LONGECITY

It appears that ampk activation by salicylates inhibits fission if I read this right.
https://www.ncbi.nlm...pubmed/26196303

That might make magnesium or copper salicylate an attractive item for fission hangover.
Especially since it can be cardio protective.


"Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates endoplasmic reticulum stress-associated endothelial dysfunction.
Li J1, Wang Y2, Wang Y2, Wen X3, Ma XN3, Chen W2, Huang F2, Kou J2, Qi LW4, Liu B2, Liu K5.
Author information
Abstract
BACKGROUND AND PURPOSE:
This study aims to investigate whether and how pharmacological activation of AMP-activated protein kinase (AMPK) improves endothelial function by suppressing mitochondrial ROS-associated endoplasmic reticulum stress (ER stress) in the endothelium. Experimental approach Palmitate stimulation induced mitochondrial fission and ER stress-associated endothelial dysfunction. The effects of AMPK activators salicylate and AICA riboside (AICAR) on mitochondrial ROS production, Drp1 phosphorylation, mitochondrial fission, ER stress, thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome activation, inflammation, cell apoptosis and endothelium-dependent vasodilation were observed. Key results "Silencing" of TXNIP by RNA interference inhibited NLRP3 inflammasome activation in response to ER stress, indicating that TXNIP was a key link between ER stress and NLRP3 inflammasome activation. AMPK activators salicylate and AICAR prevented ROS-induced mitochondrial fission by enhancing dynamin-related protein 1 (Drp1) phosphorylation (Ser 637) and thereby attenuated IRE-1α and PERK phosphorylation, but their actions were blocked by knockdown of AMPK. Salicylate and AICAR reduced TXNIP induction and inhibited NLRP3 inflammasome activation by reducing NLRP3 and caspase-1 expression, leading to a reduction in IL-1β secretion. As a result, salicylate and AICAR inhibited inflammation and reduced cell apoptosis. Meanwhile, salicylate and AICAR enhanced eNOS phosphorylation and restored the loss of endothelium-dependent vasodilation in the rat aorta. Immunohistochemistry staining showed that AMPK activation inhibited ER stress and NLRP3 inflammasome activation in the vascular endothelium.
CONCLUSION AND IMPLICATIONS:
Pharmacological activation of AMPK regulated mitochondrial morphology and ameliorated endothelial dysfunction by suppression of mitochondrial ROS-associated ER stress and subsequent TXNIP/NLRP3 inflammasome activation. These findings suggested that regulation of Drp1 phosphorylation by AMPK activation contributed to suppression of ER stress and thus presented a potential therapeutic strategy for AMPK activation in the regulation of endothelium homeostasis.
Copyright © 2015 Elsevier Ltd. All rights reserved."

(I wonder where Acetyl L carnitine fits in....
Edit: it inhibits fission as well: https://www.ncbi.nlm...pubmed/20550520)

Aging Cell. 2010 Aug;9(4):570-9. doi: 10.1111/j.1474-9726.2010.00587.x. Epub 2010 Jun 9.
Acetyl-L-carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fission.
Palermo V1, Falcone C, Calvani M, Mazzoni C.
Author information
Abstract
In this work we report that carnitines, in particular acetyl-l-carnitine (ALC), are able to prolong the chronological aging of yeast cells during the stationary phase. Lifespan extension is significantly reduced in yca1 mutants as well in rho(0) strains, suggesting that the protective effects pass through the Yca1 caspase and mitochondrial functions. ALC can also prevent apoptosis in pro-apoptotic mutants, pointing to the importance of mitochondrial functions in regulating yeast apoptosis and aging. We also demonstrate that ALC attenuates mitochondrial fission in aged yeast cells, indicating a correlation between its protective effect and this process. Our findings suggest that ALC, used as therapeutic for stroke, myocardial infarction and neurodegenerative diseases, besides the well-known anti-oxidant effects, might exert protective effects also acting on mitochondrial morphology.
PMID: 20550520 DOI: 10.1111/j.1474-9726.2010.00587.x
Edited by zorba990, 16 June 2017 - 12:30 AM.

