• The research has been published in the prestigious magazine Science.
  • Aging is a strategic line of study at the IIS Biodonostia.

Neural stem cells (NSC) continue throughout life to generate new neurons in different areas of the brain, such as the hippocampal dentate gyrus. This process is known as ‘neurogenesis’.

Adult neurogenesis provides a substantial lifelong exchange of hippocampal neurons, which are involved in certain kinds of learning dependent upon the hippocampus and the memory. Furthermore, the lack or alteration of neurogenesis is associated to neuropsychiatric diseases such as depression and epilepsy. The number of neurons generated is dynamically regulated. Thus, at an advanced age, there is a decrease in both the proliferation of neural stem cells and in neurogenesis, suggesting that the auto-renovating capacity of neural stem cells to generate progeny reduces in aged neuron stem cells. However, the cellular mechanisms that control the long term auto-renovation of hippocampal NSCs and that are involved in mediating the decrease associated to the age of their neurogenic potential remain unknown.

The study headed by researcher Sebastian Jessberger (Zurich University) with the participation of Marcos Araúzo, Ikerbasque Research Professor at the IIS Biodonostia (and head of the Computational Biology and Systems Biomedicine research group at the Biodonostia Health Research Institute) found that, during the cellular division of neural stem cells, a lateral diffusion barrier is generated in the endoplasmic reticulum membrane which promotes the asymmetric segregation of cellular components. They have shown that the strength of the said barrier weakens with age in response to deterioration of the components of the nuclear envelope associated to the Lamin protein. Said weakening prevents the asymmetric segregation of proteins damaged during cellular aging, thereby constituting one of the molecular causes of neuronal aging. These findings open the door to the existence of common mechanisms in the development of neurodegenerative diseases.

In the neural stem cells of young brains, the damaged proteins are asymmetrically inherited, so that the non-‘mother’ cell inherits damaged proteins while the ‘mother’ daughter cell escapes such proteins. While, surprisingly, in the neural stem cells of aged brains the damaged proteins are distributed more symmetrically between the new ‘mother’ daughter cell and the non-‘mother’ cell.

This finding, in addition to being one of the reasons that explains neuronal aging, may contribute to better understanding of different neurodegenerative diseases, given that it opens the door to the existence of common causes in different ailments. It may also help to understand the aging of other kinds of cells in the organism.