In the study of neurodegenerative diseases and brain aging, crucial roles are played by methods for obtaining and studying neurons that retain the age characteristics of original cells. Direct reprogramming of fibroblasts into neurons allows for preserving tissue age-related changes, which is important for accurately modeling Alzheimer's and Parkinson's diseases.
Direct reprogramming methods allow transforming adult fibroblasts into neurons without passing through a stem cell state. This approach ensures the preservation of genetic patient characteristics and their age-related changes. Significant works in this area were published by Yoo et al. (2011) and Vierbuchen et al. (2010).
Research shows that neurons derived from fibroblasts of different donor age groups significantly differ in levels of DNA oxidative damage and dendritic tree structure. Specifically, 'older' neurons have more pronounced DNA oxidative damage (0.40±0.04 rel. units) compared to 'younger' ones (0.194±0.001 rel. units). Visual analysis of cells shows that 'older' neurons exhibit a more developed dendritic tree with a greater number of branches and branching points.
The use of induced pluripotent stem cells (iPSC) also opens up new possibilities for modeling neurodegenerative diseases. Liang Zhu et al. (2019) showed that stress-induced aging in iPSC-derived NSC may imply the pathogenesis of Parkinson's disease. Elsa Vera et al. (2016) and Justine D. Miller et al. (2013) developed methods for modeling age-related phenotypes of neurons through manipulations with telomerase.
The combined use of direct cell reprogramming and iPSC technologies opens up new opportunities in creating patient-specific disease models and drug development. Scientists Natalia Arkadyevna Mikhailova, Mikhail Georgievich Khitin, and Ilya Borisovich Bezprzvany actively conduct research in this area.
Significant roles are also played by studies on the molecular mechanisms of tissue aging. Steve Horvath (2013) proposed a method for assessing biological age using epigenetic markers.
Thus, modern methods of direct reprogramming and iPSC allow more accurately modeling age-related changes in neurons and studying the pathogenesis of neurodegenerative diseases.