CN-121995049-A - Immunoglobulin-related methods for identifying, preventing and treating tissue aging

Abstract

The present invention provides a method for identifying the degree of aging of a subject or a tissue or organ thereof, comprising a) detecting the presence of immunoglobulin (Ig) molecules in a sample from said subject, and b) comparing the result of said detection with a reference value. The invention also provides methods of modulating aging in a subject or a tissue or organ or cell thereof by Ig, and methods of screening for anti-aging compounds or compositions by detecting Ig, or identifying the effect of a drug on aging.

Inventors

• LIU GUANGHUI
• ZUO YUECHENG
• ZHANG WEIQI
• QU JING
• MA SHUAI
• JI ZHEJUN
• GENG LINGLING
• CAI YUSHENG
• ZHANG BIN
• LI JIAMING

Assignees

• 中国科学院动物研究所

Dates

Publication Date

20260508

Application Date

20251031

Priority Date

20241101

Claims (20)

1. 1. A method for identifying the degree of aging of a subject or a tissue or organ thereof, comprising A) Detecting the presence of immunoglobulin (Ig) molecules in a sample from said subject, and B) Comparing the result of the detection with a reference value.
2. 2. The method of claim 1, wherein the reference value is obtained by detecting a reference object.
3. 3. The method of claim 1 or 2, wherein the reference value is obtained by detecting a reference subject population.
4. 4. The method of any of claims 1-3, wherein the presence of the Ig molecule comprises expression, concentration and/or distribution of the Ig molecule or heavy or light chain of the Ig molecule or fragment thereof, and number, proportion and/or distribution of Ig-positive cells.
5. 5. The method of claim 4, wherein the Ig molecule is selected from the group consisting of IgG, igM, and IgA.
6. 6. The method of claim 4, wherein the method comprises detecting the concentration or distribution of an immunoglobulin light chain constant region (Igkc).
7. 7. The method of any one of claims 1-6, wherein the sample is selected from the group consisting of heart, lung, lymph, spleen, gut, testis, spinal cord, and brain samples.
8. 8. The method of any one of claims 1-7, wherein the presence of the Ig molecule is detected by a protein binding molecule.
9. 9. The method of claim 8, wherein the protein binding molecule is selected from the group consisting of a receptor for an Ig molecule or a ligand binding portion thereof, such as pIgR, fcαri, fcγri (CD 64), fcγrii (CD 32), fcγriii (CD 16) or fcγriv, and an anti-Ig antibody or an antigen binding portion thereof and derivatives thereof.
10. 10. A method of preparing an animal model of aging comprising administering an Ig molecule to an animal or increasing the level of an Ig molecule in an animal.
11. 11. The method of claim 10, wherein the Ig molecule is selected from the group consisting of IgG, igM, and IgA.
12. 12. The method of claim 10 or 11, wherein the animal model is an animal model of aging of a tissue or organ, the method comprising topically administering the Ig molecule in the tissue or organ or increasing the level of Ig molecule in the tissue or organ.
13. 13. The method of claim 11, wherein the tissue or organ is selected from the group consisting of heart, lung, lymph, spleen, digestive tract, testis, spinal cord, and brain.
14. 14. A method of preparing a cell model of aging comprising contacting a cell with an Ig molecule.
15. 15. The method of claim 14, wherein the Ig molecule is selected from the group consisting of IgG, igM, and IgA.
16. 16. The method of claim 14 or 15, wherein the cell is an animal cell, such as a non-human mammalian cell, a non-human primate cell, or a human cell.
17. 17. A method of treating or preventing aging or an aging-related disorder in a subject in need thereof, comprising reducing the level of an Ig molecule or the level of an Ig receptor in the subject, e.g., the aging-related disorder is a chronic disorder, e.g., selected from the group consisting of arthritis, premature ovarian failure, liver fibrosis, lung fibrosis, debilitation, and cardiovascular disease.
18. 18. The method of claim 17, wherein the senescence is senescence of a tissue or organ, the method comprising reducing the level of an Ig molecule or the level of an Ig receptor in the tissue or organ.
19. 19. The method of claim 17 or 18, wherein the Ig molecule is selected from the group consisting of IgG, igM, and IgA.
20. 20. The method of any one of claims 17-19, wherein the Ig molecule is IgG.

