the protein that reduces clearance produced only marginal improvement to lifespans of their test animals (worms).


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#1402 Fafner55

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Posted 21 June 2019 - 01:17 AM

The researchers illuminated some of the proteins that interact to reduce mito function, but those details are unnecessary for using N+R to eliminate dysfunctional mtDNA, which doesn't care how they got dysfunctional. And going after the protein that reduces clearance produced only marginal improvement to lifespans of their test animals (worms).

 

Understanding how they got dysfunctional may lead to insight into how to best address the problem. The researchers found that PUM2 lead to dysregulation of mito fission, but over expression has been found to lead to premature aging, which suggests that PUM2 must be tightly regulated in healthy cells.. “PUMILIO hyperactivity drives premature aging of Norad-deficient mice” (2019) https://www.ncbi.nlm...icles/PMC640792

 

I have wondered how often I might need to invoke mitophagy. After multiple cycles of clearing a lifetime accumulation of dysfunctional mitochondria, what is needed for maintenance? Invoking mitophagy once every few years? Twice or three times per year? If mito fission becomes increasingly dysregulated with age (and not a simple linear accumulation of dysfunctional mitochondrial over time) then this is something that i will need to stay on top of on a regular basis to stay healthy.


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#1403 Turnbuckle

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Posted 21 June 2019 - 02:12 AM

They addressed the question of why mitochondria weren't be cleared as effectively with age, whereas there might be many reasons a problem occurred, such as the use of certain drugs, statins in particular. But the enhanced clearance with the protocols in this thread should take care of it no matter the source.



#1404 Fafner55

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Posted 21 June 2019 - 04:13 PM

The importance of maintaining a healthy population of mitochondria is highlighted by modeling of metabolic rate normalized for BMI and height. The high degree of correlation between predicted and actual survival curves in Figure 3 lend strong support for a mitochondrial decline theory of aging. While other factors that decline at similar rates and contribute to aging phenotypes, such as the accumulation of senescent cells and reduction in stem cell populations in some niches, there is little doubt that mitochondrial dysfunction if a major contributor to aging.

“Renormalized basal metabolic rate describes the human aging process and longevity” (2019) https://onlinelibrar...1111/acel.12968


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#1405 Graviton

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Posted 29 June 2019 - 02:17 AM

It was discussed before, but it is still inconclusive.

Fullerene particles concentrate inside mitochondria, and it works as a catalytic antioxidant. Is there any similar antioxidant working in the similar manner?

As far as we know, we have no information how these particles become an inactive form(s).

What would happen if fullerene ingestion rate surpass the clearance rate of fullerene inside mitochondria? Where would the excess of fullerene go?

Is there any possibility to cause any physical problem to intestinal organs such as spleen or liver that are associated with a build up of fullerene?


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#1406 Graviton

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Posted 01 July 2019 - 10:56 PM

Should be. Be aware that mito fusion can raise blood pressure in some people, and for me this raised it very rapidly.

What do you think mito-fusion can raise BP? Any scientific references?



#1407 Turnbuckle

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Posted 01 July 2019 - 11:47 PM

What do you think mito-fusion can raise BP? Any scientific references?

 

 

The literature speculates that mito fusion should lower BP, but I have had the opposite reaction. Fusion raises it and fission lowers it. I have seen this many times, and I'm not alone in this as one or two others on this thread have noted this as well. Why does it happen? I don't know. Does it happen with everyone? I can't say that either. Try it while monitoring your BP and let me know.



#1408 Graviton

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Posted 02 July 2019 - 01:31 AM

The literature speculates that mito fusion should lower BP, but I have had the opposite reaction. Fusion raises it and fission lowers it. I have seen this many times, and I'm not alone in this as one or two others on this thread have noted this as well. Why does it happen? I don't know. Does it happen with everyone? I can't say that either. Try it while monitoring your BP and let me know.

tried with about 5g of glycerol monostearate with soy lecithin in water. Not much reaction so far. By the way, why did you also say glycerol monostearate is more rapidly absorbed in the body than regular stearic acid? Similarly, it would be nice if you can link some scientific references.


Edited by Graviton, 02 July 2019 - 01:32 AM.


#1409 PAMPAGUY

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Posted 02 July 2019 - 09:27 AM

I have been gone for awhile.  Could someone please point me to the section where the latest protocol is listed.  Got everything ready to go.

 

Thanks 



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#1410 Turnbuckle

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Posted 02 July 2019 - 11:52 AM

A link to the latest protocol an always be found on my profile page.


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Also tagged with one or more of these keywords: nad, nad+, c60, mito, fission, fusion, stearic acid, mtdna, methylene blue

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