Well, I hoped if someone asked respectfully for help I thought it would be easy to help. I was wrong.

Out of the darkness there are only kinds of people to surface: the ones willing to help as they feel empathy for the others going down

and the ones feeling only they had to abide and in constant defence of their place.

Besides the ones that never saw it.

 

Anyway, I'm still grateful I got this information and Ill see if it can be helpful. Still hope you can enjoy the days left and

never get there.

Well, I hoped if someone asked respectfully for help I thought it would be easy to help.

 

From my research on mitochondria over the last few weeks I get that there is no one person in the world who has a good grasp on how this machinery works.Thus it is not easy at all.

 

Theorizing, testing on oneself is one thing, giving advice to others based on a vaque description is quite a different thing. Also most or all of us are not doctors. We are basicly in the same shoes. Just research, test and share, I'm sure people will give you some feedback when possible...

Judging by my own (see below) and experiences of others, N+R+exercise protocol has a strong impact on our bodies. Our reports point to weakness on the day of 'fission' and some of us report better overall condition during hours or days close after. I wonder what are the side effects (if any) and what is the long term outcome.

 

Some scientific articles point out that feeded state / overfeeding leads to fission.

Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure

 

'Cells exposed to a rich-nutrient environment tend to keep their mitochondria in a separated (fragmented) state, and mitochondria in cells under starvation tend to remain for a longer duration in the connected (elongated) state'

'… linking excess nutrient environment to progressive mitochondrial dysfunction, common to age-related diseases.'

 

 

For many of us it would mean we already have an access of divided mitochondria. So what would be the point to further increase fission with N+R+exercise protocol? It seems like not fission itself is the main goal of the protocol.

 

This article:

Frequency and Selectivity of Mitochondrial Fusion Are Key to Its Quality Maintenance Function

suggests that fission / fusion events take place between just a couple to as many as hundreds of events per mitochondrion per day and that optimal frequency has a great impact on quality control. Also fusion events, not only fission, seem to have a great impact on mitochondrial quality control. I wonder what our 'fission day' term really means.

 

These are some questions I'm struggling with and sharing here.

 

My recent experiences with N+R+exercise protocol:

 

Thu 8/6

Feeling fatique as usually at recent times.

 

8 am - black coffee, 20g dark chocolate, french croissant.

10.30 - black coffe, 1500 mg nicotinamide, 3g ribose orally

12-13pm Light exercise using 2.5kg and 6kg weights and some isometric exercises. Feeling strange, no desire to push.I wish it was warmer and I could sweat, as somehow I can't force myself to exercise hard enough to sweat. Short hot bath and cold shower. Not sure if a hot bath was a good idea, next time just a very short warm shower and as long as possible cold shower (exposure to cold enhances fission at least in BAT (Brown adipose tissue). Feeling refreshed, but dull and exhausted.

2pm - 2 slices of bacon, 1 egg, a slice of white bread. 5 dried plums

5-6pm a nap.

7pm beef + buckwheat

8pm 30g dark chocolate

9pm - light headache, sleepy, tired eyes

11pm bed

 

Fri 9/6

Woke up twice at night with light headache / hangover feeling.

Morning: light headache, sore muscles especially around neck (trapezius muscles).

After 1h dog walking feeling better, soreness almost gone.

Food.

dried plums, salad: 100g onion, 200g tomatos, 2 garlic cloves, spices, olive oil 30g. Mackerel in tomato sauce. 120g. Total ~ 600 kcal

1-2.30pm - a nap.

Supps: Cod liver oil..vit C 2g in 1 go, L-Lysine.

Cheese, prunes, nuts, chicken, wine.

30 min light exercise.

 

Sat 10/6

Starting 5 night shifts today, so it becomes difficult to judge my wellbeing.

Medium carb diet, raw onion, tomato, olive oil & garlic salads 3 times over the next days.

Nothing special to report.

