Harnessing Cell Reprogramming to Restore More Youthful Gene Expression: Yuri Deigin at EARD 2023

Summary

In this informative talk, Yuri Deigin introduces the concept of partial reprogramming, a promising approach to address aging by rejuvenating cells at the epigenetic level. He discusses the potential of gene therapies to reverse cellular hallmarks of aging, drawing on observations from nature that demonstrate aging's malleability across different species. Deigin highlights the role of epigenetics in aging, citing examples from social insects and mammals that exhibit lifespan variations controlled by epigenetic mechanisms. He further explores the safety and efficacy of partial reprogramming in vivo, as shown in studies that have successfully extended lifespan and improved healthspan in mice. The talk concludes with future directions for research, including tissue-specific therapies and the development of targeted gene delivery methods, offering a glimpse into the potential of partial reprogramming to transform human health and longevity.

Takeaways

• 🧬 Yuri Deynahan from Youth Bio is leading the development of gene therapies based on partial reprogramming to address the issue of aging, aiming to slow it down or even reverse it.
• 📈 Aging is a complex process with no consensus definition, but it involves cellular damage accumulation and various manifestations of aging which can be reversed at the cellular level through reprogramming.
• 🌐 The diversity of aging across different species indicates that aging is malleable and under genetic and epigenetic control, suggesting it's not governed by a universal physical law like the second law of thermodynamics.
• 🐝 Observations from nature, such as the honeybee and the black garden ant, show significant differences in lifespans despite sharing identical DNA, highlighting the role of epigenetics in aging.
• 🦋 The monarch butterfly and the Indian jumping ant are examples of epigenetic control of lifespan within a single species, demonstrating the potential for lifespan extension through epigenetic reprogramming.
• 🧬 Epigenetics refers to the control of gene expression, which varies not only between different cell types but also changes with time, including in response to aging.
• 🔄 Rejuvenation of cells is possible, as evidenced by the resetting of aging hallmarks during reproduction in various species, including humans.
• 🧪 The process of cellular reprogramming was first shown to be possible in 1962 by John Gurdon, and it was further proven that cells can be reprogrammed back to an embryonic-like state in 2006.
• 🐭 Partial reprogramming in vivo has been shown to rejuvenate cells and extend lifespan in mice, with one study demonstrating a 50% increase in lifespan in a fast-aging mouse model.
• 🛠️ While the exact mechanisms of how partial reprogramming leads to rejuvenation are not fully understood, hypotheses suggest it may relate to the early embryonic processes triggered by reprogramming factors.
• 💡 The transcriptomic and physiological rejuvenation induced by partial reprogramming has been observed in various studies, indicating a shift towards a more youthful gene expression pattern and improved cellular function.

Q & A

What is the main topic of discussion in the provided transcript?

The main topic of discussion is partial reprogramming, its potential in addressing aging, and the various aspects of aging that can be manipulated through this process.

What is the goal of partial reprogramming in the context of aging?

The goal of partial reprogramming in the context of aging is to slow down, and ideally reverse, the aging process by rejuvenating cells on a cellular level.

What is the significance of the variation in lifespans among different species as mentioned in the transcript?

The variation in lifespans among different species signifies that aging is malleable and can be influenced by genetic and epigenetic factors, which is important for understanding how aging can potentially be manipulated.

What is epigenetics and why is it relevant to aging?

Epigenetics is the control of gene expression, which determines which genes are expressed and when. It is relevant to aging because it controls the aging process and can be manipulated to potentially extend lifespan and rejuvenate cells.

How does the transcript suggest that aging is not a universal biological law?

The transcript suggests that aging is not a universal biological law because it highlights the diversity of aging patterns and lifespans in nature, indicating that aging can be influenced by biological factors rather than being a fixed law.

What is the role of epigenetic reprogramming in social insects as mentioned in the transcript?

In social insects, such as honey bees and ants, epigenetic reprogramming allows for different roles within the colony to have vastly different lifespans, demonstrating that epigenetics can play a significant role in determining aging and lifespan.

What is the significance of the observation that epigenetic clocks are synchronized across different tissues?

The synchronization of epigenetic clocks across different tissues indicates that aging is an epigenetically controlled process and that manipulating epigenetics could potentially influence the aging process across the entire organism.

What is the concept of 'rejuvenation' in the context of the transcript?

In the context of the transcript, 'rejuvenation' refers to the process of restoring cells or organisms to a more youthful state, which can be observed during reproduction and is a potential goal of partial reprogramming therapies.

What is the historical significance of the experiments by John Gurdon and the creation of Dolly the sheep in relation to cellular reprogramming?

The experiments by John Gurdon and the creation of Dolly the sheep were significant because they provided evidence that the DNA of differentiated cells still contains all the information necessary to create a complete organism, refuting the idea that cell fate is irreversible.

What are the potential therapeutic benefits of partial reprogramming as discussed in the transcript?

The potential therapeutic benefits of partial reprogramming include rejuvenating cells, extending lifespan, improving tissue health, and potentially treating or preventing age-related diseases.

What is the current status of human trials for partial reprogramming therapies?

As of the information in the transcript, there are no human trials underway for partial reprogramming therapies, but some companies are close to initiating clinical trials for specific indications.

What are the future directions for partial reprogramming research as mentioned in the transcript?

The future directions for partial reprogramming research include studying tissue-specific approaches, finding tailored factors for particular cell types, and developing targeted delivery vehicles for specific organs or tissues.