261 replies to this topic

[albedo]

"Post-translational epigenetic modifications take place in mouse neurons of the dentate gyrus (DG) with age. Here, we report that age-dependent reduction in H3K9 trimethylation (H3K9me3) is prevented by cyclic induction of the Yamanaka factors used for cell reprogramming. Interestingly, Yamanaka factors elevated the levels of migrating cells containing the neurogenic markers doublecortin and calretinin, and the levels of the NMDA receptor subunit GluN2B. These changes could result in an increase in the survival of newborn DG neurons during their maturation and higher synaptic plasticity in mature neurons. Importantly, these cellular changes were accompanied by an improvement in mouse performance in the object recognition test over long time. We conclude that transient cyclic reprogramming in vivo in the central nervous system could be an effective strategy to ameliorate aging of the central nervous system and neurodegenerative diseases."

https://www.cell.com...6711(20)30385-4

https://www.lifespan...ry-in-old-mice/

[albedo]

Was waiting for this: published in Nature on Dec 2, 2020 on OSK reprogramming:

 

Lu, Y., Brommer, B., Tian, X. et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature 588, 124–129 (2020). https://doi.org/10.1...1586-020-2975-4

 

"Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity^1,2,3. Changes to DNA methylation patterns over time form the basis of ageing clocks⁴, but whether older individuals retain the information needed to restore these patterns—and, if so, whether this could improve tissue function—is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity^5,6,7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo."

https://www.nature.c...0-2975-4#citeas

[albedo]

In case you missed it:

Partial Reprogramming Rejuvenates Human Cells by 30 Years

https://www.lifespan...ls-by-30-years/

https://www.biorxiv.....01.15.426786v1

 

[albedo]

Very informative interview by Rhonda Patrick to Steve Horvath, much work the time!

https://www.foundmyf...tm_medium=email

[albedo]

Very informative interview by Rhonda Patrick to Steve Horvath, much work the time!

https://www.foundmyf...tm_medium=email

 

my bad ... I meant: "much worth the time!"
 

[albedo]

Major work and important implications for the theory of aging:

 

"... aging is hard-wired into life through processes associated with development.  A large body of literature connects growth/development to aging starting with the seminal work by Williams 1957 11. This connection is also apparent when Yamanaka factor-mediated reversion of adult cells to embryonic stem cells is accompanied by resetting of their age to prenatal epigenetic age, matching their development stage 1..."

 

"...Collectively, these new observations support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species – a notion that was long-debated without the benefit of this new and compelling evidence..."

 

Universal DNA methylation age across mammalian tissues

https://www.biorxiv.....01.18.426733v1

 

Edited by albedo, 01 February 2021 - 12:41 PM.

[Harkijn]

Thanks for posting, Albedo. I hope readers here take some time to read up on this sensational development.  Josh Mitteldorf's blog will be helpful for informed laypersons (like me) to comprehend the importance of this step.

https://joshmitteldo...cienceblog.com/

[albedo]

Thanks for posting, Albedo. I hope readers here take some time to read up on this sensational development.  Josh Mitteldorf's blog will be helpful for informed laypersons (like me) to comprehend the importance of this step.

https://joshmitteldo...cienceblog.com/

 

Agree, Josh's blog is excellent and unless few exception people contributing there are often well informed scientists!
 

[Bryan_S]

OK we have another piece of the puzzle, CD1d and invariant natural killer T cells.

 

There are cell signaling influences that hamper any attempts at In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. This is why we have all watched for articles suggesting a drug pathway to help in the elimination for senescent cells. We term these small molecule drugs Senolytics. To date there have been many startup companies on this path but clinical trials have been met with scant results. Now we might actually be getting to the point of understanding the bodies own mechanisms involved in the elimination of Senescent cells.

 

Senescent cells: Senescent cells are end-of-life zombie cells that accumulate with age, and by the same token as we age our immune system also slows down, and the clearance and removal of these old worn-out zombie cells slowly halts. In essence, the combination of a slowing immune system causes an accumulation of Senescent cells as we age. These Senescent cells, in turn, contribute to many diseases associated with aging such as cancer, osteoarthritis, atherosclerosis, diabetes, and Alzheimer’s.