Edited by hotbit, 16 June 2017 - 09:27 AM.

Judging by my own (see below) and experiences of others, N+R+exercise protocol has a strong impact on our bodies. Our reports point to weakness on the day of 'fission' and some of us report better overall condition during hours or days close after. I wonder what are the side effects (if any) and what is the long term outcome.

Some scientific articles point out that feeded state / overfeeding leads to fission.
Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure

'Cells exposed to a rich-nutrient environment tend to keep their mitochondria in a separated (fragmented) state, and mitochondria in cells under starvation tend to remain for a longer duration in the connected (elongated) state'
'… linking excess nutrient environment to progressive mitochondrial dysfunction, common to age-related diseases.'

For many of us it would mean we already have an access of divided mitochondria. So what would be the point to further increase fission with N+R+exercise protocol? It seems like not fission itself is the main goal of the protocol.

This article:
Frequency and Selectivity of Mitochondrial Fusion Are Key to Its Quality Maintenance Function
suggests that fission / fusion events take place between just a couple to as many as hundreds of events per mitochondrion per day and that optimal frequency has a great impact on quality control. Also fusion events, not only fission, seem to have a great impact on mitochondrial quality control. I wonder what our 'fission day' term really means.

These are some questions I'm struggling with and sharing here.

My recent experiences with N+R+exercise protocol:

Thu 8/6
Feeling fatique as usually at recent times.

8 am - black coffee, 20g dark chocolate, french croissant.
10.30 - black coffe, 1500 mg nicotinamide, 3g ribose orally
12-13pm Light exercise using 2.5kg and 6kg weights and some isometric exercises. Feeling strange, no desire to push.I wish it was warmer and I could sweat, as somehow I can't force myself to exercise hard enough to sweat. Short hot bath and cold shower. Not sure if a hot bath was a good idea, next time just a very short warm shower and as long as possible cold shower (exposure to cold enhances fission at least in BAT (Brown adipose tissue). Feeling refreshed, but dull and exhausted.
2pm - 2 slices of bacon, 1 egg, a slice of white bread. 5 dried plums
5-6pm a nap.
7pm beef + buckwheat
8pm 30g dark chocolate
9pm - light headache, sleepy, tired eyes
11pm bed

Fri 9/6
Woke up twice at night with light headache / hangover feeling.
Morning: light headache, sore muscles especially around neck (trapezius muscles).
After 1h dog walking feeling better, soreness almost gone.
Food.
dried plums, salad: 100g onion, 200g tomatos, 2 garlic cloves, spices, olive oil 30g. Mackerel in tomato sauce. 120g. Total ~ 600 kcal
1-2.30pm - a nap.
Supps: Cod liver oil..vit C 2g in 1 go, L-Lysine.
Cheese, prunes, nuts, chicken, wine.
30 min light exercise.

Sat 10/6
Starting 5 night shifts today, so it becomes difficult to judge my wellbeing.
Medium carb diet, raw onion, tomato, olive oil & garlic salads 3 times over the next days.
Nothing special to report.

Hi hobit,
Chocolate is rich in Stearic acid. Perhaps best to consume when attempting to induce fusion.

Sent from my SM-A520F using Tapatalk

 

Hi hobit,
Chocolate is rich in Stearic acid. Perhaps best to consume when attempting to induce fusion.

Sent from my SM-A520F using Tapatalk

 

 

Likely yes, I just forgot in the morning that I was going to try N+R later on.

P.S.
Quoting each time long posts makes the thread a bit too long and difficult to read / navigate.

Hi hobit,
Chocolate is rich in Stearic acid. Perhaps best to consume when attempting to induce fusion.

Sent from my SM-A520F using Tapatalk

Likely yes, I just forgot in the morning that I was going to try N+R later on.

P.S.
Quoting each time long posts makes the thread a bit too long and difficult to read / navigate.

Thanks for pointing that out. Will keep the quote short from now.

Two more supplements for the fission/mitophagy--fusion/biogenesis toolbox.

