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My random notes/stream of consciousness thread


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Since I know others might appreciate my output.

Magnesium glycinate seems to be a killer supplement cuz it has BOTH magnesium and glycine.. It's hard to regularly dose too many supplements, and the core is taurine+carnosine+curcumin/piperine+B12+D+modafinil+green tea powder

Edited by InquilineKea
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"My random notes/stream of consciousness thread" - I thought every thread you post is random/stream of consciousness? 

Why is it a killer supplement? What are the benefits of supplementing with magnesium if your diet is good (good diet applies to most on these boards)? Why is glycine a good thing to supplement with - we just saw a lengthy thread from Ron asking questions about glycine and it's a very complicated story with possible dangers of cancer when supplementing - you reference nothing of that complexity, you just make a random assertion with nothing behind it. Why is the "core" taurine+carnosine+curcumin/piperine+B12+D+modafinil+green tea powder? Seems a random collection of supplements with very, very complicated stories - you just mashed them together with nary a context... like stream of consciousness.

In other words, as always, you drop these random questions or assertions with nothing behind them and no in-depth research and expect - I don't know what - that others will do all the research for you? Just random, random stuff. But whatever makes you happy - I'm just astonished to see you select this particular thread to call "random" and "stream of consciousness" when for the life of me I can't tell the difference - in the respect of randomness - from any other thread you post. Of course, it might just be for the club of those who "appreciate your output". 

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They help bring up threads that others find useful! Even if my posts are short, I frequently use the search feature so I'm highly aware of what's new to people and what isn't, so my threads bring up a lot of novel content, esp b/c this is one of the best high-quality boards of aging content, but there are still A LOT of missing (but still important) threads

Edited by InquilineKea
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OMG, Gordo, that is super on the mark! I now am 100% convinced InquilineKea is an AI bot! The giveaway can be found in those experiments with bots trying to pass the Turing Test - the characteristic of those bots is that they never supply any new information or have any depth, but rather they "ask" questions - simply grab something a human says and turn it into a question so it looks sentient. 

Human: I had to solve a really difficult math problem to make this work.

Bot: How did that make you feel?

Human: It made me feel very tired.

Bot: Why did it make you feel tired?

And so on.

This is InquilineKea in a nutshell - pointless questions with no followup and random remarks, and no original contribution. Mostly "questions". Gordo, you're a genious!

Edited by TomBAvoider
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OK Guys,

You got me. Inquilinekea is one of my bots. 🙂

But seriously. We've been discussing who is Alex K Chen (aka InquilineKea) and why he asks so many questions for years. Here is one example. There is even a thread about him that I started in 2016 on the admin/moderator board for these fora called "Mr. Questions - Alex K Chen (aka InquilineKea)". We concluded he is harmless, and very occasionally makes thoughtful contributions rather than just asking questions (e.g. here). He was even active on the CR mailing list back to at least 2012 before these fora were created (search "simfish" Tom).

We've had it easy for the last few years since Alex went quiet here around 2017. But he's continued to ask lots of questions (and answer quite a few) on Quora. His Quora profile shows he has asked 62K questions since 2013. Here is a good one. He's also very active on Reddit.

I've even communicated with Alex via email. He asked if we might meet up during a visit he made to Pittsburgh a couple years ago. It didn't work out so I couldn't verify his humanity first hand. 🙂

If he's a bot, he is a very good one. I for one welcome our new AI overlords. 🙂

--Dean

 

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  • 4 weeks later...

He does ask a lot of questions.. 

When I've tried to communicate with him and ask some back, he almost never responds. 😉

Must be artificially intelligent 😎

Edited by Matt
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2 hours ago, Matt said:

Must be artificially intelligent

Funny, I think of InquilineKea as a "she."  Maybe like Alicia Vikander in Ex Machina :D

LOVE the paper though??!  The paper talks about random damage, which I also have thought of as a given, in general, in addition to direct damage.  But what do I know? 

The de Grey reference is, if anything, a negative, IMO.

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2 hours ago, Ron Put said:

The paper talks about random damage, which I also have thought of as a given, in general, in addition to direct damage.  But what do I know? 

It's not about "random damage",  but specifically   the  multiple ways aging and disease result from "the accumulation of intra-intermolecular covalent bonds (crosslinks) between molecules with slow turnovers, such as collagen and elastin of the extracellular matrix (ECM) "

This is not a new topic, of course, but the authors go into a lot of dimensions that haven't been discussed that much.