 

For the first time, researchers have identified the immune cells responsible for naturally clearing away these Senescent cells called invariant natural killer T cells, or iNKTs. Recently discovered Senescent cells on the other hand naturally alert the immune system to be removed by presenting antigen-presenting molecules on their cell surface called CD1d which no other cell in the body produces. The CD1d marker on the cell surface is the way the cell tells the immune system it's time to remove me.

 

In the 1990s a Japanese pharmaceutical research lab, looking for anticancer treatments stumbled on a marine sponge that produced ɑ-galactosylceramide. When tested scientists learned it attached to the antigen-presenting molecules in the Senescent cells and activated invariant natural killer T cells to clear away those cells.

 

The key thing about this recent development in understanding is many other techniques and drugs have been tried but there was a fundamental gap in our understanding as to why these old worn-out cells were accumulating with age. One group of drugs studied are called senolytics, which have worked with varying degrees of success in human clinical testing but have failed to make any real health difference to patients in these human clinical studies. So far to date, these drugs have been overall underwhelming. In fact, these drugs, in some cases, have killed healthy tissue. These drugs have taken a path to activate the innate self-destruct machinery already within a cell to eliminate them, but this was before we understood the body's natural T-cell method of Senescent cell removal when this internal machinery fails. Now we have a more complete picture.

 

That could give the iNKT approach a potential advantage over the senolytics drugs already in development.

 

https://medicalxpres...cent-cells.html

Scientists find mechanism that eliminates senescent cells

Scientists at UC San Francisco are learning how immune cells naturally clear the body of defunct—or senescent—cells that contribute to aging and many chronic diseases. Understanding this ...

medicalxpress.com

 

https://www.statnews...enescent-cells/

Reawakened immune cells attack cells tied to diseases of aging - STAT

Scientists have started to test whether natural killer, or NK, cells can be trained to go after hard-to-cure blood cancers in human patients. But making these sentinels of the innate immune system ...

www.statnews.com

 

[albedo]

Very encouraging, in mice:

 

A single short reprogramming early in life improves fitness and increases lifespan in old age

https://www.biorxiv.....05.13.443979v1

 

"Forced and maintained expression of four transcription factors OCT4, SOX2, KLF4 and c-MYC (OSKM), can reprogram somatic cells into induced Pluripotent Stem Cells (iPSCs) and a limited OSKM induction is able to rejuvenate the cell physiology without changing the cell identity. We therefore sought to determine if a burst of OSKM might improve tissue fitness and delay age-related pathologies in a whole animal. For this, we used a sensitive model of heterozygous premature aging mice carrying just one mutated Lamin A allele producing progerin. We briefly treated two months-young heterozygotes mice with OSKM and monitored their natural age-related deterioration by various health parameters. Surprisingly, a single two and a half weeks reprogramming was sufficient to improve body composition and functional capacities, over the entire lifespan. Mice treated early in life had improved tissue structures in bone, lung, spleen, kidney and skin, with an increased lifespan of 15%, associated to a differential DNA methylation signature. Altogether, our results indicate that a single short reprogramming early in life might initiate and propagate an epigenetically related rejuvenated cell physiology, to promote a healthy lifespan."

[TMNMK]

Couple things, I thought Bryan_S might be interested in this one that came across the wire recently (wrt EV's): 

 

Extracellular Vesicles and Hematopoietic Stem Cell Aging:

https://www.ahajourn...BAHA.120.314643

 

And on the main topic here, I think it's way to early to attempt to reprogram in-vivo in humans using small molecules (unless someone's circumstances are such that there's nothing to lose), but I would imagine that in the future it comes down to timing and dose (perhaps a bit like senolytics). That is to say, perhaps some combination of more easily obtainable chemicals and some pre- and post-DNA methylation age tests:

 

* valproic acid (https://resources.to...ter-v1-2019.pdf, https://www.scienced...590915003057), 

* β-hydroxybutyrate (https://www.cell.com...2765(18)30605-1),

* Forskolin (https://www.stemcell.../forskolin.html),

... what else I wonder?

 

There may come a day when we have enough evidence in animals that we're more clear on exactly what the dosage, timing, and cocktail ratios should look like, along with methods of administration but it does appear that chemically induced partial reprogramming could be feasible down the road. We just need a lot of experiments across a wide range of species, but I expect that'll be coming over the next 5 - 10 20 years (fudge for future pandemics & whatnot).

