Great to get in touch with stem cell enthusiasts and would love to learn more about the subject from amazing LGcitizens.   

One question:

From what I read, injecting stem cells has sort of been norm in repairing ligament inguries. Regular treatment is to inject MSCs and HSCs into joints and wait till they differentiate. Do I get it right?

But to my astonishment, the other day a biology blogger told me the role of MSCs in ligament repairment is NOT to differentiate. Also, according to what he said, "In ligament repairment, MSCs are injected along with HA（hyaluronic acid），instead of HSCs...The real role of MSCs injected into joints is to inhibit inflammation and activate dormant stem cells already existed in joints to differentiate...". Shocking thing to know!!!!

Since I'm not a biology major and all my limited understandings of stem cells come from internet. It's beyond my ability to tell if the blogger is right or wrong. Any pro out there can help me with this?

The answer is meaningful to me 'cause I broke my shoulder joint and am supposed to have an arthroscopy. But my allergic asthma could pose a huge threat to my life under general anesthesia so I'm trying my best to avoid having any type of surgery. IF MSCs's role in ligament repairment, as the blogger said, is  to inhibit inflammation and activate dormant stem cells already existed in joints. I think I have other options to achieve the same goal.

Just want to know if the blogger is right or wrong in the workings of MSCs. No HSCs needed in ligament repairment? Hard to believe. Very different from what I read previously. BUT if he was right, it's goog news to me.

Many thanks in advance. 

Winnie

First I was kind of overwhelmed with the requirements, time and money needed for trying to replicate and/or incorporate the protocol in my own regimen. Then I started to feel it's actually a challenge .

I've therefore started to draft a regimen based on the TRIIM Protocol which I think I might be able to start in a month or so. Currently I'm collecting the necessary substances and tests needed. I've excluded HGH (Omnitrope) due to its lack of easy availability and will instead include some other substances which I think might be beneficial. From a testing point of view there will be no MRI's but some other tests with an emphasis on telomeres.

Because the the modified protocol is kind of ambitious I wonder if you see any obvious mistakes or easy improvements to it.

Below I've added is my first draft.

TRIIM Protocol without HGH and with some additional modifications

HGH has been left out because it seem to be a bit hard to obtain.

Pregnenolone has been included on a hunch.

Astragalus has been included since I'm currently using it (baseline/what I'm using today: once per day in the morning).

Gingko Biloba has been included since I'm currently using it (baseline: 1-3 times per week, usually around lunch).

Besides the substances below I consider the following to be included:

- Training sessions 2-3 times per week (baseline: currently 1 time per week)

- Regular saunas 4-5 times per week in order to decrease heavy metals (baseline: 1 time per half year)

- Transcendental Meditation at least 4-5 times per week around lunch (baseline: non-existent)

- Lower environmental stress (baseline: quite high)

- Low Carb High Fat diet (baseline: I'm currently in ketosis only one week every month or so)

1st week

Baseline tests

• Baseline blood tests: "Healthcheck XL+" with added Zinc, Cortisol, DHEAS, Thyroid tests. All tests during the morning.
• Baseline blood test: myDNAge Epigenetic Aging Clock test, around lunch
• Baseline blood test: RepeatDX 6-Panel assay Telomere length test, around lunch.
• Baseline blood test: LifeLength TAT, around lunch
• Baseline Saliva tests: Cortisol (morning), DHEA (morning)
• Baseline Heavy Metal Urine Test: 17 substances (Aluminum, Antimony, Arsenic, Lead, Cadmium, Chromium, Cobalt, Copper, Nickel, Palladium, Mercury, Iron, Platinum, Silver, Thallium, Zinc and Pewter), morning.
• uBiome Five Site bacterial tests: Gut, Mouth, Nose, Genitals, Skin)

Morning

1 x 25 mg DHEA

1 x 30 mg Pregnenolone

2 x 25 mg Zinc, organic

1 x 2500 IE Vitamin D3

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

Lunch

1x 105 mg Gingko Biloba

Evening

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

2nd week

Adjustment tests

Blood

• CRP, Hb, LPK, TPK, MCH, MCHC, MCV, EPK, EVF
• DHEAS
• HbA1c (glycated hemoglobin)
• Glucosis
• C-Peptide

Saliva

• Cortisol (morning), DHEA (morning)

Morning

1 x 25 mg DHEA

1 x 30 mg Pregnenolone

2 x 25 mg Zinc, organic

1 x 2500 IE Vitamin D3

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

Lunch

1x 105 mg Gingko Biloba

Evening

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

3rd week

Morning

2 x 25 mg DHEA (dose change to 50 mg if adjustment test results support this)

1 x 100 mg Pregnenolone (dose change to 100 mg if adjustment test results support this)

2 x 25 mg Zinc, organic

1 x 2500 IE Vitamin D3

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

Lunch

1 x 500 mg Glucophage (Metformin)

1x 105 mg Gingko Biloba

Evening

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

4th week

Adjustment tests

Blood

• CRP, Hb, LPK, TPK, MCH, MCHC, MCV, EPK, EVF
• DHEAS
• HbA1c (Glycated hemoglobin)
• Glucosis
• C-Peptide

Saliva

• Cortisol (morning), DHEA (morning)

Morning

2 x 25 mg DHEA (dose change if adjustment test results support this)

1 x 100 mg Pregnenolone (dose change if adjustment test results support this)

