Stem cells control and reverse aging in mice

Chronic stress can lead to neuronal loss of control over gene expression. A group of scientists led by Claus C. Lambesis, PhD, of West Germany’s Biozentrum, and at the University of Freiburg (Germany), have shown that both cell signaling pathways and complement pathways determine cell fate when stressed. The findings were published on May 15 in eLife.

Cell signaling appears to play an important role in physical equilibrium in the body. Cell division can be stopped, even substantially, by activating signaling in the nucleus. This happens partially or completely by means of induced pluripotent stem cells (iPSCs) – in which all genetic information of the donor recipient cell is transformed into a second line of cells, which thus nourish the recipient. SPCs are thus a promising source of cells for future regenerative therapies for specific organs such as bone, cartilage, heart, and kidneys. Unfortunately, in the course of biological activity they also tend to generate specialized immune cells. In particular, their stem function is important to the propagation of pluripotent stem cells. And abnormalities of their proliferation can also be associated with numerous diseases associated with cell stress and stem function.

Stem-cell-driven immune regulation.

Chronic stress can result in the progressive activation of stem cells (mitotic/proliferative dysregulation), leading to neuronal loss of control over gene expression. Here, the signal pathway is regulated by Neurexin B (Nef), a protein expressed predominantly in astrocytes (central nervous system). In experiments using a mouse model, the scientists showed that Nef activation impairs myelination and thus affects neural structure and function. They also showed that adipocytes – cells that are lacking in PV1 cells – become the main source of Neurexin B signaling as well. These two results indicate that the adaptive vascular defenses activated in response to chronic stress are not only strengthened but also reverses these neural deficits.

“These findings show that systemic NEURXIN B signaling facilitates and strengthens the acquired effects, as is shown in vivo by our experiments”, says Claus C. Lambesis, Professor for Regenerative and Epigenetic Medicine at the University of Freiburg and the coordinating center of the CCRE mission.

Optimal activation of the complement system.

Lambesis’ group has a long history of studying complement regulatory pathways, in particular with regard to the transcription factors WRIMA and WAIT1 as potential targets for modulating complement signaling. For this study, the scientists activated the organization of complement signaling either in the DG as well as the cortex or in the periphery via fluorescent TRPV4 sensors. Comprehending the ROS- and NOXP-independent effects of CBF intake has therefore proven an important challenge. In the present study, the scientists first opened a STRIP-operated cell valve, thus enabling them to overcome NOXP-induced impairments.