Edited by TMNMK, 07 June 2021 - 09:31 PM.

[Bryan_S]

<I think it's way to early to attempt to reprogram in-vivo in humans using small molecules>

 

Agreed this is all still too early. More research is needed.

 

Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging

 

Here is an example of how the embryo resets the clock in early development. Once this mechanism is understood and the function of those genes studied new approaches are likely to emerge.

 

https://advances.sci...t/7/26/eabg6082

 

Also see a simplified overview of the study: https://www.sciencen...ock-development

[albedo]

Thank you Bryan_S, I loved this last paper by Gladyshev's team. So I guess this is a proof-of-concept that aging is universal, epigenetically controlled, starts extremely early (I recollect (I hope correctly) you might find senescent cells already in the embryo), can be reset and reversed. Am I stretching too much the concept the paper conveys?

[Bryan_S]

you might find senescent cells already in the embryo), can be reset and reversed. Am I stretching too much the concept the paper conveys?

 

I think that's a stretch. I think the newly fertilized cell carries a combination of the man and woman's aged markers and this gets reset.

[albedo]

I think that's a stretch. I think the newly fertilized cell carries a combination of the man and woman's aged markers and this gets reset.

 

Why a stretch Bryan-S? Not only senescent cells do seem to appear at embryonic level but they look plastic and with differentiated signaling. I hope I do interpret correctly:

 

"... Given all this research, the last place you would expect to find senescent cells would be at the very start of life. But now three teams of scientists are reporting doing just that. For the first time, they have found senescent cells in embryos, and they have offered evidence that senescence is crucial to proper development..."

https://www.nytimes....the-embryo.html

"...Embryonic senescent cells have been reported to be non-proliferative and subjected to clearance from tissues after apoptosis at late embryonic stage.^8,9 However, the interpretation for clearance of senescent cells at late embryonic stage is based on the disappearance of Cdkn1a (P21) expression and senescence-associated beta-galactosidase (SAβ-Gal) activity,^8,9 two commonly used senescence markers in the field. Currently, there is no genetic fate mapping evidence for senescent cell fate in vivo. By lineage tracing of P21⁺ senescent cells, we found that embryonic senescent cells labeled at mid-embryonic stage gradually lost P21 expression and SAβ-Gal activity at late embryonic stage. Unexpectedly, some of the previously labeled senescent cells re-entered the cell cycle and proliferated in situ. Moreover, these previously labeled senescent cells were not cleared at late embryonic stage and remained in the tissue after birth. This study unravels in vivo senescent cell fates during embryogenesis, indicating their potential plasticity..."

https://www.nature.c...1422-018-0050-6

 

Edited by albedo, 12 July 2021 - 12:29 PM.

[Bryan_S]

Sorry I haven't been around lately. I'm in Florida and COVID is kicking our ass. Our TV station is watching employees drop like fly's. I'm healthy but I'm sick of hearing "My body, My Choice."

 

Embryonic senescent cells

 

OK, that makes sense from a perspective of remodeling. So we start with one cell which gets reset, wiping unwanted aged epigenetic markers from Mom and Dad. As we grow tissue that mass must be trimmed and sculpted for function. So some cells are destined to die, which are needed in the beginning, then programed to die. As we examine a hand, what mechanism takes place to carve out the fingers? How are certain cells told to sacrifice themselves? The hand looks like a mitten and the fingers are sculpted from that tissue mass. I'm sure this remodeling is present throughout the body where tissue is grown then trimmed back. I had no idea those cells might exhibit signs of senescence. The fact that; "Unexpectedly, some of the previously labeled senescent cells re-entered the cell cycle and proliferated in situ. Moreover, these previously labeled senescent cells were not cleared at late embryonic stage and remained in the tissue after birth." Nice find my friend, it broadens the total perspective where certain cells are marked for removal by expressing senescent markers.

 

Next topic, Muscle protein that makes vertebrates more fit linked to limited lifespan

by Johns Hopkins University School of Medicine

https://phys.org/new...ed-limited.html

 

Here is an example of something that helps us survive to a reproductive age but hurts us as we get older.

 

"a protein called CaMKII improves strength, endurance, muscle health and fitness in young animals."

 

"the gene for CaMKII also contributes to an evolutionary tradeoff: increased susceptibility to age-associated diseases, frailty and mortality."