FWIW, I'm not a a huge fan of Aubrey de Grey  myself.   Particularly wrt the business aspect of his endeavors.  But I try to assess his scientific contributions individually and on their own merit,  or lack of it, apart from his broader anti-aging philosophy and business model.

In any case,  de Grey merely made some " helpful comments on the manuscript ",  so it would be silly to draw any conclusions from that acknowledgment, even from an ad hominem perspective.

Perhaps  your anti-Russian attitudes  (well noted in the Calment controversy discussion)  have predisposed you against this paper?   Take a look at the full text;  there are some interesting ideas there.

Edited by Sibiriak
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✌
1
8 hours ago, Sibiriak said:

It's not about "random damage",  ...

This is not a new topic, of course, but the authors go into a lot of dimensions that haven't been discussed that much.

... Perhaps  your anti-Russian attitudes  (well noted in the Calment controversy discussion)  have predisposed you against this paper?   Take a look at the full text;  there are some interesting ideas there.

Hm, but it is about random damage and it's presented as something groundbreaking:  "However, the list of proposed hallmarks is missing the stochastic non-enzymatic modification of long-lived macromolecules. In this review, we summarized all evidence that it is in fact one of the primary, causative hallmarks."  I perused the paper and it is a good overview, but I just don't see anything new in it, or at least in the part that they state is new.

Nothing to do with it being Russian.  And please don't assume that because I find the current leadership of Russia poisonous to its neighbors and to the world community, I hold anti-Russian views.  On the contrary, I am a Russophile, in that I admire Russia's very significant cultural and scientific contributions to our world, and I have many close Russian friends.

If anything, I feel disappointed and sad about Russia, because I really thought that things may have been different if the West had acted differently after the fall of the USSR.  The US has not had a coherent strategic vision since the mid-1990s when Clinton essentially put Harvard's Institute for Int'l Development in charge of America's Russia policy and USAID, with little to no oversight.  People like Summers propped up budding oligarchs like the Chubais clan and paved the way for Russian nationalism and distrust of Western "experts."  And successive US administrations have not done better.  The US should have promoted transparency in Russia, and helped integrate Russia into the world community, but it failed to do so.  Swiss, German and British banks viewed Russia (and much of Eastern Europe) as a place they could make a lot of money and not play by the rules applicable within Western Europe.  It was a recipe for disaster and we got it, in the shape of Putin and Russian nationalism.

Anyway, I am digressing and this is not the place for it, but I find what happened in Russia really depressing, even though I like visiting.

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On 7/4/2020 at 12:45 AM, Matt said:

He does ask a lot of questions.. 

When I've tried to communicate with him and ask some back, he almost never responds. 😉

Must be artificially intelligent 😎

you never respond to me either!!!! and i wanted to see you in britain!!!

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APR 22, 2020, 4:41 PM

You named the group CANONICAL AGING PAPERS.
You named the group CANONICAL AGING PAPERS (mechanistic, upstream of other factors).
You added Diana Leung to the group.
Alex K. Chen
Alternative splicing in aging and age-related diseases
You added Rob Sheko to the group.
You named the group CANONICAL AGING PAPERS (mechanistic, upstream of other factors, highly generalizeable and less ad hoc).
Alex K. Chen
longer mRNAs are more prone to disruption - i wonder which proteins have longest mRNAs apart from titin
clonal hemapoetesis
Altering nuclear pore complex function impacts longevity and mitochondrial function in S. cerevisiae
Alex K. Chen
Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells. Toyama BH, Arrojo E Drigo R, Lev-Ram V, Ramachandra R, Deerinck TJ, Lechene C, Ellisman MH, Hetzer MW. J Cell Biol. 2019 Feb 4;218(2):433-444. doi: 10.1083/jcb.201809123. Epub 2018 Dec 14. PubMed [citation] PMID: 30552100 PMCID: PMC6363465
Alex K. Chen
E2/E3 protein ligases, methyltransferases, acetyltransferases, kinases VS all proteins involved in DNA damage response
changes in nucleolar size with age (it seems nucleasomes keep aggregating)
The emerging role of alternative splicing in senescence and aging is a masterpiece
Advances in targeted degradation of endogenous proteins

APR 22, 2020, 7:32 PM

You added Cesar Ruiz de Castilla to the group.
Alex K. Chen
The Mechanobiology of Aging Jude M. Phillip,#1,2 Ivie Aifuwa,#1,2 Jeremy Walston,3 and Denis Wirtz1,2,4
❤1
Cesar Ruiz de Castilla
Cesar Ruiz de Castilla
Will read this looks interesting
*read as many of these
Alex K. Chen
thanks! 🙂 i think these are among the most impt/SO WELL WRITTEN
friend denis!
Olafur Pall Olafsson
Olafur Pall Olafsson
good initiative Alex. I got to read more of these later
Amit Tal
Amit Tal
I’ll be doing the same, thanks so much
Alex K. Chen
Alex K. Chen <simfish@gmail.com>

Fri, Nov 8, 2019, 7:39 PM

to David
https://www.facebook.com/odinokov lists many of them - he has been
on a roll lately

Ben Best for sure [not academic papers but websites].

