RE: Epigenetische Reprogrammierung - 8

In Vivo Reprogramming Using Yamanaka Factors in the CNS: A Scoping Review
https://www.mdpi.com/2073-4409/13/4/343

Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice
https://www.liebertpub.com/doi/10.1089/cell.2023.0072

Zitat von Speedy im Beitrag #177

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Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice
https://www.liebertpub.com/doi/10.1089/cell.2023.0072

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Reprogramming: Rejuvenation Nature’s Way
https://medium.com/prime-movers-lab/repr...ay-75480454f735

Erklärt kurz die Grundlagen, zeigt den aktuellen Stand der Forschung, unterschiedliche Ansätze und mögliche Pitfalls.
Es wird in der Tat spannend sein zu erfahren, ob wir OSK(M) für alle Gewerbetypen werden nutzen können, oder ob es eine gewebespezifische Verjüngung ggf. auch mit unterschiedlichen Faktoren geben wird. Der Autor scheint eher auf Ersatzorgane zu spekulieren.

Ich glaube, nicht Organe sind die anzuzielende Lösung, sondern Stammzellen.

January // February 2024 Progress Update

Zitat

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At the close of 2023, we completed the experimental work for our partial reprogramming screen to date. In January, we received the resulting sequencing reads and were elated to find that it worked perfectly.

We’ve spent the past two months extracting insights from these data and preparing follow up experiments to test new reprogramming factor sets based on the results. In parallel, we’ve begun laying the groundwork for our Metabolism program by onboarding hepatocytes to the Discovery Engine.

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https://blog.newlimit.com/p/january-febr...progress-update

The long and winding road of reprogramming-induced rejuvenation
https://www.nature.com/articles/s41467-0...JPx2zpM0BpHppfA

Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche
https://www.nature.com/articles/s43587-0...DhNq82m5hKQiKDk

Tja, da können wir wohl noch mindestens 10-20 Jahre warten, bis es was brauchbares gibt. Vielleicht bedarf es sogar einer Reprogrammierung, welche auf den jeweiligen Gewebetyp bzw. das jeweilige Organ angepasst ist?

Comparative analysis of mouse strains for in vivo reprogramming

Zitat

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In vivo reprogramming through the forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) has demonstrated great potential for reversing age-associated phenotypes, as the combination of these transcription factors actively promote cell regeneration and rejuvenation in various tissues and organs. However, continuous in vivo OSKM expression raised safety concerns due to loss of cell identity, decrease in body weight, and premature death. Although cyclic short-term or targeted expression of the reprogramming factors can mitigate some of these detrimental effects in mice, systemic rejuvenation of wild type mice has remained elusive potentially due to these current technical limitations. To improve the fundamental understanding of in vivo reprogramming, we conducted a comparative analysis across multiple reprogrammable mouse strains, tissues, and expression methods, presenting a comprehensive atlas of formerly established strains. In addition, we developed novel reprogrammable mouse strains by avoiding OSKM expression in specific organs, in dividing cells, or implementing chimeric expression approaches within specific cells, thereby offering safer strategies to induce in vivo reprogramming and fully harness its potential. We hope that these new tools will become valuable resources for future research in this very exciting field of research with potential implications to human health.

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https://www.biorxiv.org/content/10.1101/...8.584074v1.full

Weiter:

Zitat

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As expected, liver and small intestine were the organs with the most significant increase in transcript levels of OSKM in 4Fj and 4Fk strains that show early mortality, followed by kidney (Figure 1D). However, in organs unrelated to doxycycline absorption, such as heart and skeletal muscle, OSKM transcript levels were more similar between the strains (Figure 1D). Similar results were obtained by qPCR (Figure S1B). In addition, 4Fk and 4Fj strains express higher levels of the reprogramming factors in average in all the tissues and organs analyzed (Figure 1E), correlating with their reduced survival.

Overall, these results suggest that OSKM expression is different across various reprogrammable mouse strains and higher in tissues and organs that are more exposed to doxycycline such as liver, intestine, and kidney, particularly in the 4Fj and 4Fk strains.

