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Scientists discover a diffusion barrier in neural stem cells helping them to stay young

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Posted September 21, 2015

We all know that human brain does not respond well to aging. However, for the most part, our brain manages resist negative effects of aging. In order to keep our nervous system fresh and working properly, neural stem cells generate new neurons throughout life in the mammalian brain.

The stem cells asymmetrically segregate damaged proteins (red) between the mother and the daughter cells (on the left: DNA grey). Responsible for this is a diffusion barrier. The strength of the barrier weakens with advancing age. This leads to reduced asymmetry of damaged protein segregation (on the right). (Image: UZH)

The stem cells asymmetrically segregate damaged proteins (red) between the mother and the daughter cells (on the left: DNA grey). Responsible for this is a diffusion barrier. The strength of the barrier weakens with advancing age. This leads to reduced asymmetry of damaged protein segregation (on the right). (Image: UZH)

However, aging takes its toll on them too and with years counting the potential for regeneration in the brain dramatically declines. There is not much known to science about how aging effects neural stem cells, but now scientists at the University of Zurich identified a novel mechanism of how neural stem cells stay relatively free of aging-induced damage.

In short, this mechanism could be described as a diffusion barrier, which regulates the sorting of damaged proteins during cell division. Even before scientists knew cellular aging factors are asymmetrically distributed between the mother and the daughter cell when cells divide. It ensures that daughter cell has a normal lifespan, despite the age of the cell that was divided to make it.

Dividing neural stem cells (outlined with a white line) establish a diffusion barrier in the endoplasmic reticulum during cell division. This barrier participates in the asymmetric segregation of aging factors such as ubiquitinated, damaged proteins (red) during cell division (DNA (blue) of 2 daughter cells at the end of mitosis). The barrier ensures proper neural stem cell proliferation. (Image: UZH)

Dividing neural stem cells (outlined with a white line) establish a diffusion barrier in the endoplasmic reticulum during cell division. This barrier participates in the asymmetric segregation of aging factors such as ubiquitinated, damaged proteins (red) during cell division (DNA (blue) of 2 daughter cells at the end of mitosis). The barrier ensures proper neural stem cell proliferation. (Image: UZH)

This process allows for rejuvenation and makes for fresh, well-functioning cells. Now scientists know a diffusion barrier that restricts movement of molecules from one side to the other side of the cell during cell division is at least partially responsible for this asymmetrical distribution of aging factors.

Knowledge about uneven distribution of aging factors between mother and daughter cells as gained using yeast cells, which are surprisingly good models of brain cells. However, scientists showed that this process is present in the stem cells of the adult mouse brain as well.

Researchers argue that a diffusion barrier in the endoplasmic reticulum is responsible for this. Endoplasmic reticulum is a channel system within the cell that, besides its other important functions, is important for protein synthesis and transport. This barrier prevents damaged proteins in the stem cell to get into the daughter cell during the division. Scientists say that the asymmetry of aging factors between the mother and daughter cells appears to be much greater than they thought it is.

However, we know that stem cells still age, which interferes with their function of producing new neurons throughout the lifetime of the brain. If this diffusion barrier worked perfectly endlessly, stem cells would always remain fresh and young. Scientists found that the barrier weakens with advancing age. Scientists found that as cells get older this asymmetry of distribution of age factors is reduced protein segregation gets damaged.

Scientists say that it could be one of the mechanisms that reduce capabilities of aged bran to regenerate, since old stem cells that retain larger amounts of damaged proteins require more time to reach division. Sebastian Jessberger, leader of the research team, said: “This is an exciting new mechanism involved in stem cell division and aging. But as of now we are only just beginning to understand the molecular constituents and the true meaning of the barrier for stem cell division in the brain.”

Although knowing how aging affects neural stem cells is already very important knowledge, scientists are already planning next steps for this research. Now they are going to focus on one key question – is the barrier established in all somatic stem cells of the body.

The answer to this question may only be approached through extensive research, which inevitably will take a lot of time. However, all efforts put into this will help scientists to make steps towards the ultimate goal – to create new therapies, targeting age-dependent alterations of stem cell activity in human disease.

Source: UZH

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