2 x 25 mg Zinc, organic

1 x 2500 IE Vitamin D3

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

Lunch

1 x 500 mg Glucophage (Metformin)

1x 105 mg Gingko Biloba

Evening

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

5th to 52nd week

Morning

1 x 25 mg DHEA

1 x 30 mg Pregnenolone

2 x 25 mg Zinc, organic

1 x 2500 IE Vitamin D3

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

Lunch

1 x 500 mg Glucophage (Metformin)

1 x 105 mg Gingko Biloba

Evening

1 x 250 mg Root Powder/225 mg Root Powdered Extract Astragalus

Week 53

Tests for results

• Blood tests: Healthcheck XL+ with added Zinc, Cortisol, DHEAS, Thyroid tests. All tests during the morning.
• Blood test: myDNAge Epigenetic Aging Clock test, around lunch.
• Blood tests: RepeatDX 6-Panel assay Telomere length test, around lunch.
• Blood test: LifeLength TAT, around lunch.
• Saliva tests: Cortisol (morning), DHEA (morning)
• Heavy Metal Urine Test: 17 substances  (Aluminum, Antimony, Arsenic, Lead, Cadmium, Chromium, Cobalt, Copper, Nickel, Palladium, Mercury, Iron, Platinum, Silver, Thallium, Zinc and Pewter), morning.
• uBiome Five Site bacterial tests: Gut, Mouth, Nose, Genitals, Skin

So, I have health problems. I have Autoimmune problems with Hashimoto's, Alopecia, Eczema. I also tested positive for Bartonella and Epstein Barr Virus recently (negative for Lyme though).

I'm a 31 year old male, and I have been sick for over 5 years, since early 2014. My main problems are fatigue, inability to handle stress, anxiety, and brain fog. Also, I tend to have a tired but wired feeling, and haven't been sleeping well lately.

I have tried a bunch of supplements, and take many now (I have listed the supplements I take at this google sites website: https://sites.google.com/view/hashimotosbartonellasupplement). I have used the website "selfdecode.com", to upload my 23andMe results, and get personalized recommendations based on my genetics. I came across a SelfDecode blog article that talked about brain histamine levels, related to the gene HMNT (specifically the SNP "rs1050891"), and the enzyme histamine-N-methyltransferase, which breaks down histamine in the brain. This is the article:  https://www.selfdecode.com/blog/article/brain-histamine-hnmt-13. 

My result for the SNP was homozygous "AA", which is the risk allele, and causes less breakdown of histamine by the enzyme, so can increase brain histamine. The blog article said that theanine and SAM-e can help with this. I already take theanine, and like its effects, although they are quite subtle at this point, as I've been taking theanine for about 9 months. But the article said that since SAM-e is a methyl donor and the enzyme HNMT inactivates histamine by methylating it, SAM-e may help HNMT work better to decrease brain histamine. 

So I ordered a bottle of SAM-e. I took one capsule of 200mg of SAM-e (from the brand Pure Encapsulations) yesterday and today. I can definitely feels the effects from it, seemingly about 30 minutes after taking it. The first night I took it, I felt pretty sleepy right after taking it, like a comfortable and relieving type of sleepy feeling. This feeling doesn't happen much anymore, and I welcome it. But I also felt a bit loopy and out of it from taking the SAM-e. The second day was similar. The second day I took the SAM-e in the afternoon (compared to the evening on the first day). I got comfortably relaxed after taking it, but then I went to work, which is DoorDash delivery currently. I noticed that while the SAM-e made me less anxious while waiting for the food in the restaurant, and I might have felt more comfortable talking to the other people waiting with me, I felt a little loopy, and like I had lost some where-with-all and alertness. I had lost some of that inner dialogue that makes me feel in control and alert, but can also contribute to feelings of anxiety. So I was in a bit of a daze. 

Usually I just feel really stressed, and like my brain is inflamed, so this relatively comfortable loopiness is still not completely hated by me, but I'm wondering why I feel like this, since many people report feeling more alert and have more energy from SAM-e. I know that SAM-e helps increase neurotransmitters like acetylcholine, dopamine, serotonin, norepinephrine and melatonin. So maybe it is activating serotonin or melatonin more for me?

Or maybe it is decreasing brain histamine, and the loopiness is a temporary side-effect?

I've also heard that SAM-e can cause mania in people who are bipolar. I'm not bipolar, but was wondering if there was any relation here, with my experience with SAM-e.

Anyway, I'm writing and asking this because I can't really tell if these effects from SAM-e are good or bad, worrisome or not. I may try it again tomorrow, I'm not sure. Or maybe next time I'll just take it right before I go to bed, and see how I feel in the morning.

So, I have health problems. I have Autoimmune problems with Hashimoto's, Alopecia, Eczema. I also tested positive for Bartonella and Epstein Barr Virus recently (negative for Lyme though).

I'm a 31 year old male, and I have been sick for over 5 years, since early 2014. My main problems are fatigue, inability to handle stress, anxiety, and brain fog. Also, I tend to have a tired but wired feeling, and haven't been sleeping well lately.

I have tried a bunch of supplements, and take many now (I have listed the supplements I take at this google sites website: https://sites.google.com/view/hashimotosbartonellasupplement). I have used the website "selfdecode.com", to upload my 23andMe results, and get personalized recommendations based on my genetics. I came across a SelfDecode blog article that talked about brain histamine levels, related to the gene HMNT (specifically the SNP "rs1050891"), and the enzyme histamine-N-methyltransferase, which breaks down histamine in the brain. This is the article:  https://www.selfdecode.com/blog/article/brain-histamine-hnmt-13. 

