Imagine trying to understand how a car engine works, but you can’t get your hands on an actual engine. That’s the challenge scientists face when studying age-associated neurodegenerative diseases (NDDs) because they can’t access viable human brain specimens. However, advancements in reprogramming technologies have provided a solution! Scientists can now create neurons from induced pluripotent stem cells (iPSCs) or directly from somatic cells (iNs), allowing them to generate better disease models and design new drugs. But here’s the catch: iPSC technology has a flaw. It resets the aging hallmarks of donor cells, which is not ideal for accurately modeling age-related diseases like NDDs. Luckily, there’s another method called direct neuronal reprogramming that bypasses this issue. It converts somatic cells into neurons without going through a pluripotent intermediary stage, preserving the aging and epigenetic signatures of the donor. This approach is advantageous for studying the impact of aging on neurodegeneration and understanding the underlying pathological mechanisms of NDDs. To delve deeper into the differences between iPSC and iN models and their effects on NDD phenotype, you should definitely check out the fascinating research in this article!
Many diseases of the central nervous system are age-associated and do not directly result from genetic mutations. These include late-onset neurodegenerative diseases (NDDs), which represent a challenge for biomedical research and drug development due to the impossibility to access to viable human brain specimens. Advancements in reprogramming technologies have allowed to obtain neurons from induced pluripotent stem cells (iPSCs) or directly from somatic cells (iNs), leading to the generation of better models to understand the molecular mechanisms and design of new drugs. Nevertheless, iPSC technology faces some limitations due to reprogramming-associated cellular rejuvenation which resets the aging hallmarks of donor cells. Given the prominent role of aging for the development and manifestation of late-onset NDDs, this suggests that this approach is not the most suitable to accurately model age-related diseases. Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows the possibility to generate patient-derived neurons that maintain aging and epigenetic signatures of the donor. This aspect may be advantageous for investigating the role of aging in neurodegeneration and for finely dissecting underlying pathological mechanisms. Here, we will compare iPSC and iN models as regards the aging status and explore how this difference is reported to affect the phenotype of NDD in vitro models.
Dr. David Lowemann, M.Sc, Ph.D., is a co-founder of the Institute for the Future of Human Potential, where he leads the charge in pioneering Self-Enhancement Science for the Success of Society. With a keen interest in exploring the untapped potential of the human mind, Dr. Lowemann has dedicated his career to pushing the boundaries of human capabilities and understanding.
Armed with a Master of Science degree and a Ph.D. in his field, Dr. Lowemann has consistently been at the forefront of research and innovation, delving into ways to optimize human performance, cognition, and overall well-being. His work at the Institute revolves around a profound commitment to harnessing cutting-edge science and technology to help individuals lead more fulfilling and intelligent lives.
Dr. Lowemann’s influence extends to the educational platform BetterSmarter.me, where he shares his insights, findings, and personal development strategies with a broader audience. His ongoing mission is shaping the way we perceive and leverage the vast capacities of the human mind, offering invaluable contributions to society’s overall success and collective well-being.