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This article is reproduced from: Popular Science Cell Life)
The comparison of elderly somatic cells and young human cells found that there will be many more cells in the elderly that do not work but occupy a position, these cells are like zombies, not only do not work but also hinder the work of normal cells, such cells are what we often call senescent cells, also known as "zombie cells".
A major driver of aging is the accumulation of senescent cells. Abnormal aggregation of senescent cells can create an inflammatory microenvironment that leads to chronic tissue damage, further exacerbating the progression of many diseases, such as fibrosis of the liver and lungs, atherosclerosis, diabetes, and osteoarthritis. Therefore, eliminating senescent cells in damaged tissues can improve these pathological symptoms and even delay aging and prolong life.
On May 10, 2021, the University of California, San Francisco (UCSF) published a research paper in Med magazine titled "Invariant natural killer T cells coordinate removal of senescent cells." The researchers discovered a naturally occurring anti-aging mechanism in the human body: iNKT immune cells (i.e., constant natural killer T cells) can eliminate foreign body cells in the body, including senescent cells that accumulate DNA damage. However, as we age and other factors, such as obesity, iNKT cells become less and less active, and then chronic diseases emerge.
01.
Med: iNKT cell therapy removes senescent cells and prolongs lifespan
The researchers found that iNKT cells have unique receptors (not other cells in the human body), so they can activate iNKT cells without activating other types of immune cells. Moreover, they operate in a natural negative feedback loop, meaning that after a period of activity, they actively return to sleep, avoiding overtreatment.
△ Illustration of this study
So researchers at the University of California, San Francisco set out to find a way to activate iNKT cells, thereby eliminating senescent cells in humans.
The comparison of elderly somatic cells and young human cells found that there will be many more cells in the elderly that do not work but occupy a position, these cells are like zombies, not only do not work but also hinder the work of normal cells, such cells are what we often call senescent cells, also known as "zombie cells".
In the study, the researchers used a lipid-based molecule to activate iNKT cells and then removed senescent cells from diet-induced obese mouse models with pulmonary fibrosis mice.
The experimental results showed that after receiving treatment in both groups of mice, the number of senescent cells decreased compared with the control group. Among them, the blood glucose level of obese mice was improved. In addition, the damaged cells of pulmonary fibrosis mice decreased and their lifespan became longer.
△ Activation of iNKT cells clears senescent cells
One of the paper's authors, Professor Mallar Bhattacharya of UCSF, said the results of the iNKT cell study conducted in a mouse model of lung fibrosis offered hope for treatment of this potentially fatal disease, which often leads to patients needing lung transplants. "I think this is a potential immunotherapy for aging and fibrosis, and it's quite well tolerated." Next, we only need to determine the dosage to be administered and conduct clinical trials. ”
Corresponding author of the paper, Professor Anil Bhushan of UCSF, said that because senescent cells tend to accumulate in many tissues and are associated with many chronic diseases, he speculates that activating iNKT cells can be used to treat a wide variety of chronic diseases.
02.
Nature: CAR-T cell therapy reverses aging
With the increase of human average life expectancy, cardiovascular diseases, cancers and neurodegenerative diseases that come with aging will increasingly affect the quality of life of the elderly, so scientists have studied various means to "fight aging".
On June 17, 2020, a study on the treatment of aging was published in the top journal Nature, entitled "Senolytic CAR T cells reverse senescence-associated pathologies". The study found that age-related diseases could be treated using CAR-T cell therapies that target "senescent" cells. In mouse models of liver and lung cancer, the team found that the CAR-T therapy successfully cleared precancerous senescent cells, and the treatment significantly prolonged the survival of lung cancer mice.
CAR-T therapy is a breakthrough cancer treatment method at present, through gene editing technology to install a CAR with localization function on T cells (tumor chimeric antigen receptor), you can achieve the purpose of identifying tumor cells, inducing immune response, and efficiently killing tumor cells. The emergence of this treatment also provides researchers with new ideas in the study of anti-aging agents. If CAR-T cells can recognize senescent cells, they can transform anti-tumor therapies into anti-aging therapies.
The first step in developing to identify senescent cells should be to determine the surface characteristics of senescent cells. By analyzing three separate datasets of RNA sequencing constructed from aging models, the researchers finally identified the urokinase-type plasminogen agonist receptor (uPAR) as the "identity card" for senescent cells.
Aging often leads to a range of chronic diseases, such as liver fibrosis. Therefore, the researchers used induced mouse liver fibrosis as a model of liver fibrosis to conduct dose studies of CRA-T cells. Experimental results show that CAR-T cells can effectively eliminate senescent cells, reduce fibrosis and improve liver function.
Of course, judging from other studies that have been done so far, stem cells also play an important role in delaying aging.
By clearing these senescent cells can make room for the newborn cells, while the stem cells can be replenished, by homing to the place of tissue damage and differentiating into new functional cells, thus better fighting aging.
In the future, immune cell technology and stem cell technology may be able to work together on the road to fight aging, thereby helping people better extend their lives. Especially with the further deepening of the aging of the mainland population. A few days ago, the data of the seventh national census showed that the population of the mainland aged 60 and above was 264.02 million, accounting for 18.70%. Cell technology in the field of anti-aging in the future will have broad application prospects, so that people live longer and healthier!
Resources:
[1] Arora, et al., (2021). Invariant natural killer T cells coordinate removal of senescent cells. Med,
https://doi.org/10.1016/j.medj.2021.04.014
[2] Amor, C., et al., Senolytic CAR T cells reverse senescence-associated pathologies. Nature, 2020.
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