My result for the SNP was homozygous "AA", which is the risk allele, and causes less breakdown of histamine by the enzyme, so can increase brain histamine. The blog article said that theanine and SAM-e can help with this. I already take theanine, and like its effects, although they are quite subtle at this point, as I've been taking theanine for about 9 months. But the article said that since SAM-e is a methyl donor and the enzyme HNMT inactivates histamine by methylating it, SAM-e may help HNMT work better to decrease brain histamine. 

So I ordered a bottle of SAM-e. I took one capsule of 200mg of SAM-e (from the brand Pure Encapsulations) yesterday and today. I can definitely feels the effects from it, seemingly about 30 minutes after taking it. The first night I took it, I felt pretty sleepy right after taking it, like a comfortable and relieving type of sleepy feeling. This feeling doesn't happen much anymore, and I welcome it. But I also felt a bit loopy and out of it from taking the SAM-e. The second day was similar. The second day I took the SAM-e in the afternoon (compared to the evening on the first day). I got comfortably relaxed after taking it, but then I went to work, which is DoorDash delivery currently. I noticed that while the SAM-e made me less anxious while waiting for the food in the restaurant, and I might have felt more comfortable talking to the other people waiting with me, I felt a little loopy, and like I had lost some where-with-all and alertness. I had lost some of that inner dialogue that makes me feel in control and alert, but can also contribute to feelings of anxiety. So I was in a bit of a daze. 

Usually I just feel really stressed, and like my brain is inflamed, so this relatively comfortable loopiness is still not completely hated by me, but I'm wondering why I feel like this, since many people report feeling more alert and have more energy from SAM-e. I know that SAM-e helps increase neurotransmitters like acetylcholine, dopamine, serotonin, norepinephrine and melatonin. So maybe it is activating serotonin or melatonin more for me?

Or maybe it is decreasing brain histamine, and the loopiness is a temporary side-effect?

I've also heard that SAM-e can cause mania in people who are bipolar. I'm not bipolar, but was wondering if there was any relation here, with my experience with SAM-e.

Anyway, I'm writing and asking this because I can't really tell if these effects from SAM-e are good or bad, worrisome or not. I may try it again tomorrow, I'm not sure. Or maybe next time I'll just take it right before I go to bed, and see how I feel in the morning.

My research focuses on characterizing rare cell populations from bone marrow and peripheral blood with a specific emphasis on their progressive dysfunction in the aging process. Much of this work centers around hematopoietic stem cells (HSC). HSCs are residents of the bone marrow and give rise to all blood cells. The age-associated dysfunction of HSC and their progeny is a hallmark of an aging phenotype. The study of primary cells from the bone marrow presents several technical hurdles, ranging from techniques for cultivation outside of the body, to optimizing target cell harvesting, enrichment, and characterization. These challenges are compounded when we consider that there are subtle, yet often significant differences, in the behavior of blood cells between species. One of my favorite projects at Ichor involves optimizing the detection of rare engrafted donor cells in recipient mice, which is an important part of understanding the effects of transplanting donor cells to restore hematopoietic homeostasis in aged animals. There are many different models that can be used to track donor cells which only require a small quantity of peripheral blood for analysis. The donors in these models typically have a different phenotype from the recipient (e.g. GFP expression or unique surface antigens). This allows for donor and recipient cells to be distinguished in downstream analysis, enabling engraftment to be tracked over time. Flow cytometric analysis is a common (and my preferred) way to quantify the number of donor cells that are circulating in recipient blood. Not only can we track basic engraftment, but these cells can be further characterized post engraftment by looking at key surface markers, which can shed light on their function and activity after transplantation.

My research at Ichor is focused on engineering an antibody-like protein scaffold into targeted and highly specific therapies. What does that mean, exactly? The next time you’re watching TV and a drug commercial pops up, take a look at the name of the drug – if it ends with ‘-mab’, it’s what’s known as a monoclonal antibody (mAb). Since the first mAb therapy, muromonab, gained FDA approval in 1986, over 500 different mAbs have been approved or are being investigated for a myriad of diseases. Antibody treatments have very specific mechanisms of action, usually making them highly efficacious drugs with minimal side effects. They are often described with a ‘lock and key’ model – antibodies will bind tightly to their specific target once it is presented, with minimal off-target effects. Their biggest downside is cost – complex, full-length protein structures are costly to produce and are highly unstable. Antibodies are inherently fragile and contain tightly woven molecular structures which must be kept intact for full functionality. Prolonged storage, freezing and thawing, and temperature changes or exposure to room temperature will quickly and irreversibly denature antibodies, rendering them useless. This, combined with the complexity of production, makes antibody therapies expensive options for patients in developed countries, and often inaccessible to third-world and developing areas^[1][2]. In the US, for one year of treatment (excluding hospital fees), the average mAb is $96,731, and $142,833 for cancer mAb treatments, with many exceeding $200,000^[2]. Currently at Ichor, I’m developing a cost-effective protein scaffold which may be a suitable replacement for some antibody therapies. It has been shown to have antibody-like specificity for engineered target sequences, is incredibly heat and pH stable (Tm ~ 102C, pH stable 4-10), can be made orally-bioavailable and survive the GI tract, is easily expressed in E. Coli, and can be produced for a fraction of the cost of mAbs^[3]. Importantly, the exterior of our protein can be modified to recognize specific sequences without affecting its larger structure or stability – similar to mAbs. Our immediate goal is to prove efficacy against any therapeutically relevant targets, but we eventually hope to use RPtag’s uniquely stable properties in targeting novel anti-aging pathways which have been largely unreachable by mAbs, such as the GI tract.