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Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation
https://elifesciences.org/articles/90579...rscM-dDz04aj0Lc

In vivo reprogramming of Caenorhabditis elegans leads to heterogeneous effects on lifespan
https://www.biorxiv.org/content/10.1101/2024.05.03.592330v1

Zitat von Speedy im Beitrag #186

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In vivo reprogramming of Caenorhabditis elegans leads to heterogeneous effects on lifespan
https://www.biorxiv.org/content/10.1101/2024.05.03.592330v1

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Zitat

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Similar to mice, expression of the reprogramming factors leads to premature death with different levels of toxicity at distinct developmental stages and aging.

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Damit könnte das Thema komplexer werden als erhofft.

Zitat von Prometheus im Beitrag #188

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Nun ja. Einerseits finde ich es wichtig, epigenetische Reprogrammierung nicht nur an der Maus zu etablieren, sondern auch an anderen Organismen. Andererseits denke ich, dass C. elegans hierfür kein geeigneter Modell-Organismus ist

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Lab-grown sperm and eggs: ‘epigenetic’ reset in human cells paves the way
https://www.nature.com/articles/d41586-024-01404-x

Könnte man sich damit etwa auch selbst resetten?

Die Frage ist ob man wieder zu Sperma werden will.
Was ist schlecht an der natürlichen Methode?
Sperma gibt's zur genüge und Eizellen auch.
Fortpflanzungsmedizin, wenn man die nicht gut findet ist man ja wahrscheinlich schon ein radikaler.

In vivo cyclic overexpression of Yamanaka factors restricted to neurons reverses age-associated phenotypes and enhances memory performance
https://www.nature.com/articles/s42003-024-06328-w

A Single-Short Partial Reprogramming of the Endothelial Cells decreases Blood Pressure via attenuation of EndMT in Hypertensive Mice

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OSK overexpression induced partial EC reprogramming in vitro, and these cells showed endothelial progenitor cell (EPC)-like features with lower migratory capability. OSK treatment of hypertensive BPH/2J mice normalized blood pressure and resistance arteries hypercontractility, via the attenuation of EndMT and elastin breaks. EGFP signal was detected in vivo in the prefrontal cortex of both BPN/3J and BPH/2J-treated mice, but OSK induced angiogenesis only in male BPN/3J mice. OSK-treated human ECs from hypertensive patients showed high eNOS activation and NO production, with low ROS formation. Single-cell RNA analysis showed that OSK alleviated EC senescence and EndMT, restoring their phenotypes in human ECs from hypertensive patients.

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https://www.biorxiv.org/content/10.1101/2024.05.20.595057v1

Unlocking cellular plasticity: Enhancing human iPSC reprogramming through bromodomain inhibition and extracellular matrix gene expression regulation
https://academic.oup.com/stmcls/advance-...586?login=false

Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy
https://link.springer.com/article/10.1007/s11357-024-01269-y

Zitat von Speedy im Beitrag #197

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Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy
https://link.springer.com/article/10.1007/s11357-024-01269-y

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Zitat

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In the context of the slight epigenetic rejuvenation observed in the treated old hippocampi, it is worth noting that only a small proportion of hippocampal cells would have been directly rejuvenated by our OSKM-GFP vector. Additionally, those few cells expressing the OSKM genes might have created a rejuvenating environment in the hippocampal tissue, contributing to a mild reduction in the epigenetic age of the whole region.

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Vielleicht deshalb die Ergebnisse, welche zwar eine deutliche Verbesserung gegenüber der Kontrollgruppe zeigen, aber z.B. beim Gedächtnis-Leistungstest immer noch meilenweit von denen junger Ratten entfernt sind?

Neuron-specific partial reprogramming in the dentate gyrus impacts mouse behavior and ameliorates age-related decline in memory and learning
https://www.biorxiv.org/content/10.1101/...ES-qBTwFmuo5wQQ

#10 The giant guide to partial reprogramming
https://peterottsjo.beehiiv.com/p/10-gia...l-reprogramming