 

"According to the study leaders, the evolutionary conservation of genes that enable the young to run faster and respond robustly to "fight or flight" responses makes sense: It helps them to catch prey or evade predators, thereby ensuring their reproductive success. However, some of these genes carry a steep price that animals need to pay when they grow older."

 

So would you choose to disable a gene that helps in fright of flight situations to live longer? It's my belief there will be more of these kinds of discoveries and these will all weigh into epigenetic reprograming strategies for aging as the landscape is illuminated through research.

Edited by Bryan_S, 04 August 2021 - 07:04 PM.

[albedo]

Sorry I haven't been around lately. I'm in Florida and COVID is kicking our ass. Our TV station is watching employees drop like fly's. I'm healthy but I'm sick of hearing "My body, My Choice."

 

Embryonic senescent cells

 

OK, that makes sense from a perspective of remodeling. So we start with one cell which gets reset, wiping unwanted aged epigenetic markers from Mom and Dad. As we grow tissue that mass must be trimmed and sculpted for function. So some cells are destined to die, which are needed in the beginning, then programed to die. As we examine a hand, what mechanism takes place to carve out the fingers? How are certain cells told to sacrifice themselves? The hand looks like a mitten and the fingers are sculpted from that tissue mass. I'm sure this remodeling is present throughout the body where tissue is grown then trimmed back. I had no idea those cells might exhibit signs of senescence. The fact that; "Unexpectedly, some of the previously labeled senescent cells re-entered the cell cycle and proliferated in situ. Moreover, these previously labeled senescent cells were not cleared at late embryonic stage and remained in the tissue after birth." Nice find my friend, it broadens the total perspective where certain cells are marked for removal by expressing senescent markers.

 

Next topic, Muscle protein that makes vertebrates more fit linked to limited lifespan

by Johns Hopkins University School of Medicine

https://phys.org/new...ed-limited.html

 

Here is an example of something that helps us survive to a reproductive age but hurts us as we get older.

 

"a protein called CaMKII improves strength, endurance, muscle health and fitness in young animals."

 

"the gene for CaMKII also contributes to an evolutionary tradeoff: increased susceptibility to age-associated diseases, frailty and mortality."

 

"According to the study leaders, the evolutionary conservation of genes that enable the young to run faster and respond robustly to "fight or flight" responses makes sense: It helps them to catch prey or evade predators, thereby ensuring their reproductive success. However, some of these genes carry a steep price that animals need to pay when they grow older."

 

So would you choose to disable a gene that helps in fright of flight situations to live longer? It's my belief there will be more of these kinds of discoveries and these will all weigh into epigenetic reprograming strategies for aging as the landscape is illuminated through research.

 

Same here (EU) as in FL. World is small place...

Interesting comment bridging possibly the two different theories: antagonist pleiotropy and epigenetic reprogramming?

[Bryan_S]

Same here (EU) as in FL. World is small place...

Interesting comment bridging possibly the two different theories: antagonist pleiotropy and epigenetic reprogramming?

 

Bridging, OK that fits, but our readers might not know what antagonist pleiotropy is, so maybe we should explain that. Antagonistic pleiotropy hypothesis - Wikipedia

 

Evolution over time picks the strategies that do best at ensuring the next generation. The fact that some of those strategies shorten longevity doesn't matter if the favored gene expression helps the next generation to reach maturity and reproduce.

 

In the case of epigenetic reprogramming, this may be one gene of many we "may" wish to "dampen." However, that choice "may" carry consequences in varied situations. At this point I'm not leaning one way or the other because there is much to consider.

 

Imagine standing on a street corner waiting for the traffic Walk indicator, the flashing hand tells you to walk and you proceed into the crosswalk. As you do, a distracted driver fails to break and stop and you catch this motion out of the corner of your eye. Normally, with a functioning CaMKII gene your body reacts with almost no thought hastening your step and you avoid contact with the distracted drivers car. But what would happen if we silenced the CaMKII gene? This illustrates the choice we'd be making. Some moments in life need heightened physical responsiveness and there would be a performance trade-offs in making the decision to silence CaMKII.

 

Article Open Access

Published: 26 May 2021

 

CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution

https://www.nature.c...467-021-23549-3

Edited by Bryan_S, 06 August 2021 - 06:32 PM.