 

(1) Epicatechin enhances mito biogenesis. It is found in chocolate, but can be bought as an herbal supplement in acacia catechu extract, which is available with very high catechin content--40%, and was discussed here and on other threads at Longecity. I expect it to be even more effective in combination with PQQ.

 

(–)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle

 

Non-technical summary

 

During exercise, skeletal muscle performance depends in great part on the use of aerobic metabolism to supply the energetic demand of contractions. Endurance training increases the muscle aerobic capacity, which is not only associated with enhanced exercise performance, but also with a decreased risk of cardiovascular and metabolic diseases. Recently, it has been shown that regular use of small doses of dark chocolate may result in similar health benefits to exercise training. We show here that mice fed for 15 days with (–)-epicatechin (present in dark chocolate) had improved exercise performance accompanied by: (1) an increased number of capillaries in the hindlimb muscle; and (2) an increased amount of muscle mitochondria as well as signalling for mitochondrial biogenesis. These results suggest that (–)-epicatechin increases the capacity for muscle aerobic metabolism, thereby delaying the onset of fatigue. These findings may have potential application for clinical populations experiencing muscle fatigue.

 

https://www.ncbi.nlm...les/PMC3208228/

 

Components of oxidative phosphorylation complexes, mitofilin, porin, nNOS, p-nNOS, and Tfam [This is mitochondrial transcription factor A. Tfam is increased substantially even without exercise, see Fig. 6] as well as mitochondrial volume and cristae abundance were significantly higher with (–)-epicatechin treatment for hindlimb and cardiac muscles than exercise alone. 

 

 

 

 

(2) Tetramethylpyrazine (aka, ligustrazine) is a substance that appears to be synergistic with Tfam and thus useful for biogenesis--

 

Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by protecting TFAM from degradation.

 

Abstract

The natural small molecule compound: 2,3,5,6-tetramethylpyrazine (TMP), is a major component of the Chinese medicine Chuanxiong, which has wide clinical applications in dilating blood vessels, inhibiting platelet aggregation and treating thrombosis. Recent work suggests that TMP is also an antitumour agent. Despite its chemotherapeutic potential, the mechanism(s) underlying TMP action are unknown. Herein, we demonstrate that TMP binds to mitochondrial transcription factor A (TFAM) and blocks its degradation by the mitochondrial Lon protease. TFAM is a key regulator of mtDNA replication, transcription and transmission. Our previous work showed that when TFAM is not bound to DNA, it is rapidly degraded by the ATP-dependent Lon protease, which is essential for mitochondrial proteostasis. In cultured cells, TMP specifically blocks Lon-mediated degradation of TFAM, leading to TFAM accumulation and subsequent up-regulation of mtDNA content in cells with substantially low levels of mtDNA. In vitro protease assays show that TMP does not directly inhibit mitochondrial Lon, rather interacts with TFAM and blocks degradation. Pull-down assays show that biotinylated TMP interacts with TFAM. These findings suggest a novel mechanism whereby TMP stabilizes TFAM and confers resistance to Lon-mediated degradation, thereby promoting mtDNA up-regulation in cells with low mtDNA content.

 

https://www.ncbi.nlm...pubmed/28465355

  

 

 

Tetramethylpyrazine is hard to find as a retail product. It has been mentioned as a component of Chuan Xiong extract. 

Edited by Turnbuckle, 16 June 2017 - 11:39 AM.

Some scientific articles point out that feeded state / overfeeding leads to fission.

Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure

Quote

 

'Cells exposed to a rich-nutrient environment tend to keep their mitochondria in a separated (fragmented) state, and mitochondria in cells under starvation tend to remain for a longer duration in the connected (elongated) state'

'… linking excess nutrient environment to progressive mitochondrial dysfunction, common to age-related diseases.'

 

This has me scratching my head a bit. I have been including a 24 hour fast day as a part of my fission cycle. Is this in fact hindering mitophagy rather than helping it? Should my fasting be done the first day of fusion instead? It would seem, at the very least, that overfeeding should be avoided during fusion.