We still have a long development road ahead of us, but we hope to one day be able to provide people with inexpensive and highly effective therapies for life-threatening diseases.

1. Elmore, S. NIH Public Access. 35, 495–516 (2007).

2. Hernandez, I. et al. THE AMERICAN JOURNAL OF MANAGED CARE ® Pricing of Monoclonal Antibody Therapies: Higher If Used for Cancer? 24, (2016).

3. Derosa, J. R. et al. RPtag as an Orally Bioavailable, Hyperstable Epitope Tag and Generalizable Protein Binding Scaffold. Biochemistry 57, 3036–3049 (2018).

My research at Ichor involves applying various biophysical methodologies towards small-molecule drug discovery. Numerous diseases originate from pathogenic protein-protein interactions (PPIs)^[1]. Disruption of these pathogenic PPIs with small molecules can be an effective therapeutic modality for disease^[1].

Effective characterization of a small molecule’s effect on a given PPI requires many experiments. Executing numerous experiments requires scalable quantities of biologically active protein. Researchers frequently produce human proteins in E.coli because E.coli can provide protein in large quantities, but this is not always the case. E. coli lack the machinery necessary to make certain human proteins properly, resulting in inactive product^[2]. This limitation forces researchers to settle with studying small pieces of the protein instead. These small pieces (commonly called fragments) can behave very differently than their native, full-sized counterparts, which can adversely impact research efforts when produced fragments are not physiologically relevant.

Ichor has developed a proprietary protein expression system which frequently allows for barriers commonly encountered in protein production to be overcome. Ichor’s ability to produce full-sized human proteins at scale using this technology enables extensive and otherwise inaccessible insights into certain PPIs. For the past several years the company has applied this technology in the study of various pathways associated with cancer and cellular senescence. My current work involves repurposing this platform for the study of other PPIs thought to be involved in the onset and progression of aging and age-associated diseases.

Citations:

[1] Scott, D.E., Bayly, A.R., Abell, C., and Skidmore, J. (2016). Small molecules, big targets: drug discovery faces the protein–protein interaction challenge. Nature Reviews Drug Discovery 15, 533–550.

[2] Rosano, G.L., and Ceccarelli, E.A. (2014). Recombinant protein expression in Escherichia coli: advances and challenges. Frontiers in Microbiology 5.

My previous work at Ichor examined the claims that administration of buckminsterfullerene in an olive oil solution leads to mammalian life extension. Buckminsterfullerene (also known as C60), is a molecule composed of 60 carbons which form a soccer ball like spherical structure. Carbon molecules link to each other in a matrix throughout the molecule, which give it interesting characteristics such as the ability to absorb free radicals and to appear as a red, wine-like color in solution. During our initial investigations, however, we became concerned with the quality of C60 that was being provided to people on the open market, specifically through online vendors. In a series of studies, I investigated the quality, health effects, and characteristics of C60 which being sold. The results of this research are being finalized and will be submitted for peer-review this year.

Beyond work with specific molecules like C60, Ichor is working to target each of the hallmarks of aging with specific interventions. The primary focus of my graduate work has been advancing Ichor’s flagship intervention for age-related macular degeneration (AMD). AMD is characterized by lysosomal dysregulation, driven by the accumulation of indigestible retinoid-based waste products that clutter the lysosome and inhibit native degradative processes. Our approach to this problem is an enzyme augmentation therapy (EAT) which introduces a recombinant enzyme that is capable of degrading the indigestible waste products in the lysosomes of affected cells. Our early proof-of-concept work on this program was published in late 2018 and demonstrated that this approach is efficacious in a mouse model of AMD. Since then, my emphasis has been on formulating the enzyme to produce a clinical candidate suitable for use in patients.

Then I found those Medizym.

Now at first glance, these seem to have the same components.  Even the dosages are the same.  But I wonder, is Rutoside trihydrate** (Rutin) Sophora japonica the same as Rutosid*** Sophora japonica?

Ok so anyway, what's up with the quantities being different.  The mg are the same, but the units are entirely different.  Can anyone convert these?  I searched online for how to convert them and found:

Protease HUT, USP, SAP   1 HUT = approx. 6.5 USP Amylase DU 1 DU = approx. 48 USP Lipase FIP, LU, FCCLU 

1FIP = approx. 2.5 LU/FCCLU No conversion available to USP

Source: https://www.enzymeessentials.com/shop/enzyme_labels.html

But this didn't help.

Before, I found this.

Flavenzym.

At first glance it looks the same as Wobenzym.  But then, wait a minute, what's that?  120mcg of Papain instead of 180mg?  Not a typo.

Does anyone know how to compare the amounts in the first two?

Lets say that you compare a person that drives a car with a person that sits in front of a computer. 

If a person drives a car for a couple of hours 5 times a month, how much does the chance of death increase?

Compared to a person that sits in front of the computer.

Thanks in advance.

Neurotherapeutics. 2018 Jan; 15(1): 156–175.