JP de Magalhaes has a cool website but his papers aren't the best
(biostatistics is messy and papers are often published before the data
is perfected and you often tease out mRNA that you like barely
understand)

i'll look in my pubmed favorites

On Fri, Nov 8, 2019 at 7:35 PM David Bieber <david810@gmail.com> wrote:
>
>

Alex K. Chen <simfish@gmail.com>

Fri, Nov 8, 2019, 7:39 PM

to David
the evolutionary biology people are often very clear if not consistently correct

Alex K. Chen <simfish@gmail.com>

Fri, Nov 8, 2019, 7:40 PM

to David
VADIM gladyshev
Alex K. Chen <simfish@gmail.com>

Fri, Nov 8, 2019, 7:44 PM

to David
I like https://www.ncbi.nlm.nih.gov/pubmed/16533927 a lot they
actually are good at guessing at whatever the mechanisms are

Alex K. Chen <simfish@gmail.com>

Fri, Nov 8, 2019, 7:46 PM

to David
so like, i like steve austad and the other evolutionary biology
people. also daniel promislow. they don't think at the highest level
[in the way that people who do information-theoretic/information
theory/shannon communication theories of aging do it] but it's good
enough for me to quickly understand it.
Alex K. Chen <simfish@gmail.com>

Fri, Nov 8, 2019, 7:47 PM

to David
also J Vijg
Alex K. Chen <simfish@gmail.com>

Fri, Nov 8, 2019, 7:51 PM

to David
also like caleb finch is THE walking encyclopedia on aging but he's
oldr so he might not be as up to date on the newer details

certainly there has to be someone who is a walking encyclopedia of all
the post-translational oxidative/carbonyl modifications that can
affect proteins and how they affect the shape of said protein
Alex K. Chen
Johnson, A. A., Shokhirev, M. N., Wyss-Coray, T., & Lehallier, B. (2020). Systematic review and analysis of human proteomics aging studies unveils a novel proteomic aging clock and identifies key processes that change with age. Ageing Research Reviews, 101070. doi:10.1016/j.arr.2020.101070
You added Sarah Constantin to the group.

APR 23, 2020, 2:24 AM

MAY 13, 2020, 3:20 PM

You added Emanuele Ascani to the group.

MAY 13, 2020, 5:55 PM

You added John Wentworth to the group.

JUN 2, 2020, 3:23 AM

You added Aahan Rashid to the group.

WED 9:25 PM

You added Vienna Thomas to the group.
Alex K. Chen
You added José Luis Ricón to the group.
 
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10 hours ago, InquilineKea said:

You never respond to me either!!!! And I wanted to see you in Britain!!!

You have to go right back to the beginning...  Maybe I stopped responding because you didn't respond to my follow up questions?

You mean by going to Oxford or London? I don't remember the circumstances, but it was probably more to do with lack of money at the time than anything else. I barely had any work at the time.

I have met people in IRL that I've spoken to online, but I've also had some reciprocal effort and communication from them. We barely ever even spoke to each other. 

But even so, I still didn't have the money to be using it on travelling at the time.

Edited by Matt
Clarification
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  • 2 weeks later...

 

