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Application of autophagy-deacetylase SIRT3 regulation axis in blood anti-aging

A technology of deacetylase and regulating axis, applied in the field of biomedicine, can solve problems such as adverse reactions of blood transfusion, toxic and side effects of pretreatment schemes, cell damage, etc., and achieve the effects of improving treatment effects, reducing potential risks, and delaying blood aging

Pending Publication Date: 2020-09-01
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] 1. There are risks in blood transfusion. Although the blood has undergone strict screening and inspection procedures, there is still the possibility of transfusion-transmitted diseases and other adverse reactions of blood transfusion;
[0007] 2. Since the storage of autologous hematopoietic stem cells is not yet popular, the use of allogeneic hematopoietic stem cell transplantation has the disadvantages of limited donor sources, toxic and side effects in the pretreatment program, and the problem of immune rejection, requiring long-term use of immunosuppressants , and prone to problems such as transplant complications
[0008] 3. Although chemotherapy has a good effect of killing leukemia cells, it also has great damage to normal human cells, and chemotherapy will cause problems such as cell drug resistance, leading to leukemia recurrence
[0009] 4. CAR-T immunotherapy has the risk of triggering a cytokine storm

Method used

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  • Application of autophagy-deacetylase SIRT3 regulation axis in blood anti-aging
  • Application of autophagy-deacetylase SIRT3 regulation axis in blood anti-aging
  • Application of autophagy-deacetylase SIRT3 regulation axis in blood anti-aging

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Experimental program
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Embodiment 1

[0070] First, the inventors of the present invention established a non-human animal model (Atg7 f / f ; vav-iCre), and the relationship between the loss of autophagy and the expression level of SIRT3 in non-human animal hematopoietic cells was studied.

[0071] see Figures 2a-2g as shown, Figure 2a means atg7 f / f ; Transcriptome sequencing volcano in vav-iCre hematopoietic stem progenitor cells; Figure 2b means atg7 f / f ;Expression of SIRT family in vav-iCre hematopoietic stem progenitor cells; Figure 2c Indicates Q-PCR detection of atg7 f / f ; SIRT family mRNA expression in vav-iCre hematopoietic stem progenitor cells; Figure 2d Indicates Q-PCR detection of atg7 f / f ; Pre-mRNA expression of SIRT in vav-iCre hematopoietic stem progenitor cells; Figure 2e Indicates streaming detection atg7 f / f ; The protein level of SIRT3 in vav-iCre hematopoietic cells at all levels; Figure 2f Indicates Western blot detection of atg7 f / f ; vav-iCre single core and Lin - SIRT3...

Embodiment 2

[0078] Since the above experimental results suggest that there is indeed an autophagy-steamylase SIRT3 regulatory axis in hematopoietic stem and progenitor cells, the inventors of the present invention have further investigated the effect of high-expression autophagy-steacetylase SIRT3 regulatory axis on human aging hematopoietic cells. The effect on the level of autophagy was studied.

[0079] see Figures 3a-3d as shown, Figure 3a Indicates the correlation between age and red blood cells, lymphocytes and hemoglobin in 4250 cases of human peripheral blood samples; Figure 3b Indicates the autophagy-related gene transcription level of human bone marrow hematopoietic stem cells; Figure 3c Indicates the autophagy level of hematopoietic cells downstream of human bone marrow; Figure 3d Indicates the autophagy level of human bone marrow hematopoietic stem cells.

[0080] From Figures 3a-3d It can be seen that in aged hematopoietic stem cells, the expression level of autoph...

Embodiment 3

[0088] Since the above experimental results suggest that the highly expressed autophagy-steamylation enzyme SIRT3 regulatory axis can rescue the decline in the level of autophagy in human aging hematopoietic stem cells, so the inventors of the present invention have asked whether it is possible to seek a new method in aging non-human cells with impaired autophagy function. The feasibility of highly expressing the autophagy-steamylase SIRT3 regulatory axis in human animal hematopoietic stem cells was studied in depth.

[0089] A method for highly expressing the autophagy-steamylase SIRT3 regulatory axis in aging non-human animal hematopoietic stem cells with impaired autophagy, comprising the following steps:

[0090] Step 1) Obtaining the full-length fragment of mouse SIRT3 gene by molecular cloning method, and inserting it into a lentiviral vector;

[0091] Step 2) Transfect 293T cells with the lentiviral vector inserted into the full-length fragment of the mouse SIRT3 gene a...

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Abstract

The invention discloses an application of an autophagy-deacetylase SIRT3 regulation axis in blood anti-aging. The regulation axis is expected to become a target for preventing or treating aging-related blood diseases, or is expected to be used for preparing a medicine for preventing or treating aging-related blood diseases, so that the defects and deficiencies of an existing treatment method are expected to be overcome, the treatment effect is improved, the pain of a patient is relieved, and the potential risk is reduced and the like. Meanwhile, the invention discloses a method for high-expression autophagy-deacetylase SIRT3 regulatory axis in senescent non-human animal hematopoietic stem cells with impaired autophagy function and application. The method is expected to be used for firstlyestablishing a high-expression autophagy-deacetylase SIRT3 regulatory axis hematopoietic stem cell model with a blood aging delaying effect, and then, moving back individuals to achieve an effect of rejuvenating the hematopoietic stem cells, so that the blood aging is delayed and great significance in preventing and treating hematological diseases related to aging is achieved.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to the application of the autophagy-deacetylase SIRT3 regulatory axis in blood anti-aging, and also relates to a high-expression autophagy-deacetylase SIRT3 in aging non-human animal hematopoietic stem cells with impaired autophagy function. Methods and applications of the acetylase SIRT3 regulatory axis. Background technique [0002] Relevant studies have shown that with age, the risk of blood diseases also increases. For example, elderly individuals are prone to anemia. According to statistics, about 17% of people over 65 years old suffer from anemia, and elderly individuals also have other underlying diseases, such as myelodysplastic syndrome. The important reason for these diseases is that the aging hematopoietic stem cells in the human body undergo clonal hematopoiesis. The hematopoietic stem cells undergoing clonal proliferation have abnormal downward differentiation ab...

Claims

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Application Information

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IPC IPC(8): C12N15/867C12N5/10A61K38/17A61P39/06
CPCC12N15/86C12N5/0647C12N9/80A61K38/1709A61P39/06C12N2510/00C12N2740/15043
Inventor 王建荣方艺璇
Owner SUZHOU UNIV
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