Another mechanism of aging of blood stem cells
Researchers at the University of California at Berkeley, working under the guidance of Associate Professor Danica Chen, identified a new molecular mechanism critical for the aging process and demonstrated that manipulations of the process mediated by it contribute to the rejuvenation of blood cells. They found that the ability of blood stem cells (hematopoietic stem cells, HSCs) to repair damage caused by abnormal folding of protein molecules in mitochondria is a critical factor for their survival and regenerative capabilities.
The composition of mitochondria includes a huge number of proteins, the correct folding of molecules of which is a necessary condition for the normal functioning of these organelles, which are the energy centers of the cell. Violation of the folding process of protein molecules triggers the so–called response of unstructured proteins in mitochondria - a process that initiates the production of specific proteins that provide correction or elimination of abnormal molecules.
In the process of studying the proteins of the sirtuin family, the authors found that the mitochondrial response of unstructured proteins plays an important role in the aging of hematopoietic stem cells. Recently, these proteins have become increasingly well-known as regulators of the body's resistance to stress.
The researchers noticed that the levels of one of the sirtuins, namely SIRT7, increase in situations when cells have to cope with stress caused by the appearance of abnormally folded protein molecules in mitochondria. Moreover, it is known that the level of SIRT7 in the body decreases with aging.
The response of unstructured proteins has been studied very poorly, but the results of experiments on roundworms indicate an increase in its activity during periods of rapid growth of mitochondria.
Observation of adult stem cells has shown that they are usually at rest with minimal mitochondrial activity. These cells are activated only when tissue regeneration is necessary, which is accompanied by an increase in mitochondrial activity and subsequent proliferation and differentiation of stem cells. However, if errors occur in the folding of mitochondrial protein molecules, such rapid growth can cause serious harm to the body.
The authors isolated hematopoietic stem cells from the bone marrow of aging mice and demonstrated that increasing the level of SIRT7 in them reduces stress associated with improper folding of mitochondrial protein molecules. When administered back to animals, these cells demonstrated increased regenerative abilities.
A new study has shown that removing the SIRT7 protein from hematopoietic stem cells accelerates their proliferation. This acceleration is due to an increase in the intensity of protein synthesis and mitochondrial activity. Apparently, slowing down all these processes is a critical factor that gives stem cells the opportunity to recover from the effects of stress.
The authors compare the described mechanism with a traffic jam, which can be eliminated by removing the barrier that caused it, while its formation can be prevented by restricting the admission of cars to the motorway.
They believe that identifying the role of the described mitochondrial mechanism in the functioning of stem cells provides specialists with a new target for managing the aging process.
Article by M. Mohrin et al. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging published in the journal Science.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of California – Berkeley:
Even at a molecular level, taking it slow helps us cope with stress.
24.03.2015