shared a memory.
tSopoons1ohcred
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shared-story-header-left.png
2 Years Ago
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JtSpdouSoelncsoltsiy 25har,n r2e018idf
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Some takeaways from The Handbook of Biomarkers. Jain, K.K. (2017):
***
Biomarkers for determining biological age:
- Epigenetic clocks
- Telomere length and attrition [Fouquerel, E. et al. Oxidative guanine base damage regulates human telomerase activity. Nature Structural & Molecular Biology 23, 1092–1100 (2016).]
[however, Van Ly, D. et al. Telomere-loop dynamics in chromosome end protection. (2018).]
- Transcriptomic predictors
- Proteomic predictors
- Metabolomics-based predictors
- Composite biomarker predictors
***
Biomarkers of healthy aging:
- Physiological functioning (i.e., cardiovascular function, lung function, glucose metabolism, and musculoskeletal function)
- Endocrine function (i.e., hypothalamic-pituitary-adrenal [hpa] axis, sex hormones, growth hormones)
- Physical capability (i.e., strength, balance, dexterity, locomotion)
- Cognitive function (i.e., memory, processing speed, executive function)
- Immune function (i.e., inflammatory markers)
- Memory, executive function, and speed of processing information
Biomarkers as predictors of mortality with aging:
- C-reactive protein
- White cell count
- NT-proBNP (N-terminal pro brain natriuretic peptide)
Healthy Aging Index:
- Systolic blood pressure
- Pulmonary vital capacity
- Serum creatinine (for kidney function)
- Fasting glucose
- Cognitive function (based on the modified Mini-Mental Status Examination)
Also,
- Cholesterol fractions
- Erythrocyte sedimentation rate
- Fibrinogen
- Granulocytes
- Homocysteine
- Intercellular adhesion molecule-neutrophils
- Osteoprotegerin
- Procollagen type III aminoterminal peptide
- Serum uric acid
- Soluble urokinase plasminogen activator receptor
- Tissue inhibitor of metalloproteinases 1
- Tumour necrosis factor receptor II
Physiological measurements:
- Core body temperature
- Blood pressure
- 24-hour energy expenditure
Endocrinological biomarkers:
- Dehydroepiandrosterone sulfate
- Insulin levels
- Hypothalamo-pituitary-thyroid axis (thyroid hormone levels)
Genes as biomarkers:
- DNA damage
- DNA methylation
- Variants located near TERC gene
Mitochondrial mutations:
- mtDNA mutations
[- NUMT from Muradian, K. K., Lehmann, G. & Fraifeld, V. E. NUMT (‘New Mighty’) Hypothesis of Longevity. Rejuvenation Research 13, 152–155 (2010).]
Metabolomic biomarkers:
- 1,5-Anhydroglucitol
- Dimethyl-guanosine
- Acetyl-carnosine
- Carnosine
- Ophthalmic acid
- UDP-acetyl-glucosamine
- N-acetyl-arginine
- N6-acetyl-lysine
- Pantothenate
- Citrulline
- Leucine
- Isoleucine
- NAD+
- NADP+
Protein biomarkers:
- Carbamylated proteins (carboxymethyl-lysine) and other Advanced glycation end products (AGEs)
- Humanin
Proteomic Biomarkers of Muscle Aging:
- Sarcomere and cytoskeleton-related (myosin light-chains, troponin, ankyrin repeat domain-containing protein-2, vinculin, FHL3 four and a half LIM domains 3)
- Calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins)
- Cytoprotection (catalase, peroxiredoxins)
- Ion homeostasis (carbonic anhydrases, selenium-binding protein
- Detoxification (aldo-keto reductases, aldehyde dehydrogenases)
***
The American Federation for Aging Research has proposed the following criteria for a biomarker of ageing:
1. It must predict the rate of ageing. In other words, it would tell exactly where a person is in their total life span. It must be a better predictor of life span than chronological age.
2. It must monitor a basic process that underlies the ageing process, not the effects of disease.
3. It must be able to be tested repeatedly without harming the person, for example, a blood test or an imaging technique.
4. It must be something that works in humans and in laboratory animals, such as mice. This is so that it can be tested in lab animals before being validated in humans.
from MARK-AGE biomarkers of ageing.
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tSp2onnsuotrhed
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How have I completely missed the importance of erythrocyte senescence in all of my studies? .....
 
 
 
 
 
 
 
 
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I've studied T-Cell Senescence, hadn't thought of Red blood Cell Senescence, good share https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636159/
 
T cell anergy, exhaustion, senescence and stemness in the tumor microenvironment
NCBI.NLM.NIH.GOV
T cell anergy, exhaustion, senescence and stemness in the tumor microenvironment
T cell anergy, exhaustion, senescence and stemness in the tumor microenvironment
 
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I wonder what your thinking. The degradation of ACE2 receptors via Sars-Cov2 brings the endothelial lining into sharp focus, as well as thrombosis factors, and Sars-Cov2 attacking T-Cells via CD147 brought T-Cell Exhaustian and Senescence into sharp focus for me. So I'm curious about this shift in focus to RBC Senescence. What are you thinking? 🙂
 
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Novel coronavirus attacks and destroys T cells, just like HIV
NEWS-MEDICAL.NET
Novel coronavirus attacks and destroys T cells, just like HIV
Novel coronavirus attacks and destroys T cells, just like HIV
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NATURE.COM
RETRACTED ARTICLE: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion
RETRACTED ARTICLE: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion
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It is my understand that red blood cells are replaced every few weeks. They wear out and lyse because they have no nucleus and very little in the from of protein synthesis.
Senescence in the cells that form red blood cells (hemocytoblasts) is probably important when they produce fewer or defective rbc's but the red blood cells themselves are wearing out and getting replaced in young and old alike on time scales much shorter that aging.
 
