Researchers identify neuroprotective mechanism against stem cell aging.


Neural stem cells generate new neurons throughout life in the mammalian brain. Neural stem cells are self-renewing, multipotent cells that generate the main phenotype of the nervous system. Stem cells are characterized by their capability to differentiate into multiple cell types via exogenous stimuli from their environment.  They undergo asymmetric cell division into two daughter cells, one non-specialized and one specialized. Neural stem cells primarily differentiate into neurons, astrocytes, and oligodendrocytes. However, with advancing age the potential for regeneration in the brain dramatically declines.

Now, a study from researchers at the University of Zurich has identified a novel mechanism of how neural stem cells stay relatively free of aging-induced damage.  This new discovery is a diffusion barrier which regulates the sorting of damaged proteins during cell division.  The study is published in the journal Science.

Previous studies show that with every division, cellular aging factors are asymmetrically distributed between the mother and the daughter cell allowing for rejuvenation and a full life span of the daughter independent of the age of the mother cell. At least partially responsible for this is the presence of a diffusion barrier that restricts movement of molecules from one side to the other side of the cell during cell division.

The current study showed that the stem cells of the adult mouse brain asymmetrically segregate aging factors between the mother and the daughter cells. Results show that a diffusion barrier in the endoplasmic reticulum, a channel system within the cell that is for example important for protein synthesis and transport, is responsible for this. The team observed that the barrier prevents retention of damaged proteins in the stem cell daughter cell keeping the stem cells relatively clean.  Thus, findings show that neural stem cell divisions appear to be much more asymmetric than previously anticipated.

Results show that the strength of the barrier weakens with advancing age which leads to reduced asymmetry of damaged protein segregation with increasing age of the stem cell. The lab hypothesize that this is one of the mechanisms responsible for the reduced regeneration capacity in the aged brain as stem cells that retain larger amounts of damaged proteins require longer for the next cell division.

The researchers surmise that this is an exciting new mechanism involved in stem cell division and aging, however, as of now they are only just beginning to understand the molecular constituents and the true meaning of the barrier for stem cell division in the brain.  For the future, the team state that one key question to be answered is whether the barrier is established in all somatic stem cells of the body. They go on to conclude that the answer to this question may open new routes to target age-dependent alterations of stem cell activity in human disease.

Source: University of Zurich

Dividing neural stem cells establish a diffusion barrier. It participates in the asymmetric segregation of aging factors such as ubiquitinated, damaged proteins (red) during cell division (DNA blue). The barrier ensures proper neural stem cell proliferation. Credit: UZH.

Dividing neural stem cells establish a diffusion barrier. It participates in the asymmetric segregation of aging factors such as ubiquitinated, damaged proteins (red) during cell division (DNA blue). The barrier ensures proper neural stem cell proliferation. Credit: UZH.

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