Published online 2018 Jan 16. doi: 10.1007/s13311-017-0593-0

PMCID: PMC5794704

PMID: 29340929

S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases Throughout Life

Jin Gao,1,2,3 Catherine M. Cahill,2 Xudong Huang,2 Joshua L. Roffman,1 Stefania Lamon-Fava,4 Maurizio Fava,1 David Mischoulon,1 and Jack T. Rogers2

Author information Copyright and License information Disclaimer

1Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA

2Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA

3Department of Clinical Psychology, Qilu Hospital of Shandong University, Qingdao, Shandong Province China

4Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA USA

Jack T. Rogers, Email: ude.dravrah.hgm@sregor.kcaj.

Corresponding author.

Go to:

Abstract

S-Adenosyl methionine (SAMe), as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties. Based on available evidence, this review focuses on the lifelong range of severe neuropsychiatric and neurodegenerative diseases and their associated neuropathologies, which have been linked to the deficiency/load of SAMe production or/and the disturbance in transmethylation pathways. Also included in this review are the present-day applications of SAMe in the treatment in these diseases in each age group.

Electronic supplementary material

The online version of this article (10.1007/s13311-017-0593-0) contains supplementary material, which is available to authorized users.

Keywords: S-Adenosyl-methionine, Transmethylation, Pathway, Psychiatric disease, Neurodegenerative disease

Excerpt (from full text, which is available for free):

The deficiency of SAMe may underlie the gradual hypomethylation of DNA that accompanies aging, and this hypomethylation can be alleviated by supplementation with SAMe [195]. The lower availability of SAMe may be related to the altered expression of genes involved in APP metabolism, finally producing the accumulation of Aβ peptide, contributing to the pathological processing of AD [6, 140]. DNA demethylation, when reduced by aging or nutritional deficiencies, may at least be partially avoided or restored by SAMe administration [6, 140]. In addition, BACE expression is modulated by methylation, and SAMe can restore its normal expression pattern [6]. Therefore, there have been several attempts to use SAMe nutritional supplementation in clinical trials in AD [7]. As an example of its mechanism of action, SAMe supplementation was shown to inhibit DNA demethylase, DNMT1 activity, and demethylation of PS1, a prime gene product involved in amyloidogenesis [143], as discovered in transgenic AD mice.

A further study examined whether SAMe could delay neuropathology in 3×Tg-AD mice, which harbor mutant genes for human AβPP, PS-1, and tau, here showing that SAMe supplementation in the diet did, in fact, reduce extracellular Aβ deposits [196]. SAMe treatment should therefore start early to effectively delay onset of AD symptoms. Fuso et al. [197] reported that SAMe reduced amyloid production and increased spatial memory in TgCRND8 mice. Here, SAMe inhibited the effects of B vitamin deficiency to induce PSEN1 and BACE1 expression and tau phosphorylation in TgCRND8 and wild-type mice. Certainly, SAMe treatment also reduced plaque spreading in pathways independent of B vitamin deficiency [197]. Persichilli et al. [198] reported a significant decrease of thiol levels when the B vitamin-deficient diet was supplemented with SAMe + superoxide dismutase and superoxide dismutase alone [198]. In a recent study on the APP transgenic mouse model of AD-like amyloid pathology, Do Carmo et al. [199] found that the early BACE-1 and global DNA demethylation were rescued by chronic administration of SAMe, which contributed to the reduction of amyloid pathology and the improvement in cognition function. In conclusion, these studies in AD support the rationale that it is possible to use SAMe to treat brain disorders with a plausible epigenetic mechanism. The studies are consistent with the hypothesis that SAMe administered orally is bioavailable in an active form or as an active metabolite in the brain.

I see this company advertising the product, but I can't find anecdotes of anybody taking it. Going by the name of rejuvant, and others, I believe.

It's quite expensive so I wouldn't want to try it without reading somebody elses' experience first.

I also find that a largely ketogenic diet helps to curb the appetite and thus control yourself from binge eating or eating junk

The diet needs to have a high level of vitamins, minerals (especially calcium), protein and fibre. The only thing I supplement on is Vitamin D3, K2 and Potassium

I will have

Natto (just the beans, not the mustard sauce it comes with). - Good for Vitamin K2, calcium and protein

Sardines - excellent source of calcium as well as protein and healthy fats like Omega 3

Aged cheese (such as Gouda) - great for calcium, K2 and protein

Egg - great for protein, vitamins and minerals

Dark chocolate (lindt now do a 95% variety!) - great for minerals like magnesium, iron and antioxidants - also great to have after sardines to remove aftertaste!

Nuts - great for protein, vitamins and minerals

Seaweed - great for minerals and calcium

Seeds - I like chia and hemp - great for protein

Greek yogurt/Kefir - great for protein and calcium

The grains I allow in my diet are black rice and oats in moderation. I'll also have a little bit of cereal called 'Allbran' which is packed with a lot of insoluble fibre

Love green/purple vegetables and berries for the fruit

Do others have other foods they have that are nutritionally dense? (flavour not an issue)

• Rhodiola 600mg
• Mucuna 800mg
• Flowering Quince 1g

Or is this overkill. I want it to be safe for people, but also effective. Many of these stacks don't have enough active ingredient to be effective.

So I'm trying to find the sweet spot of just the right amounts. Flowering Quince is the first one I'd cut back on if necessary.

