LaraPo
#557
Merz Pharma (Merz Aesthetics) claims that their injectable implant Radiesse stimulates collagen and elastin production through its unique composition and mechanism of action. Radiesse contains microspheres of CaHA, a biocompatible substance also found in bones. Over time, the CaHA particles act as a scaffold, stimulating fibroblasts (skin cells) to produce collagen and elastin. The collagen production can last up to a year, while elastin stimulation typically lasts for several months.
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Interestingly if you ask chatGPT to answer the question not broken down into steps it does not get the correct answer. (or perhaps moreso misses out a key component)
You said:
to what extent is elastin production dependent on the mitochondrial membrane potential
ChatGPT said:
Great question! The relationship between elastin production and mitochondrial membrane potential (ΔΨm) is indirect but important, especially in the context of cellular metabolism, oxidative stress, and overall cell health.
1. Basic Connection Between Mitochondria and Protein Synthesis (like Elastin)
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Mitochondrial membrane potential (ΔΨm) is essential for ATP production via oxidative phosphorylation.
- ATP is required for protein synthesis, including elastin, which is a major extracellular matrix (ECM) protein important for tissue elasticity (e.g., skin, lungs, vasculature).
- If ΔΨm is disrupted, ATP levels drop, leading to impaired general protein synthesis, including elastin.
2. Mitochondrial ROS and ECM Regulation
- Mitochondrial dysfunction and ΔΨm depolarization often increase reactive oxygen species (ROS).
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High ROS levels can damage signaling pathways and proteins directly or indirectly regulate elastin gene (ELN) expression.
- Oxidative stress can downregulate elastin synthesis and promote ECM degradation (via MMPs—matrix metalloproteinases).
3. Mitochondrial-Dependent Signaling Pathways
- Mitochondrial health (reflected in ΔΨm) affects TGF-β, Notch, and other pathways that modulate elastin gene expression.
- For example, TGF-β signaling, crucial in elastogenesis, is sensitive to mitochondrial ROS and ATP levels.
4. Cell Types and Context Dependence
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Fibroblasts, vascular smooth muscle cells, and other elastin-producing cells rely on mitochondrial function.
- In diseases like COPD, vascular diseases, and aging, impaired mitochondria (low ΔΨm) correlate with reduced elastin content and increased tissue stiffness.
Summary:
Elastin production is dependent on mitochondrial membrane potential indirectly, via:
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ATP production needed for synthesis.
- Regulation of ROS that can damage elastin or suppress its gene expression.
- Impact on signaling pathways that govern ECM remodeling and elastin synthesis.
When ΔΨm is compromised, elastin synthesis is typically reduced, and ECM degradation is enhanced — contributing to diseases involving tissue elasticity loss.
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I’m not terribly concerned about the skin aspect. That is not where the lack of elastin is going to kill you.
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LaraPo
#560
That implant is not about skin only, it’s distributed in all tissues and adds so needed collagen and elastin. Skin, our biggest organ, is very important for general health but often is undervalued.
Last week I had a very unique experience with meeting a woman who’s 102 years old. It was the first time in my life that I interacted with such an old person in real life. What amazed me was her skin. It didn’t have any blemishes, growths, rough spots, etc. it was all even and clean, with almost no wrinkles. She did have dementia, but besides that, she didn’t have major health issues. Good skin is a sign of good health and good genes imo.
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Do they specifically die because they lack elastin or are other factors at play here?
Without enough functional elastin, lungs fail, the heart fails, arteries fail.
One can have perfect markers, triglycerides perfect, heart rate perfect, strength perfect but that is not enough without perfect elastin.
https://journals.physiology.org/doi/full/10.1152/japplphysiol.90563.2008
Other functional aspects become irreversibly impaired as well. This is easy to see in aging people who are athletic. Their stride changes as elastin is lost, their range of motion is reduced due to loss of flexibility, tendons and ligaments require elastin for flexibility and the essential rebound it provides. As people age they don’t “bounce” like younger people with more elastin. This is the visible and irreversible effect of loss of elastin.
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Dr.Bart
#563
If you understand the elastin problem, then you will know the maximum human life span is 120 regardless of living in a bubble.
OK, so now we are up to 140 years old as potential maximum human life span, that’s progress !
I think a person with good genetics, lifestyle from birth that can slow down aging to 0.5 (so immaculate diet, exercise, sleep, stress reduction, excellent dental care, social support), living in a relatively isolated community so they could avoid CMV/EBV/HPV and other DNA based viruses, worst forms of influenzae, coronavirus and other infectious agents, avoid excessive Sun and other environmental toxic hazards and lots of luck - could live to 140 years old.
And that’s without pharmaceuticals, supplements and worked out Yamanaka factor therapy.
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Neo
#564
Do you know how important it is for the CNS/brain?
JuanDaw
#565
From Nick Norwitz.
The Key To SLOWING Aging? $1 Omega-3 vs. $2M Anti-Aging Protocol
6:45 - Omega 3 (1 g/day) improved scores on Phenoage, Grimage2, and DunedinPace
7:20 - Omega 3 alone at 1g/da was lowering the DunedinPACE estimated rate of aging to 0.69, close to Bryan Johnson’s scores.
9:00 Who looks younger? Bryan Johnson (22 August 1977)? Or Tom Brady (3 August 1977)?
Nick’s source paper is linked below.
https://www.nature.com/articles/s43587-024-00793-y
Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial
Sample size is 777.
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Good question. The brain like all our other organs requires a variety of fluid flows. Blood and CSF are the 2 fluids that come to mind.
