Receiving a vaccine to remove senescent cells and prolong lifespan?

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Nature Aging: Receiving a vaccine to remove senescent cells and prolong lifespan?

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Receiving a vaccine to remove senescent cells and prolong lifespan?

Nature Aging: Is the anti-aging vaccine here? Get a shot to remove senescent cells and prolong lifespan. 

Aging is a natural process. With age, all people will gradually age, which seems to be a natural law that cannot be changed.

However, in recent years, with the acceleration of global aging, countries around the world have set off a wave of anti-aging research, and various anti-aging drugs and therapies have also been discovered, such as nicotinamide , metformin and Senolytics therapy.

Previous studies have shown that the aging process of life is partly due to the development of senescent cells.

These senescent cells have been unable to function but have not died naturally.

At this time, these senescent cells will continue to produce many pro-inflammatory and tissue remodeling molecules to be poisoned. Other cells around.

Moreover, the scientists found that by transcriptome analysis, and cancer cells, like bad old cells will increase the expression “pro-survival network” to help them resist apoptosis or programmed cell death.

In 2015, Dr. James Kirkland of the Mayo Medical Center in the United States and others published a paper [1] in the journal Aging Cell , reporting a combination of drugs that selectively kill senescent cells – Senolytics . Senolytics therapy consisting of dasatinib and quercetin can selectively induce the death of senescent cells.

Among them, dasatinib can eliminate aging human adipocyte progenitor cells, while quercetin can kill aging human endothelial cells and mouse bone marrow stem cells, and the combination of the two has a stronger effect.

Since then, many animal studies have shown that Senolytic therapy can improve aging and prolong life.

Recently, researchers from Juntendo University in Japan published a research paper in Nature Aging,  entitled: Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. 

The study identified a target of Senolytic therapy- glycoprotein non-metastatic melanoma protein B ( GPNMB ) .

GPNMB shows enrichment in senescent cells.

Develop antibodies against GPNMB and use it as a vaccine to improve the symptoms of aging in mice and extend the lifespan of mice, especially male mice.

Senolytic this selective removal of senescent cells can improve the normal and case changes related to aging in mice.

However, most drugs that remove senescent cells inhibit the anti-apoptotic pathway, which may increase off-target effects on normal tissues.

Therefore, it is necessary to determine the specific target of Senolytic therapy.

In this latest study, the research team identified glycoprotein non-metastatic melanoma protein B (GPNMB) as the molecular target of Senolytic therapy.

GPNMB is a transmembrane protein. Analysis of the transcriptome data of senescent vascular endothelial cells shows that GPNMB is enriched on the surface of senescent cells .

GPNMB is also up-regulated in the vascular endothelial cells and/or leukocytes of human patients and mice with atherosclerosis.

As early as May 6, 2019, Wuhan University Song Baoliang team, Shanghai University of Science and Technology Qi Wei team in Nature Metabolism journal published a report entitled: GPNMB secreted from liver promotes lipogenesis in White adipose Tissue and aggravates Obesity and insulin resistance research papers 【3】. Details: Song Baoliang of Wuhan University and others discovered new therapeutic targets for metabolic disorders such as obesity and diabetes

This study shows that GPNMB is an important regulator of adipogenesis. GPNMB increases fatty acid synthesis in white adipose tissue and exacerbates diet-induced obesity and insulin resistance. Blocking GPNMB with neutralizing antibodies can improve diet-induced obesity and insulin sensitivity. Therefore, inhibiting GPNMB is a potential treatment for obesity and diabetes .

And this new study by Nature Aging confirms that knocking out GPNMB can reduce metabolic abnormalities and atherosclerosis in mice on a high-fat diet , and improve the state of aging.

Then, the research team developed an antibody that targets the GPNMB protein and used it as a vaccine.

After injection, the antibodies produced by the vaccine only bind to the GPNMB protein on the surface of senescent cells , thereby marking senescent cells and inducing antibody-dependent cell-mediated cytotoxicity (ADCC) to kill these senescent cells.

Next, the research team validated the vaccine in a mouse model of atherosclerosis (a disease caused by the accumulation of senescent cells) and aging mice.

Experimental results show that the vaccine can reduce the number of senescent cells in sclerosed arteries, reduce the weakness of aging mice and other aging-related symptoms.

In addition, this Senolytic vaccine can extend the lifespan of mice (on average by 20%) , especially the lifespan of male mice .

This indicates that this Senolytic vaccine against aging antigens can be used as a new Senolytic therapy.

Paper link:
1.https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12344
2. http s://www.nature.com/articles/s43 587-021-00151-2
3. HTTPS: //www.nature .com / Articles / s42255-019-0065-4

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