Thoughts?

https://peterattiamd.com/davidsinclair2/

At 1:09 he talks about senescent cells and the very first thing that he comments on with regards to senescence is the fat cells. He says that the fat cells in an older mouse or human are excessively senescent; well not unknown information perhaps, we have heard the increased inclination of fat cells to senesce before. 

My question is, can we get rid of these fat cells simply by losing bodyfat? When we lose fat, do we remove the senascent cells as easily as the non-senescent fat cells? Or are the senescent ones somehow more resistant to diet and exercise.

All in all, do you think you'd contribute to your longevity by being ultra lean, say 5% bodyfat while retaining normally functioning hormones and a good amount of muscle mass, like this guy https://www.cbass.com/

I am wondering what is the most optimal time to take Metformin?, if you take it on an empty stomach and thirdly what dose and if so is it daily?

Many thanks!

S O U R C E :    Journal of Translational Medicine

ABSTRACT

Background

The effects of fasting on health in non-human models have been widely publicised for a long time and emerging evidence support the idea that these effects can be applicable to human practice.

Methods

In an open label longitudinal follow-up, a cohort of 78 adult men (aged 20 to 85 years) who fasted for 29 consecutive days from sunrise to sunset (16 h fasting—referred to as recurrent circadian fasting) in Pakistan, were studied. The primary outcomes of the fasting study was weight loss/recovery and the associated changes in blood pressure and circulating levels of surrogate markers linked to organ and system functions—including cardiovascular, metabolic and inflammation. Post-fasting outcomes include the regulation of physiological biomarkers.

Study design and meal variations. a Study design and b main variations in meal timing and intake. c Change in absolute weight (kg) in the study population during and after fasting. d Metabolic adaptation to fasting assessed by leptin, PPAR and fasting glucose levels

Results

Recurrent circadian fasting with weight loss reduced blood pressure (140.6 vs. 124.2 mmHg) and markers of cardiovascular risk (~ 4-fold for resistin; triglycerides: p < 0.0001). Reduced glycemia (p < 0.0001) and the associated changes in the regulation of ketosis (β-hydroxybutyrate) were accompanied by a metabolic shift (PPARβ, osteoprotegerin), suggesting the involvement of the different physiological systems tested. Elevated orexin-A levels (p = 0.0183) in participants indicate sleep disturbance and circadian adaptation. All participants had CRP level < 2 mg/l during the fasting period and a similar trend was observed for TNFα. While most SASP molecules were decreased after the fasting period, heightened levels of IL-8 and IL-6 suggest that some inflammatory markers may be elevated by recurrent circadian fasting. Importantly, older adults reveal similar or more substantial benefits from fasting.

Conclusions

Recurrent circadian fasting is beneficial at the cardiometabolic and inflammatory levels, especially for at-risk individuals—this is contingent on compliance towards the recommended dietary behaviour, which controls carbohydrate and caloric intake. These benefits from fasting may be particularly beneficial to older adults as they often exhibit abnormal cardiovascular, metabolic and inflammatory signatures.

F O R   T H E   C O R P U S   O F   T H E   S T U D Y ,   P L E A S E   V I S I T   T H E   S O U R C E .

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S O U R C E :    MedicalXpress

B E H I N D   P A Y W A L L   P R I M A L   S O U R C E :    JBMR

T I T L E :   Exercise degrades Bone in Caloric Restriction, despite Suppression of Marrow Adipose Tissue (MAT)

MRI Images of Mouse Femurs. Credit: University of North Carolina Health Care

A new study published today in the Journal of Bone and Mineral Research shows how bones in mammals are negatively impacted by calorie restriction, and particularly by the combination of exercise and calorie restriction. Maya Styner, MD, associate professor of medicine at the UNC School of Medicine, is the senior author on the study.

"These findings were somewhat of a surprise for us," Styner said. "Past studies in mice have shown us that exercise paired with a normal calorie diet, and even a high calorie diet, is good for bone health. Now we're learning this isn't true for exercise along with a calorie-restricted diet."

Styner's research focuses on the fat in bone marrow of mice. Although fat in the bone is poorly understood, to date it is thought to be harmful to bones of mammals, including humans, because it makes bone weaker. Less fat is usually an indication of better bone health. Styner's past studies have looked at the effects of calorie consumption on bone marrow fat, along with the role exercise plays. She's found that in obesity caused by excess calories, the amount of bone marrow fat is increased. Exercise in both obese and normal weight mice decreased bone marrow fat and improved the density of bones.

The latest study looked at what happens to bone marrow fat and overall bone health when restricting calories. There were four groups of mice in all—a group on a regular diet (RD), a group on a calorie-restricted (CR) diet, a RD group that exercised, and a CR group that exercised. Mice in the CR group ate 30 percent less than what RD mice ate.

For context in humans, according to the United States Department of Agriculture (USDA), a 'moderately active' woman around the age of 30 should consume 2,000 calories per day. A 30 percent reduction would equal a diet of 1,400 calories per day, which is around the amount suggested to most women trying to lose weight at a rate of one pound a week.

Styner found that mice in the CR group lost weight, but also had an increase in bone marrow fat.

"This was mild caloric restriction, and we found a significant increase of fat in the bone marrow," Styner said. "This group also had a decrease in bone quantity—they had less bone overall due to the cut in calories."

Both CR groups of mice were given supplements of vitamins and minerals to match the amount the RD group received from the extra food they ate. This, Styner says, is an indication that the effect on bone health was from calorie restriction, and not a lack of nutrients.

