Stem cell-derived extracellular vesicles/exosomes [MSC-exosomes] can reduce epigenetic age by 15 years - anyone tried them?

I hear there are clinics in Roatan that do it (I might try soon). I don’t know the risks though…

https://www.nature.com/articles/s41598-022-17944-z

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MSC-exosomes contain at least 170 different miRNAs [22] and 304 proteins [23], along with an indefinite number of DNAs, mRNAs and metabolites [12]. Because they contain a large number of bioactive molecules, MSC-exosomes have attracted great interest in the field of regenerative medicine. Accordingly, numerous studies have attempted to assess whether the infusion of MSC-exosomes can serve as an alternative strategy to repair tissue damage, and emerging results have mostly revealed that MSC-exosomes have therapeutic effects similar to those of their parental MSCs [24]. Moreover, MSC-exosomes have several advantages over MSCs. (i) MSC-exosomes are long-lasting and can be stored at −80 °C without affecting their biological functions [17], whereas cryopreserved MSCs exhibit impaired immunoregulatory and pro-regenerative properties compared with fresh MSCs [25]. (ii) The membranes of MSC-exosomes are enriched in sphingomyelin, cholesterol, ceramide and lipid raft proteins, enabling MSC-exosomes to spread in vivo regardless of biological barriers, such as the blood-brain barrier [26], for example, even when they are delivered via an intravenous injection, MSC-exosomes can be detected in injured neurons in the brain [27]. (iii) Infusion of MSC-exosomes elicits minimal immune rejection due to their complete lack of expression of major histocompatibility complex (MHC) molecules [28,29], which prevents their rapid clearance by host immune cells. For instance, MSC-exosomes were found to remain in a recipient for a significantly longer time than MSCs after infusion [28,30], indicating that they can perform their biological functions in vivo for a relatively long time. (iv) Infusion of MSC-exosomes can avoid several stem cell-associated challenges, such as the risk of spontaneous tumorigenesis induced by MSCs [31,32]. (v) The potential secretion of exosomes by MSCs can be impacted by various factors. For example, maintaining MSCs in a physiological state in an in vitro culture system can impact their production of exosomes with a specific phenotype in terms of biological activity [33]. Notably, although incubating MSCs with an IFN-γ plus TNF-α mixture in vitro reduced their proliferation, the production of exosomes was not adversely affected [28,34].

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https://www.nature.com/articles/d41586-020-01770-2

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I had an exosome treatment for my “bad” knee–along with PRP and my own stem cells–in an attempt to avoid a knee replacement. It worked, and I also think the anti-inflammatory effect of rapamycin is now playing a big role in me having a functional knee. The MRI previous to all this showed " vast areas of cartilage loss, a large lateral osteophyte, torn meniscus, bone edema, and a Baker’s cyst." It was painful to walk. Now I walk, swim, & ride my horse with no problem. I have a little creakiness where that bone spur is, but it’s no problem.

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I’ve been wanting to try it ever since I found out what exosomes were.
If I had enough cash I’d set up my own lab to do it just for myself.
The trouble with commercial labs is you trust that they’re doing the right thing…but you have no way of knowing if they are.

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There’s a telegram group called research collective where they discuss it - they also had MUCH increased energy after it too…

I might meet some ppl in it when I’m in Roatan

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Would love to hear more about this

I was searching on knee pain and found your post. I have pretty much the exact same issue. Supartz helped some but I need a bigger gun. I have had surgery on both knees. I started working out again with regularity and that damn bakers cyst flared up and it’s painful. What’s your latest findings on the procedure? Does insurance even cover this? I pay out of pocket for Supartz it’s cheaper than the insurance cost it’s not long term just like getting a little oil from Oil Can Harry in my joint.

Anyone try peptide BPC 157 for joint pain? Other suggestions?

come to the GARM CLINIC

Hi Barbara,

I know about painful knees!

I did PRP, then PRP with stem cells (my own, at that time, from abdominal fat–I was less than 70 at the time, (67) so my stem cells were considered viable–now I’m 72).

Then about 6 to 12 months later, I got exosomes injected into the knee. No immediate effect from the exosomes, but over time my knee got better and better. I was also injecting BPC 157 SQ around the knee area–I think I did that for a year.

What has truly helped my severe, progressive osteoarthritis of the back and knees, has been sirolimus–I didn’t really see results with the sirolimus until I had been on it 6 months–then most of my pain and stiffness went away, also including my gum disease, my dry eye, & my hearing loss–all those markers of aging.

Anyway, I had just retired at 67 and had a health care account from my left over sick time, which is how I paid for most of this.

I probably spent 8 to 10k on my knee.

The hyurlonic acid treatment sounds good–what does it cost?

