Systems biology research on young blood promoting the rejuvenation of the body’s multi-tissues. The figure is from the paper
Can young blood induce the regeneration of aging tissue? Can it promote the “rejuvenation” of aging organs?
On May 24, a study published in Cell-Stem Cells by the Institute of Zoology of the Chinese Academy of Sciences and the Beijing Institute of Genomics of the Chinese Academy of Sciences confirmed that the above ideas are not “nonsense” and others.
By constructing an allogeneic symbiosis model, the researchers made the blood of old mice and young mice “interchangeable”, and after 5 weeks, the aging markers of multiple tissues in older individuals were significantly reduced.
Paired in pairs, allogeneic symbiosis
For a group of mice that have reached the age of 2 (equivalent to 65-70 years old in humans), they must not have expected to “return to youth” in their lifetime.
Young and old mice were paired in pairs, and researchers constructed an allogeneic symbiosis model. In short, surgery involves connecting two animals of different ages and in different health states so that they share a common bloodstream. This is a model of a shared circulatory system first developed in 1864 by French zoologist Paul Bert to study exactly what substances in the blood affect health.
Once the allogeneic symbiosis model is established, the blood can penetrate each other.
Theoretically, the organs and tissues of the whole body can be affected by “allogeneic symbiosis”, but due to scientific focus, researchers mainly selected 7 kinds of tissues and organs such as brain, liver, skeletal muscle, skin, bone marrow, spleen and peripheral blood for in-depth analysis.
The elderly “return to youth”, the young “young and old”
Using single-cell transcriptome sequencing techniques, they revealed a panoramic variation in the cell “age” of old and young individuals caused by allogeneic symbiosis.
The study found that after blood exchange, the elderly mice showed typical “youthful” changes. It is mainly manifested in the improvement of the microenvironment of aging tissues and the activation of corresponding stem cells. That is to say, the young blood environment activates the aging, damaged, and exhausted stem cells in the bone marrow, skin and other tissues and organs of the elderly mice.
One of the most reactive cell types is hematopoietic stem cells in the bone marrow. Under the continuous “soaking” of young blood, the gene expression characteristics of old hematopoietic stem cells become closer to the youthful state.
On the other hand, when it comes to young mice, it is slightly bitter. Originally, it is the age of vigorous energy and unlimited vitality, but it presents a kind of “aging” that violates the norm: different organs, tissues and cell types show the characteristics of accelerated aging.
“Combining differential gene expression, core regulatory transcription factors, and cell-to-cell communication analysis, we found a series of hematopoietic stem cell senescence regulators represented by the epithemic regulatory gene YY1 and cell chemokine CCL3.” Ma Shuai, co-first author of the study and a researcher at the Institute of Zoology of the Chinese Academy of Sciences and the Beijing Institute of Stem Cell and Regenerative Medicine, told China Science Daily.
He said that it is precisely because of the discovery of these “anti-aging” genetic codes, if the future can be designed for these regulatory factors related intervention strategies, may help people delay aging, prevent the occurrence of diseases in old age. At the same time, this faces many challenges and problems.
Why is that? Are there differences between different tissues and organs?
In allogeneic symbiosis systems, cells that flow with blood exchange must also be mentioned. Just as a river is opened between two pieces of land and the seeds flow with it, cells between two individuals may exchange with each other to reach the various tissues and organs.
So, is it the improvement of the blood environment, or the arrival of young mouse cells that makes the old mice “young”?
Further questioning, after the improvement of the blood environment, the cells of the elderly mice themselves have become more vigorous because they have been nourished? Or did you see that the “foreign monk” made the cells of the old mice themselves feel “stressed” or “crisis”, and strive to be stronger? Or did the cells of the elderly mice themselves choose to “lie flat”, relying only on the external blood environment and foreign young cells to achieve the result of “rejuvenation” of tissues and organs?
These cell-to-cell interactions are complex and changeable, and must be explored through sophisticated experimental design and technical means.
“We used two different genotypes of CD45.1 and CD45.2 as markers to distinguish the cells of allogeneic symbiotic elderly and young mice, and not only analyzed the hematopoietic immune cells derived from individuals of different genotypes through flow cytometry technology, but also further constructed a single-cell transcriptome atlas of allogeneic symbiosis of MICE with different genotypes of CD45.” Wang Si, the co-first author of this article and a researcher at Xuanwu Hospital of Capital Medical University, said.
The results of the study showed that in the allogeneic symbiotic system, the degree of communication between peripheral blood and spleen cells was high; while the degree of interconnection of hematopoietic stem cells in bone marrow was very low, and less than 1% of hematopoietic stem cells in young individuals came from elderly individuals, and less than 5% of young sources in older individuals.
“This suggests that the bone marrow hematopoietic stem cells of old mice undergo an endogenous change after being affected by young blood.” “In addition, in addition, in addition to the hematopoietic immune system, the peripheral physical tissues of elderly individuals will also be ‘rejuvenated’ by young blood,” Ma Shuai said. ”
It is worth mentioning that the researchers also found that Gilz, a factor with anti-inflammatory activity, changes in expression in different tissue cells may be a key regulator of systemic aging and rejuvenation.
Blood transfusion ≠ blood transfusion, and “blood transfusion to continue life” is not advisable
“This study reveals the biological mechanism of aging from the perspective of systems biology, and also provides important data resources and clue ideas for establishing scientific evaluation methods for aging, finding intervention targets and intervention strategies for aging, and has broad application prospects in scientific prevention and control of population aging.” Professor Wang Yanjiang, director and professor of neurology at Daping Hospital (Army Special Medical Center) of the Third Military Medical University, said.
Professor Yue Rui, deputy dean and professor of the School of Life Sciences and Technology of Tongji University, said, “This study provides a valuable single-cell resource for in-depth understanding of the mechanisms of aging and rejuvenation in allogeneic symbiotic systems, and provides a series of potential new targets for intervention and delay of aging in the body.” ”
The authors note that “blood swapping” and “blood transfusion” in this study are two concepts, and there is no clear evidence that transfusion of young blood can prolong the lifespan of animals or people, which is also not advisable.
Even in allogeneic symbiosis experiments, this study only analyzed 7 tissues and organs in mice in depth, which is still far from the generally understood systemic test. From mice to humans, from molecular mechanisms to intervention development and clinical trials, there is still a long way to go. (Source: China Science Daily Liu Runan)
Related paper information:https://doi.org/10.1016/j.stem.2022.04.017
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