When exercise was introduced to the CR group, bone marrow fat decreased as it had in previous studies, but the overall quantity and quality of bone decreased as well. Instead of making bones more robust, exercise made bones more fragile when paired with calorie restriction.

"Looking at this from a human perspective, even a lower calorie diet that is very nutritionally sound can have negative effects on bone health, especially paired with exercise," said Styner. "This is important for women to consider because as we age our bone health starts to naturally decline. Your calorie intake and exercise routine can have a great impact on the strength of your bones and your risk for break or fracture."

Styner says her team is now planning to conduct more research to understand the purpose of bone marrow fat and why it is affected by diet and exercise. This study was funded by grants from the National Institutes of Health (NIH) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

.

.

S O U R C E :    MedicalXpress

B E H I N D   P A Y W A L L   P R I M A L   S O U R C E :    JBMR

T I T L E :   Exercise degrades Bone in Caloric Restriction, despite Suppression of Marrow Adipose Tissue (MAT)

MRI Images of Mouse Femurs. Credit: University of North Carolina Health Care

A new study published today in the Journal of Bone and Mineral Research shows how bones in mammals are negatively impacted by calorie restriction, and particularly by the combination of exercise and calorie restriction. Maya Styner, MD, associate professor of medicine at the UNC School of Medicine, is the senior author on the study.

"These findings were somewhat of a surprise for us," Styner said. "Past studies in mice have shown us that exercise paired with a normal calorie diet, and even a high calorie diet, is good for bone health. Now we're learning this isn't true for exercise along with a calorie-restricted diet."

Styner's research focuses on the fat in bone marrow of mice. Although fat in the bone is poorly understood, to date it is thought to be harmful to bones of mammals, including humans, because it makes bone weaker. Less fat is usually an indication of better bone health. Styner's past studies have looked at the effects of calorie consumption on bone marrow fat, along with the role exercise plays. She's found that in obesity caused by excess calories, the amount of bone marrow fat is increased. Exercise in both obese and normal weight mice decreased bone marrow fat and improved the density of bones.

The latest study looked at what happens to bone marrow fat and overall bone health when restricting calories. There were four groups of mice in all—a group on a regular diet (RD), a group on a calorie-restricted (CR) diet, a RD group that exercised, and a CR group that exercised. Mice in the CR group ate 30 percent less than what RD mice ate.

For context in humans, according to the United States Department of Agriculture (USDA), a 'moderately active' woman around the age of 30 should consume 2,000 calories per day. A 30 percent reduction would equal a diet of 1,400 calories per day, which is around the amount suggested to most women trying to lose weight at a rate of one pound a week.

Styner found that mice in the CR group lost weight, but also had an increase in bone marrow fat.

"This was mild caloric restriction, and we found a significant increase of fat in the bone marrow," Styner said. "This group also had a decrease in bone quantity—they had less bone overall due to the cut in calories."

Both CR groups of mice were given supplements of vitamins and minerals to match the amount the RD group received from the extra food they ate. This, Styner says, is an indication that the effect on bone health was from calorie restriction, and not a lack of nutrients.

When exercise was introduced to the CR group, bone marrow fat decreased as it had in previous studies, but the overall quantity and quality of bone decreased as well. Instead of making bones more robust, exercise made bones more fragile when paired with calorie restriction.

"Looking at this from a human perspective, even a lower calorie diet that is very nutritionally sound can have negative effects on bone health, especially paired with exercise," said Styner. "This is important for women to consider because as we age our bone health starts to naturally decline. Your calorie intake and exercise routine can have a great impact on the strength of your bones and your risk for break or fracture."

Styner says her team is now planning to conduct more research to understand the purpose of bone marrow fat and why it is affected by diet and exercise. This study was funded by grants from the National Institutes of Health (NIH) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

.

Because of this fab video... https://www.youtube.com/watch?v=CSNnIg2cVjc&feature=youtu.be ...I am interested in learning how to electrically ground myself much more of the time.

Can anyone provide guidance for specifically how to...

1. Measure the groundedness of surfaces in my home (floors, bed).
2. Ground the places I spend a lot of time (desk, kitchen, bed).
3. Measure the conductivity of materials (socks, shoes, carpets and other flooring).

Thank you

It is apparent to me that we are doing things all wrong if we truly want to believe and manifest the ability to live for hundreds of years. Perhaps we believe the science we see in the anti-aging research, but we do very little to support that belief. When we're not researching or discussing this topic specifically, our minds are usually falling back into old beliefs.  Getting past this may help us to make larger and faster breakthroughs than ever thought possible (by most).

I propose a very simple experiment. It will be necessary for many people to join in for us to see results.  It is a very simple thing that I propose we all do.

Are you ready for the life-changing, reality-altering, mind-blowing, incredibly arduous (not), chore that will change many of our lives for the better? All you have to do is....

..... add 200 years to the age of any adult who's age you are estimating. 

The next time you meet a person who you think looks 5-20 years younger than they are, catch yourself and analyze that thought. More importantly don't say "You look great for your age." Instead, just say "Wow, you look great." If that person has even one wrinkle or gray hair, think to yourself, "They could look so much healthier". Making a big deal about a few years of what appears to be static aging of the skin, is setting our beliefs where we don't want them to be IF we want to look and feel vibrant, youthful and healthy after reaching the age of 100, 150, etc.