All the best to you

Suzanne

Sent from my iPhone

On Dec 8, 2022, at 7:18 AM, Barbara via Rapamycin Longevity News noreply@www.rapamycin.news wrote:

45x45 Babster
December 8

I was searching on knee pain and found your post. I have pretty much the exact same issue. Supartz helped some but I need a bigger gun. I have had surgery on both knees. I started working out again with regularity and that damn bakers cyst flared up and it’s painful. What’s your latest findings on the procedure? Does insurance even cover this? I pay out of pocket for Supartz it’s cheaper than the insurance cost it’s not long term just like getting a little oil from Oil Can Harry in my joint.

Anyone try peptide BPC 157 for joint pain? Other suggestions?


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Well on the knee cost of the Supartz, it was about 180 out of pocket. I’m not so sure now, I have a new plan, will be on Medicare in July so I’m not sure what that will look like. This time the “insurance approved” injection is Euflexxa and I spent a good part of my day trying to figure what it actually will cost me and I’m still confused. It helps but it doesn’t fix anything. Just some lube in between the gaskets.

On the Rapa front, I have hopes. I just went to 6 mg -10 weeks ago which is what I’d suspect is a more optimal dose for me. In the Covid era I became more sedentary, drank more wine and I’m really making changes because I got lazy and unhealthy (Cheetos never tasted so good). I’m pretty sure I could be the biggest f’up in this group based on the posts I read.

I’m loving Pilates, had a dusty reformer that I am totally in love with. Gentle, toning, I can do this every day!

I definitely have some belly fat, what a good use of recycling!! I would like to have a conversation with a doctor that did your knee. It’s challenging to find this. I’m in the Albuquerque area.

Thanks for your reply.

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Dear Babster,
Dr Jimmy Heubert, Sports and Spine Clinic, Tualatin Oregon, previous orthropedic surgeon, now does regenerative medicine. I don’t think he is on the rapamycin band wagon–not sure why not.
I would probably take a break from rapamycin if I got exosomes or stem cells or PRP–probably just to keep it simple, uncomplicated, and to see what did what.
He might be able to steer you to someone in your area.
all the best to you,
Suzanne “coop”

Saturday, December 24, 2022

Is There Hope in the Fight Against Aging?

Mauricio Wajngarten, MD

December 19, 2022

For many years, it has been believed that the aging process is inevitable and that age-related diseases cannot be prevented or reversed. For example, the US Food and Drug Administration (FDA) does not recognize aging as an indication for drug approval because there are no markers to determine whether possible treatments have a significant impact on the hallmarks of aging.

The field of geroscience aims to find ways to change this by delaying the onset of age-related diseases or by extending the life span. On May 19, 2021, experts in geroscience met virtually at a symposium of the New York Academy of Sciences. Presentations and discussions with experts in the field showed that remarkable advances have been made in understanding the mechanisms underlying biological aging. Those mechanisms contribute to the vulnerability of older adults. The presentations focused identifying biomarkers of aging and on the search for interventions to prevent and treat age-related diseases.

Perspectives from this meeting were published in a report.

An Abridged Glossary

Senescent cells: These are old cells with irreversibly damaged DNA; they strongly resist apoptosis. Thus, they are not eliminated and continue to secrete pathogenic proinflammatory molecules.

Senolytics: This is a class of compounds that promote the removal of senescent cells from the body.

Autophagy: This is a process that promotes protein degradation, which is attenuated with aging and that impedes the aggregation of proteins harmful to cell function, particularly those of the central nervous system.

Proteostasis: This is the dynamic regulation of protein homeostasis.

Epigenetics: This is the field of biology that studies phenotype changes that are not caused by changes in DNA sequencing and that continue to affect cellular division.

Metabolome: This refers to small molecules that make up the building blocks of all organismal features, from cell membranes to metabolic cycles to genes and proteins.

Translational research: This involves applying primary research results to clinical research, and vice versa.

Possible Research Topics

Senescence not only occurs with age but also drives aging. At the meeting, evidence was provided that senescent cells may exacerbate the clinical course of older adults in cases of infections (eg, COVID-19) as they lead to cytokine storms. Experiments on old mice that have undergone genetic modification of senescent cells or the administration of “senolytic cocktails” composed of dasatinib plus quercetin protected the animals from the effects of viral infections. This finding corroborates the idea that factors involved in biological aging increase vulnerability and could be modified through treatment.

Cite this: Is There Hope in the Fight Against Aging? - Medscape - Dec 19, 2022.