Description

Immunoglobulin-related methods for identifying, preventing and treating tissue aging Technical Field The invention relates to the field of biological medicine. In particular, the invention provides methods for identifying and/or modulating aging. More particularly, the present invention relates to methods for identifying the extent of aging by detecting the presence of immunoglobulins in a tissue, or preventing, treating or delaying aging by reducing immunoglobulin levels. Background Organisms are highly ordered and complex systems consisting of billions of cells that communicate as functional units in organ structures, organ systems, and the whole body. In aging tissues, the integrity of the spatial structure is gradually eroded, resulting in a decline in system function, which is highly heterogeneous in organs and tissues. Studying these temporal and spatial multi-tissue cell changes helps identify previously unknown molecular mechanisms that drive senescence and understand how to slow down senescence in organisms for these mechanisms. Accumulation of senescent cells is causally related to morphological changes and functional decline in senescent tissue. Senescent cells release pro-inflammatory molecules, such as cytokines and chemokines, collectively known as the senescence-associated secretory phenotype (SASP), which can damage neighboring non-senescent cells and cause age-related diseases. However, the distribution and molecular characteristics of senescent cells within tissues are variable within and between organs. Thus, analysis of the location of senescent cells and their environment and their interaction with neighboring cells has significant potential to advance our understanding of the driving factors of senescence and may help identify potential targets for intervention. On the other hand, immune aging (Immunosenescence) is one of the important contributors to aging of the body, and refers to the phenomenon of gradual deterioration and decline or disorder of the immune system with age. Among them, immune aging affects the innate and adaptive immune functions of the human body, resulting in increased susceptibility of the elderly to infection, cancer and autoimmune diseases. While immunoglobulins, as a central tool of the immune system, play an important role in the recognition and neutralization of antigens (such as bacteria, viruses, toxins, etc.). With aging, the distribution of immunoglobulin in tissues, functional changes, and the influence on cell aging are also largely blank. Disclosure of Invention The inventors have unexpectedly found that immunoglobulins accumulate abnormally in aging tissues or organs and have the potential to drive cellular aging and inflammatory factor release. In a first aspect, the present invention provides a method of identifying the degree of aging of a subject or a tissue or organ thereof, comprising A) Detecting the presence of immunoglobulin (Ig) molecules in a sample from said subject, and B) Comparing the result of the detection with a reference value. In some embodiments, the reference value is obtained by detecting a reference object. In some embodiments, the reference value is obtained by detecting a population of reference subjects. In some embodiments, the presence of the Ig molecule includes expression, concentration, and/or distribution of the Ig molecule or heavy or light chain of the Ig molecule or fragment thereof, as well as the number, proportion, and/or distribution of Ig-positive cells. In some embodiments, the Ig molecule is selected from IgG, igM, and IgA. In some embodiments, the methods comprise detecting the expression, concentration, or distribution of immunoglobulin light chain constant regions (Igkc and/or Iglc). In some embodiments, the sample is selected from the group consisting of heart, lung, lymph, spleen, digestive tract, testis, spinal cord, and brain samples. In a second aspect, the invention provides a method of preparing an animal model of aging comprising administering an Ig molecule to an animal or increasing the level of an Ig molecule in an animal. In some embodiments, the Ig molecule is selected from IgG, igM, and IgA. In some embodiments, the animal model is an animal model of aging of a tissue or organ, the method comprising topically administering the Ig molecule in the tissue or organ or increasing the level of Ig molecule in the tissue or organ. In some embodiments, the tissue or organ is selected from the group consisting of heart, lung, lymph, spleen, digestive tract, testis, spinal cord, and brain. The invention also provides a method of preparing a cell model of aging comprising contacting a cell with an Ig molecule. In some embodiments, the Ig molecule is selected from IgG, igM, and IgA. In some embodiments, the cell is an animal cell, such as a non-human mammalian cell, a non-human primate cell, or a human cell. In a third aspect, the invention provides a method of treating or preventing aging and aging-rela