Edited by Richard McGee, 16 June 2017 - 06:23 PM.

 

Some scientific articles point out that feeded state / overfeeding leads to fission.

Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure

Quote

 

'Cells exposed to a rich-nutrient environment tend to keep their mitochondria in a separated (fragmented) state, and mitochondria in cells under starvation tend to remain for a longer duration in the connected (elongated) state'

'… linking excess nutrient environment to progressive mitochondrial dysfunction, common to age-related diseases.'

 

This has me scratching my head a bit. I have been including a 24 hour fast day as a part of my fission cycle. Is this in fact hindering mitophagy rather than helping it? Should my fasting be done the first day of fusion instead? It would seem, at the very least, that overfeeding should be avoided during fusion.

 

 

I expect that N+R driving up the NAD+/NADH ratio will override any natural tendency to fusion with fasting. And if one goal is to increase muscle mass, then stressing them with N+R fission + fasting + exercise with rapid high reps should be most efficient. Likewise, stearic acid and/or sulforaphane should override lesser drivers to fission.

 

   10 PM    Melatonin 20 mg -  initiate fusion at bedtime

 

20mg might be a huge dose according to MIT study.

0.3mg is enough for sleep purposes. For forced fusion higher dose might be good (?), but we should be careful not to overdose, as there are some side effects..

My melatonin (3mg tablets) just arrived today, preparing for a 'fission day' followed by a 'fusion day'.

 

I expect that N+R driving up the NAD+/NADH ratio will override any natural tendency to fusion with fasting. And if one goal is to increase muscle mass, then stressing them with N+R fission + fasting + exercise with rapid high reps should be most efficient. Likewise, stearic acid and/or sulforaphane should override lesser drivers to fission.

 

I like your reasoning. However, as there are so many variables influencing mito dynamics (circadian clock, type and amount of food / fasting, supplements taken, age / health condition) it will be interesting to test your hypothesis.

Edited by hotbit, 17 June 2017 - 02:27 PM.

 

 

I expect that N+R driving up the NAD+/NADH ratio will override any natural tendency to fusion with fasting. And if one goal is to increase muscle mass, then stressing them with N+R fission + fasting + exercise with rapid high reps should be most efficient. Likewise, stearic acid and/or sulforaphane should override lesser drivers to fission.

 

I like your reasoning. However, as there are so many variables influencing mito dynamics (circadian clock, type and amount of food / fasting, supplements taken, age / health condition) it will be interesting to test your hypothesis.

 

 

I wonder of these factors are cumulative or if these strong activators for fission/fusion will already set the limit?

 

If they don't, some supplements could enhance fission:

 

adrenal cortex (if it really does something...) (at least if diurnal rhythm is disturbed)

T4 or T3 (if hypothyroid or conversion is inhibited, also more likely useful in women)

(some of the) bio-activated B vitamins (as conversion is regulated hormonally, see above, ie B2.

Not sure what cofactors are needed in B3/Niacinamide conversion, but if methyl groups or FAD/FMN

play a role, this could make conversion more efficient/faster)

Taking them in the morning some time before exercising seems like a reasonable choice.

 

B5 in the early afternoon to enhance melatonin production in the evening.

 

Quite possibly this will have more impact if there's some kind of problem (with thyroid,

adrenals, nutrient-status, sleep etc.)

It appears that ampk activation by salicylates inhibits fission if I read this right.

https://www.ncbi.nlm...pubmed/26196303

 

AMP-activated kinase AMPK inhibits fission and stimulates mitogenesis.  ref

AMPK activators like AICAR (now banned) reputably were used to win the Tour de France.

You can increase the mitochondria and ATP output in muscles by taking an AMPK activator (such as Swanson Activ-AMP).

Endurance exercises can do the same thing. 

The resulting large increase in mitochondria mass is accompanied by an increase in fusion.

 

We may want to delay over-stimulating mitogenesis until after we have cleaned up the defective mitochondria with several fission/fusion cycles.