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this is REALLY GOOD. also apparently unpasteruized dairy milk has DAIRY EXOSOMES which is why dairy farmers are so huge/high IGF’d

btw the reductions in epigenetic age are temporary. they are, after all, just PBMCs…

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Rejuvenating effects of young extracellular vesicles in aged rats and in cellular models of human senescence

Rejuvenation of an old organism was achieved in heterochronic parabiosis experiments, implicating different soluble factors in this effect. Extracellular vesicles (EVs) are the secretory effectors of many cells, including cardiosphere-derived cells (CDCs) with demonstrated anti-senescent effect. 1. To determine the role of EVs (versus other blood fractions) on the rejuvenating effect of the young blood. 2. To evaluate the anti-aging properties of therapeutically administered EVs secreted by young-CDCs in an old organism. Neonatal blood fractioned in 4 components (whole blood, serum, EV-depleted serum and purified EVs) was used to treat old human cardiac stromal cells (CSPCs). CDCs were generated from neonatal rat hearts and the secreted CDC-EVs were purified. CDC-EVs were then tested in naturally-aged rats, using monthly injections over 4-months period. For validation in human samples, pediatric CDC-EVs were tested in aged human CSPCs and progeric fibroblasts. While the purified EVs reproduced the rejuvenating effects of the whole blood, CSPCs treated with EV-depleted serum exhibited the highest degree of senescence. Treatment with young CDC-EVs induce structural and functional improvements in the heart, lungs, skeletal muscle, and kidneys of old rats, while favorably modulating glucose metabolism and anti-senescence pathways. Lifespan was prolonged. EVs secreted by young CDCs exert broad-ranging anti-aging effects in aged rodents and in cellular models of human senescence. Our work not only identifies CDC-EVs as possible therapeutic candidates for a wide range of age-related pathologies, but also raises the question of whether EVs function as endogenous modulators of senescence.

Open access journal:

https://www.nature.com/articles/s41598-023-39370-5

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Exosomes and their Potential for Rejuvenation

Posted on August 6, 2023

Extracellular Vesicles (EVs) have only been studied in the 21st century. Think of them as natural lipid nanoparticles, or endogenous viruses. They transmit information around the body and they’re small enough to be exhaled and carried in the air to communicate with other individuals and even other species. EVs are encapsulated in fats that facilitate entry into cells, and inside they contain proteins, RNA, DNA, lipids — all of which carry information. EVs are a universal biological language, a barely-explored medium of communication.

Last week, an extraordinary paper was published demonstrating the rejuvenation potential of EVs from very young animals injected into old animals. The authors come from Smidt Heart Institute in Los Angeles, and their primary field is cardiology, not gerontology, so they focus on heart-derived EVs and benefits for rejuvenating the heart. But the benefits they observe go well beyond the heart and include lifespan in rodents and rejuvenation of human cells from rat-derived EVs.

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I finally got around to reading the paper. It’s really impressive. This seems to tally with Harold Katcher’s E5 experiments. The cross species affect is fascinating, it seems that there’s also some link to Michael Levin’s work. That young cells can reprogram cells across species seems to point to an overarching mechanism or collective intelligence.
If exosomes are the source of the rejuvenation then it’s not that difficult to get hold of them. There are lots of clinics offering products, although it’s hard to know where they source it from.
There are already a couple of clinical trials underway (thanks to COVID)
They’re also a lot cheaper than stem cells.

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Another recent and relevant paper:

Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice

We have previously demonstrated that circulating extracellular vesicles (EVs) are essential to the beneficial effect of young serum on the skeletal muscle regenerative cascade. Here, we show that infusions of young serum significantly improve age-associated memory deficits, and that these effects are abolished after serum depletion of EVs. RNA-seq analysis of the choroid plexus demonstrates EV-mediated effects on genes involved in barrier function and trans-barrier transport. Comparing the differentially expressed genes to recently published chronological aging clock genes reveals a reversal of transcriptomic aging in the choroid plexus. Following young serum treatment, the hippocampal transcriptome demonstrates significant upregulation of the anti-aging gene Klotho, along with an abrogated effect after EV depletion. Transcriptomic profiling of Klotho knockout and heterozygous mice shows the downregulation of genes associated with transport, exocytosis, and lipid transport, while upregulated genes are associated with activated microglia. The results of our study indicate the significance of EVs as vehicles to deliver signals from the periphery to the brain and the importance of Klotho in maintaining brain homeostasis.

Open access Paper:

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Following on from this. Harold Katcher explains a bit more about his treatment. Again, really fascinating. It seems that some of the most recent papers on exosomes point to a conserved mechanism and maybe all we need as Dr. Katcher mentions is all the exosomes created by juvenile mammalian blood.

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My main concern is the increase in growth hormone and IGF1, one person mentions massively increased libido…

Healing times are way better, so they are good to inject in after injury, but like, otherwise…

there’s a book by Christian that is really good…

https://kimeralabs.com/the-utilization-of-human-placental-mesenchymal-stem-cell-derived-exosomes-in-aging-skin-an-investigational-pilot-study/ has a formualtion that has IGF-binding-proteins