[albedo]

Bridging, OK that fits, but our readers might not know what antagonist pleiotropy is ...

 

Maybe this work might shed more light on a possible "bridge", supporting your comment, IMHO:

 

"...We propose that the diverse observations related to aging can be largely harmonized through what we designate as the ‘somatic restriction theory of aging’. We suggest that during development, global programmed alterations in gene expression occur in many cells and tissues of the body. Salient examples of the above include those spanning the PT, EFT, NT and AT, though it is likely others exist as well. These global alterations result in a progressive restriction of the differentiated state of somatic cells that benefits the organism in the pre- and perireproductive period by reducing the risks of developmental plasticity and its associated oncogenesis [67] as predicted by Williams. In addition, we propose that the narrowing of facultative plasticity of the differentiated state of cells in somatic tissues leads to a progressive failure to regenerate tissues in response to damage with regeneration being replaced with interstitial fibrosis.We further postulate that the developmental loss of regenerative potential leads to a switch toward a program whereby DNA damage leads to senescence as opposed to apoptosis. In other words, if tissues can robustly regenerate, then the cells can undergo apoptosis when they experience significant DNA damage. However, if tissues have lost regenerative potential, then damaged cells are more likely to institute DNA checkpoint arrest and subsequent senescence instead of apoptosis as a means of maintaining tissue function. Last, with regard to molecular mechanisms, we suggest that somatic restriction is mediated epigenetically by an altered distribution of heterochromatin..."

 

West MD, Sternberg H, Labat I, et al. Toward a unified theory of aging and regeneration. Regenerative Medicine. 2019;14(9):867-886.

https://pubmed.ncbi....h.gov/31455183/
 

[Bryan_S]

Maybe this work might shed more light on a possible "bridge", supporting your comment, IMHO:

 

Yes, we are in agreement. I believe many supporting gene's also play a role in aging, I believe these genes were selected to insure reproduction.

 

"CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution"

https://www.nature.c...467-021-23549-3

 

This particular gene modification was selected for 675-650 million years ago.

 

[albedo]

"...In this review, we will evaluate the current status of cellular reprogramming in the application of rejuvenation. We will also contextualise the efficacy of cellular reprogramming within the growing field of epigenetic age prediction..."

Simpson, D.J., Olova, N.N. & Chandra, T. Cellular reprogramming and epigenetic rejuvenation. Clin Epigenet 13, 170 (2021). https://doi.org/10.1...148-021-01158-7

https://clinicalepig...-01158-7#citeas

[Bryan_S]

"...In this review, we will evaluate the current status of cellular reprogramming in the application of rejuvenation. We will also contextualise the efficacy of cellular reprogramming within the growing field of epigenetic age prediction..."

Simpson, D.J., Olova, N.N. & Chandra, T. Cellular reprogramming and epigenetic rejuvenation. Clin Epigenet 13, 170 (2021). https://doi.org/10.1...148-021-01158-7

https://clinicalepig...-01158-7#citeas

 

Nice overview of the current reprograming studies.

[Bryan_S]

Reprograming research continues. The Yamanaka factors are tested again on tissue repair.

 

Reprogramming heart muscle cells to repair damage from heart attacks

https://medicalxpress.com/news/2021-09-reprogramming-heart-muscle-cells.html

 

“After several years of effort, the researchers discovered a way to get adult cardiomyocytes to revert back to fetal-like cardiomyocytes by reprogramming them using the Yamanaka factors c-Myc, Klf4, Sox2 and Oct4. Their research showed that such factors express for cell renewal. The reprogramming also featured an on/off switch using the antibiotic doxycycline.

 

They found that under both scenarios, heart regeneration occurred along with heart function improvement. The researchers also tried giving similar test mice doxycycline six days after experiencing heart damage and found it had no impact. Thus, the window of repair is short. Further testing also showed that if doxycycline was administered for too long a period, cancerous tumors developed. Much more work is required to determine if a similar approach might work for humans, and if it can be done without increasing the risk of cancer.”

 

As I’ve written before the Yamanaka factors come with some risks and I believe its like using a sledgehammer to do the work of a chisel or scalpel. It works but has risks! To follow this path you’d have to program a single cell human embryo to respond to the antibiotic doxycycline the same way. Plus how do you deliver the Yamanaka factors to each cell in a normal adult that didn't have this tool installed in every cell? 