Edited by RWhigham, 17 June 2017 - 09:22 PM.

Two more supplements for the fission/mitophagy--fusion/biogenesis toolbox.

 

More mitogenesis/fusion stimulators:

     PQQ

     Epicatechin - cocoa

     Metformin

     Berberine

     Salicylates including white willow bark & Doan's Mg-salicylate   

     Jiaogulan extract  (Swanson's ActivAMP, reputably stronger than AICAR)

     AICAR  - the standard AMPK stimulator commonly used in laboratory experiments

Edited by RWhigham, 17 June 2017 - 09:23 PM.

Some of this is really starting to seem like a Scientology drug rundown/detox. Wonder if far infrared sauna would be a good addition for the heat stress.

Some of this is really starting to seem like a Scientology drug rundown/detox. Wonder if far infrared sauna would be a good addition for the heat stress.

 

Not wanna go too far OT, but what quickly came to mind was that one positive affect of sauna is to increase production of Tetrahydrobiopterin (BH4) by induction of a heat shock protein, which will stabilize GTP cyclohydrolase I (GTPCH), the enzyme which catalyzes the rate-limiting step in BH4 synthesis. Think I heard it from Dr. Martin Pall in one of his lectures.

see here:

https://www.research...e_NOONOO-_Cycle

and here ( as alleviated hypertension was mentioned in this thread)

https://www.research...isease_A_Review

Forgot this in a hurry: http://www.sciencedi...891584917300126

Pharmaceutical Approaches to Restore Mitochondrial function - behind paywall but Sci-hub has it.

 

Mitochondrial Biogenesis: Pharmaceutical Approaches  - free download at bottom of page

It appears some of you do fission in the morning and fusion in the evening of the same day. Others prefer to have them on different days. 

I am sure there is logic for both ways but I am still trying to understand it better.

 

Can I add Creatine to the fusion mix.

 

https://www.hindawi....l/2016/5152029/

 

I know from experience taking 3 grams stops virtually all muscle soreness after exercise for me. At my age my leg muscle don't like being pushed and will get very sore and stiff post work out and creatine makes a huge difference when I have used it.

20mg might be a huge dose according to MIT study.

 

I don't take melatonin for sleep purposes. I take it to regenerate my thymus gland.

It just happens that it also stimulates fusion.

Exogenous melatonin does not suppress endogenous production like most other hormones. Ref

 

Rejuvenation of degenerative thymus by oral melatonin

 

Melatonin rejuvenates degenerated thymus

 

The mice were drinking water that contained 15 mcg/mL of melatonin.

A mouse drinks about 5 mL/day, so they were drinking about 5x15 = 75 mcg/day of melatonin.

A typical adult mouse weighs 25 g. The human equivalent dose for a 80 kg person is:

75 mcg x 1/12 x  80,000/25 = 20,000 mcg = 20 mg    (the mouse-to-human HED factor is 1/12)

Edited by RWhigham, 18 June 2017 - 08:36 PM.

 

I don't take melatonin for sleep purposes. I take it to regenerate my thymus gland.

 

Exogenous melatonin does not suppress endogenous production like most other hormones. Ref

 

Rejuvenation of degenerative thymus by oral melatonin

 

Melatonin rejuvenates degenerated thymus

 

The mice were drinking water that contained 15 mcg/mL of melatonin.

A mouse drinks about 5 mL/day, so they were drinking about 5x15 = 75 mcg/day of melatonin.

A typical adult mouse weighs 25 g. The human equivalent dose for a 80 kg person is:

75 mcg x 1/12 x  80,000/25 = 20,000 mcg = 20 mg    (the mouse-to-human HED factor is 1/12)

 

 

 

RWhiggam, how long do you intend to supplement melatonin at this level? One of the studies mentions 60 days. Did you titrate up to this dose?

 

(Incidentally, I'm hoping you will start a separate thread on thymus regeneration - I'm very interested in the particulars of your regimen)

Edited by Richard McGee, 19 June 2017 - 03:05 AM.