Loss of elastin affects circulation as the arteries lose their elasticity.
Elastases and elastokines: elastin degradation and its significance in health and disease
https://www.tandfonline.com/doi/full/10.1080/10409238.2020.1768208
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I was just trying to give you some hope 
120 is still the upper limit for lifespan, 140 is highly speculative but people don’t want to deal with the clock winding down.
Speaking of clocks, they deceive us and give us false hope. As an analogue clock runs in never ending circles, and a digital clock constantly repeating numbers, even the sun and the stars offer false hope. These are never ending indicators of time and life passing.
If humans were born with an hour glass in their chest that they could see and watch the very limited sands of their life running out, they might do things a bit differently. Or they may not. When that hour glass is new, and full to the brim it may seem unlimited. But we know it’s not.
Many of us on this forum are at the age where our peers are passing. When I see people 50, 60, 70 passing and I think about being in my 70th year at the age of 69, I often wonder how much time I have left. Will I hit the stat average of 81?, if that is my fate, I have 12 years left.
Is it now time for me to “retire” and sit back in my rocking chair or to engage more fully in the life I have left?
I’m going for the engaged approach, as all the members of this forum have also chosen
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Dr.Bart
#568
Again, there is no solid evidence for that, it’s all just speculations based on some theories and few case studies, so basically scraping the bottom of the scientific barrel.
I’m going for the engaged approach
I agree with all that, I am not sure what has to do with making blanket statements about the upper limit for human lifespan ? I would feel very lucky to live with mostly intact cognition to the age of 100.
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Not a very strong argument for your position LoL!
The elastin problem has been studied extensively and is very well understood by people much smarter than me. We know how elastin is lost, we know how long it takes to run out of it, we know it’s not replaceable systemically, those are scientific facts. As far as how elastin affects lifespan, it’s pretty simple logic, we die without it. Period, end of story.
So until there is a solution to the elasitin problem, human lifespan is rate limited to 120 years by this one factor. You can disagree with that all you want but you have not brought anything to the discussion that changes the established facts on elastin.
There are many other factors that limit how long humans can live, elastin is probably the hardest one to solve. When this problem is solved, this may allow for life to be longer than 120 years. Until then increasing health span is the only thing we can do.
I hope you do reach the century mark, it’s a good goal.
In the mid 90’s I was at a SNF in the SeaTac area, taking pictures of bedsores and saw a “leader board” with 6 people 100 and up, the oldest was 104. This was a Japanese only facility and very well run. The staff were very proud of their centenarians. I got to meet 2 of them.
I’ve been in over 200 SNF’s and had never seen a “leader board” like that. It was very cool
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Dr.Bart
#570
I don’t have a position on max age limit. Some scientists don’t believe there is a limit. There is as scant evidence for 140 as there is for 120.
In medieval England life expectancy was 31 years, once you made it to 25 then average became about 51 years old. The records were very poor back then but living in to 80’s was rare. Maximal lifespan was probably around 90. Now 600 years later, same place average age is 80’s and maximal lifespan recorded was 115. So that’s about 25-30 year shift. All mostly due to proper nutrition and sanitation.
What makes you think that we achieved maximal life span in 21 century when medicine is still in its toddler stage? We cannot cure most diseases, we can only manage or lessen the impact of most of them.
The elastin problem has been studied extensively and is very well understood by people much smarter than me. We know how elastin is lost, we know how long it takes to run out of it, we know it’s not replaceable systemically, those are scientific facts.
I am NOT discounting your research of the elastin pathophysiology but I would be careful with this dogmatic approach. Science is full of dogmas and myths that were disproven. We used to think neurons cannot regenerate once they are set in place in humans. There may be simple a solution for the elastin problem that we maybe already have implemented. Just like sanitation prevented millions of deaths or fluoride increased dental health. Again, unless you have a controlled human study, you cannot be certain.
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JuanDaw
#571
From Neo’s post 41 at the thread below:
(Bryan) “My speed of aging has also reduced even further to a .64 - a new personal best, and lower than 99% of 20-year-olds.”
Compare that to .69 with Omega 3 alone, at 1g/day.
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I’ve been taking 1gm+ of Omega 3 a day for 20 years. With my first DNAm test 5 years ago my “age” was 8 years younger. Maybe that was something that helped me be lower than “average”?
Over the last 4 yeas my DNAm results did start changing when I started our senolytic program 5 years ago and as I’ve added more "things’ it has continued to improve.
My biggest improvement in the DunedinPACE happened when I started GLP1-R’s nearly 2 years ago.
That is also when all my other blood tests became the best I’ve had in 15 years.
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Neo
#573
Just fyi that he is now sub 0.5
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JuanDaw
#574
Not that I put any value in aging clocks. But the figures show that substantial improvement by that measure, may be achieved with more economical interventions. The paper Nick Norwitz cites states:
Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge.
Will have to wade through the paper for the figure with respect to “additive benefits” of Omega 3, plus Vit D, plus exercise. I do take 2,000 iu of Vit D. My Omega 3 intake comes from sardines.
The longevity benefit of Omega 3 was also discussed in the thread below.
The paper cited in the thread is linked below.
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I think that if you are on this forum you are not going to hit the average age of 81, you are going to hit the average age of affluent Americans which is 92.
Add in Rapamycin, SGLT2IS, Omega 3s, etc… I think 100 is a very realizable goal. After 100 it gets dicey fast.
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What we know is that elastin requires cells with higher efficiency to generate the right elastin splices. It is also possible to adjust splicing.
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