 

 

Here is some research that caught my eye involving Notch signaling which was believed to be shut off and unavailable in adulthood. These researchers activated this pathway with radiation. Maybe these epigenetic targets should be determined and the associated mRNA's needed to exploit the regenerative affects.

 

Radiation therapy reprograms heart muscle cells to younger state.

https://medicalxpress.com/news/2021-09-therapy-reprograms-heart-muscle-cells.html

 

 

Notch signaling articles

[albedo]

This might be interesting, in particular for Bryan (should he does not know already): he was the one teaching me/us about EV!

 

Friends and foes: Extracellular vesicles in aging and rejuvenation

https://doi.org/10.1096/fba.2021-00077

[Phoebus]

Thanks for posting, Albedo. I hope readers here take some time to read up on this sensational development.  Josh Mitteldorf's blog will be helpful for informed laypersons (like me) to comprehend the importance of this step.

https://joshmitteldo...cienceblog.com/

 

 

Josh has really lost the plot when it comes to Covid, my goodness. 

 

His post about "Statistical Fraud in the FDA Vaccine Approval Process" is full of nonsense including taking VAERS as fact and then claiming the vaccine is killing people left and right. It's just bad science sounds like a youtube conspiracy theorist run amok. 

 

Makes me reconsider his approach to anti aging. 

[Bryan_S]

This might be interesting, in particular for Bryan (should he does not know already): he was the one teaching me/us about EV!

 

Friends and foes: Extracellular vesicles in aging and rejuvenation

https://doi.org/10.1096/fba.2021-00077

 

 

Great find albedo, it's how the cell signaling is packaged and expressed. So if you want to send a reprograming message, mimic the EV's and with  in vivo cells you can write RNA's to tell those cells to make and package other EV's. "EVs can serve as both local and long-range transport and intertissue signaling mechanisms for mRNA, miRNA, protein, and lipids and are a major source for cell-free DNA and RNA in humans." I think this is an important therapeutic delivery topic.

 

If I had to pick one organ to regenerate with EV's it would be the thymus. There are a number of articles centering on just the thymus as a possible ani-aging path because it's what educates our immune system. The organ with age turns to fat and as it does we see increased susceptibility to infection, autoimmune disease, and cancer. See Transgenic exosomes for thymus regeneration There are two types of extracellular vesicles (EVs): the submicron-size microparticles and the nanometer-size exosomes.

 

 

Phoebus, I think Josh Mitteldorf's blog has lost focus as you mentioned but he's written a post on A New Approach to Methylation Clocks, just last month. I've got to believe Josh will begin shifting his focus back too aging.

[Harkijn]

Josh has really lost the plot when it comes to Covid, my goodness. 

 

His post about "Statistical Fraud in the FDA Vaccine Approval Process" is full of nonsense including taking VAERS as fact and then claiming the vaccine is killing people left and right. It's just bad science sounds like a youtube conspiracy theorist run amok. 

 

Makes me reconsider his approach to anti aging. 

You're slightly OT Phoebus, but I agree that some of Mitteldorf's latest posts are weird indeed. As for this particular subject however his summary seems to me to be informative.

[albedo]

...

 

If I had to pick one organ to regenerate with EV's it would be the thymus. There are a number of articles centering on just the thymus as a possible ani-aging path because it's what educates our immune system. The organ with age turns to fat and as it does we see increased susceptibility to infection, autoimmune disease, and cancer. See Transgenic exosomes for thymus regeneration There are two types of extracellular vesicles (EVs): the submicron-size microparticles and the nanometer-size exosomes.

...

 

I would do the same That is why I am excited by the work of Greg Fahy on the TRIIM trial. I recollect his encouraging results on the pilot trial which has been published and look forward to the larger trial in progress TRIIM-X

https://onlinelibrar...1111/acel.13028

https://clinicaltria...how/NCT04375657

[albedo]

Interesting this is coming out from Google's Calico: "Partial reprogramming restores youthful gene expression through transient identity suppression". Is it what there are now doing? I am sorry if you have already seen it but thought useful to log it here too.

 

[kurt9]

Interesting, yes. Because I thought Calico was going to be as useless as Larry Ellison's "anti-aging" research organization.