Vittorio Sebastiano from Turn.bio at ARDD2023: Cellular and Tissue Rejuvenation through Epigenetic..

[@emittfuller6348]

amazing and congratulations to Vittorio Sebastiano on being a part of the 2nd revolution of medicine

[@MrStarchild3001]

Vittorio Sebastiano from Turn Biotechnologies presented at the 10th Aging Research and Drug Discovery conference on cellular and tissue rejuvenation through epigenetic reprogramming. The key points from his presentation are: 1. Epigenetic drift, the progressive accumulation of epigenetic errors in the epigenome, is believed to be a fundamental driver of cellular aging and loss of function. Over time, genes that should be off get turned on and vice versa, impacting many hallmarks of aging. However, unlike the genetic code, the epigenome is reversible and can potentially be reset. 2. Inspiration for epigenetic reprogramming comes from the works of John Gurdon and Shinya Yamanaka showing that somatic cells can be reprogrammed into embryonic-like cells through somatic cell nuclear transfer (Gurdon) or induced pluripotent stem cell techniques (Yamanaka). This suggests aged cells could potentially be made more youthful. 3. In 2014, Sebastiano's group proposed using a controlled partial/transient reprogramming approach to change the age of cells without altering cell identity. They published foundational work on this "epigenetic reprogramming of aging" (ERA) in 2020 using a cocktail of 6 factors delivered as mRNAs. Since then, several studies have validated the approach in various tissues (muscle, skin, brain etc.) and organisms (mice, rats, primates). 4. Turn Biotechnologies is working to translate ERA into clinical applications by combining the biological concept, mRNA delivery vehicles, and lipid nanoparticle (LNP) delivery systems. Using mRNA avoids genomic integration risks and allows fine control of factor expression. Certain factors like MECP2 have beneficial effects when pulsed briefly in combination with others, contrary to some misconceptions. 5. In dermatology, ERA shows promising results: - In primary human fibroblasts, it causes transcriptomic resetting with activation of ECM related genes, anti-inflammatory effects etc. Fibroblast identity genes are appropriately modulated. - In human skin biopsies cultured ex vivo, aging biomarkers are favorably altered after ERA treatment. - An in vivo human skin xenograft model was developed to test ERA delivery and efficacy over several weeks. 6. For immunology, ERA is being explored to rejuvenate T cells: - Treated T cells from old donors proliferate robustly in response to tumor cells without any change in cell identity markers. - They express lower levels of exhaustion markers and maintain better anti-tumor cytotoxic function compared to controls. 7. ERA has potential applications in many tissues like muscle, eye, cartilage, blood, and skin, with dermatology and immunology being the initial focus areas. 8. Delivery of mRNA remains a key challenge, especially achieving sufficient penetration. For skin, microneedling/injections are the near-term approach, with topical solutions being developed. Broader interest and investment in mRNA and gene therapies, catalyzed by COVID vaccines, is expected to accelerate progress on novel delivery systems. In conclusion, Sebastiano presented compelling evidence for ERA as a promising approach to partially reverse cellular aging through transient epigenetic reprogramming. By translating ERA into viable clinical therapies, Turn Bio aims to ultimately increase human healthspan. While delivery hurdles remain, the underlying biology appears sound and reproducible across contexts. ERA represents an exciting frontier in the fight against aging and age-related dysfunction.

[@snorremortenkjeldsen6737]

Thank you for the great summary :)

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