RWhiggam, how long do you intend to supplement melatonin at this level? One of the studies mentions 60 days. Did you titrate up to this dose?

 

I started taking 9 mg of melatonin at bedtime sometime in 2015.

I Increased to 13 mg  May 1, 2017.

I increased to 20 mg  on June 4, 2017 (two weeks ago).

I expect to continue at 20 mg indefinitely.

 

As of now I have no idea how to gauge my thymus status.

See Josh Mitteldorf  "In preliminary experiments on himself, Greg Fahy has regrown thymus tissue with GH and DHEA."

 

Sorry for the detour. Let's keep this thread on mitochondrial rejuvenation  and "The Turnbuckle Procedure".

Edited by RWhigham, 19 June 2017 - 04:38 AM.

It's hard to find food grade stearic acid where I live.

The sources in the US are not expensive, but the shipping is very much so.

 

Will the salts of stearic acid work as well?

Can I add Creatine to the fusion mix.

 

https://www.hindawi....l/2016/5152029/

 

I know from experience taking 3 grams stops virtually all muscle soreness after exercise for me. At my age my leg muscle don't like being pushed and will get very sore and stiff post work out and creatine makes a huge difference when I have used it.

 

It might be the case. (Worth to properly read and confirm)

as:

 

Creatine Mimics the Effect of Drp1 on Synapse Density [....] Drp1 is believed to act specifically on mitochondrial fission

Source
 

also:

 

On Drp1 depletion (Figure 1A) almost 80% of cells had elongated (fused) mitochondria

Source

 

Thus it seems creatine could compliment N + R to boost fission. I will try.

Pharmaceutical Approaches to Restore Mitochondrial function - behind paywall but Sci-hub has it.

 

Mitochondrial Biogenesis: Pharmaceutical Approaches  - free download at bottom of page

Didn't find anything useful in these--a waste of time.

Edited by RWhigham, 20 June 2017 - 12:00 AM.

 

Can I add Creatine to the fusion mix.

 

https://www.hindawi....l/2016/5152029/

 

I know from experience taking 3 grams stops virtually all muscle soreness after exercise for me. At my age my leg muscle don't like being pushed and will get very sore and stiff post work out and creatine makes a huge difference when I have used it.

 

It might be the case. (Worth to properly read and confirm)

as:

 

Creatine Mimics the Effect of Drp1 on Synapse Density [....] Drp1 is believed to act specifically on mitochondrial fission

Source
 

also:

 

On Drp1 depletion (Figure 1A) almost 80% of cells had elongated (fused) mitochondria

Source

 

Thus it seems creatine could compliment N + R to boost fission. I will try.

 

 

I did miss that....I've assumed that Creatine was involved in fusion due to its abilities to remove very effectively the negative outcomes from exercise. I have tried Creatine over the weekend in a fission cycle and the cycle did seem shorter and not as intense but very positive effects. May be Creatine could be used to speed up the cycles and knock you around less.

I tried the Atomic Protocol, as described here and felt nearly nothing. Given the way this protocol has affected others, this lack of response lends support to that large doses of NR for 6 days invokes mitophagy. My 5 rounds of this protocol described here and ending here was very likely effective.

I tried the Atomic Protocol, as described here and felt nearly nothing. Given the way this protocol has affected others, this lack of response lends support to that large doses of NR for 6 days invokes mitophagy. My 5 rounds of this protocol described here and ending here was very likely effective.

 

 

I've noticed this too. Only the first try with the atomic protocol produced these dramatic effects, and subsequent tries seemed rather blah. This would be consistent with most of the mutated mitochondria being eliminated the first time. But mutations are only half the problem, and assuming the trial I did a couple of days ago continues to look good over the next week or so, I may have a protocol that addresses the rest of it. 

But mutations are only half the problem, and assuming the trial I did a couple of days ago continues to look good over the next week or so, I may have a protocol that addresses the rest of it. 

 

 

If mutations are only half the problem, what is the other half?