Measurement of Red Cell Lifespan and Aging
NCBI.NLM.NIH.GOV
Measurement of Red Cell Lifespan and Aging
Measurement of Red Cell Lifespan and Aging
 
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Oops, mistake, a few months not a few weeks, ne at the less the production and removal of red blood cells is where the aging will occur rather than in the cells themselves.
So old blood blood cells is an indication that they are not being cleaned out properly by the spleen, while fragile and defective cells could indicate poor health of the stem cells or problems with environment of the cells like high blood sugar.
 
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Important in what aspects? I'm curious to know because as Michael pointed out RBCs are replaced regularly and their life span is a relatively constant 120 days and does not differ much between humans so the age-distribution of the RBCs should be pretty constant. If you're thinking this has any implications for individual COVID-19 susceptibility I would think it has little effects unless somehow people can have a higher proportion of senescent RBCs without their average life span being significantly shorter than 120 days. Did the paper say anything about this?
 
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On a related note. If senescent RBCs play some kind of role in increasing risk for COVID-19 severity then donating blood regularly could be preventative inasmuch as it reduces the average age of the RBCs. Just throwing this out. I don't know if RBC senescence has anything to do with COVID-19 since I didn't read the full paper.
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JntuolooyldSr mtm2p1 hosrnsartlto h3:57 rdeASdM
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Are you getting old yet counting on the cellular reprogramming or metabolic fine-tuning as on your personal savior?
Blame yourself for wasting years believing that the cells can decide their fate freely from their environment (the long-lived components of the extracellular matrix) or some presumably nonrenewable intracellular components (such as the nuclear pore complex in post-mitotic cells).
The crosslinks accumulation changes viscoelasticity, surface topography and chemical composition of the ECM, which in turn affect not only the cellular response to various biophysical stimuli, such as force, osmotic pressure, stretching, and shear stress but also cause multiple cellular dysfunctions, including the stem cell pool depletion.
Fedintsev A, Moskalev A. Stochastic non-enzymatic modification of long-lived macromolecules - A missing hallmark of aging. Ageing Res Rev. 2020;62:101097. doi:10.1016/j.arr.2020.101097
 
 
 
 
36 Comments
4 Shares
 
Comments
 
 
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indeed, REJUVENATION SCIENCE IS NOT DELIVERING, because most researchers are breaking down the wrong doors!
 
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I wish you had a billion dollar budget.
 
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I believe that the solution would cost less than billion dollars https://www.longevity.technology/building-an-artificial-immune-system/
 
Building an artificial immune system - Longevity.Technology
LONGEVITY.TECHNOLOGY
Building an artificial immune system - Longevity.Technology
Building an artificial immune system - Longevity.Technology
 
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also I believe that the aging will be solved by not biologists and genetics but chemists and chemistry informatics
 
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Very interesting.
 
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yes, it looks more promising than the enzymes search conducted by David Spiegel's group and (attempted to be) commercialized by https://www.revelpharmaceuticals.com/
 
Revel Pharmaceuticals
REVELPHARMACEUTICALS.COM
Revel Pharmaceuticals
Revel Pharmaceuticals
 
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should there also be non medicals scientists involved? As the breakdown of crosslinks might be something for physicists? Like radiation or nano robots?
 
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though radiation making the ECM softer, it tears the collagen fibers across, not along. Not sure if such structural changes have any positive effect on the cellular fate
 
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I am sure if it is possible, it should be radically precise resonating ray.
 
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Clinical doses of radiation reduce collagen matrix stiffness - PubMed
PUBMED.NCBI.NLM.NIH.GOV
Clinical doses of radiation reduce collagen matrix stiffness - PubMed
Clinical doses of radiation reduce collagen matrix stiffness - PubMed
 
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вас тоже удивляет почему некоторые до сих пор не могут понять, что основа старения это химия, а биология лишь на подхвате
 
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