Considering something before you can accept that it's possible is very important. This technique is used in brainwashing. Brainwashing others may be a bad thing, but if we are using it on ourselves for good, I think it can only be helpful (please share if you know otherwise). Our brains are computers that translate the world to us. They communicate with is and vice versa in a code that we get to modify. If you want to change reality, don't let others write your code for you. When you start this experiment, it will seem forced at first. More and more evidence of youthing or very delayed aging will come your way to support your consideration/belief. Don't question it or think it's miraculous, just think "This isn't particularly amazing science. It's obvious aging is optional." You can look into it and be excited, but watch your thoughts, keep track of where they go and notice how many thoughts are tied into our beliefs about aging and disease.

In order to be truly into this experiment and not have trouble communicating with those who aren't playing the game, you can just avoid stating ages to others who won't understand. If someone pins you down to give an age estimate, instead of saying "She must have been about 25." You can say "She looked old enough to have graduated college in recent years." intead of "he looked about 55" try "It would be impossible to guess his age, but he had a few gray hairs and maybe some wrinkles.". 

If we want to be healthy at 200, we must believe that the person we just ran into who looks like they just finished puberty could be 100 years old.

Who's in?

I know that you have Selank, N-Acetyl Selank, and N-Acetyl Selank Amidate.  I understand that the NA Selank *should* be more bio-available though almost all of the research is Russian and on the non-acetylated version.  I'm unsure what the proposed advantage is of NA Selank Amidate is but I'm guessing it is thought to be more bio-available still?

I'm wondering if anyone has any personal experience or knowledge in this area that they could share?

Thanks,

I tried tianeptine, I never got any tolerance and it does work to brighten my mood at a very low dose (~10mg / day or even under). I don't use it every day, and if I don't there are no issues.

I tried once Hydrocodone for actual pain, and it had 0 effect on the pain, and no euphoria or nothing.

Recently I tried poppy tea, with no effect whatsoever from 100gr. The brand is well known among users.

I am confused as to which receptor is responding and which is not, cause these should share the mode of action.

Or should I just get the powder?

Zinc, Iron, phosphorus, vitamin D, vitamin C?

I can't seem to remember the drug's name nor can I find his post.

Does anyone know the name of the drug?

Then came the lawyers and Zicam was was blamed for casuing people to lose their sense of smell. It was total BS. The nasal zinc formula worked too good and it actually got rid of colds like it said on the boxes. The lawyers got it removed from the shelves.

The stuff you buy today is total snae oil. It does not work because there is no zinc in it.

Ever since it has been removed, each and every year, my wife and I have resumed getting colds a couple of times a year just like we did before Zicam first came out.

The active ingredient that killed the rhinovirus was the zinc gluconate, which anyone can buy in bulk. The problem is that I can't find out how to dissolve it and make my own "goop" for nasal passages. It remains a "hard" powder that is abbrasive to use.

Can anyone tell me how to dissolve it?

It is also known that some supplements are known to reduce or remove scar tissue especially if applied locally. Fasting is also said to help remove scar tissue in the skin.

What are those supplements known to remove scar tissue?

However, in the long term, glial scars also block the growth of new neurons, and thus prevent the brain from fully healing.

In the past, attempts to remove glial scars so that neurons can regenerate have not been very successful. 

But Professor Gong Chen and his team at Pennsylvania State University have been trying a new approach, which is based on using a set of drugs to reprogram the glial cells within the scar so that they turn into neurons. 

The discovered that a cocktail of 4 drugs (namely CHIR99021, DAPT, LDN193189 and SB431542) can efficiently turn human astrocytes (the main glial cell in the brain) into functioning neurons. 

So rather than trying to dissolve or remove the glia scar, as previous approaches have tried, Prof Chen is actually converting the scar into new neurons.

Article here: Simple drug formula regenerates brain cells

Published study: Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming

After a viral brain infection I had in 2005, I experienced some brain damage, with some of my mental faculties being instantly and permanently damaged or degraded. After this brain infection I also went on to get myalgic encephalomyelitis (chronic fatigue syndrome).  

So I am very interested in approaches that can repair brain damage.

But if I were to eat 1500 calories a day and on average burn 2500 calories a day, at some point I would have run out of reserve to burn and at that point wouldn't it be better to match match my intake and expenditure instead of further restrictions

I can see it work as part of a healthy diet, but I cant see it work as a complete lifestyle - unless I am missing something about it. Does my BMR reduce to compensate (slower metabolism, longer life?) This in turn would mean that should I resume eating 'normally' again, the weight gain would be much easier.

I'm sure there would have been experiments done (on mice or other animals) with this - a whole life of eating less calories than you expend. Would like to check it out

I have been arranging group buys for chemicals and been distributing NSI-189 and other nootropics to Longecity members for about five years now, I have asked a price for a bulk purchase of 5 grams from a reputable source and I got a price of 250mg/$70 that could get over $600 if someone would buy 5mg vials in retail. BPC-157 is orally bioavailable and can also be used sublingually.

Anyone that has any chronic issue with any of the above might want to consider it for.

-Ligaments, muscle and bone injuries

- Ulcers, leaky gut, Crohn’s disease

-Skin burns

-Increase in neuronal plasticity

-Analgesic qualities.

Anyone that might be interested, please post in the thread below.

https://www.longecity.org/forum/topic/106375-bpc-157-group-buy/