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Clearing Senescent Cells Prevents T1 Diabetes in Mice

Scientists have shown that the removal of non-dividing senescent cells, which are normally associated with aging, also appears to prevent Type 1 diabetes in diabetic mouse strains.

Clearing senescent beta cells prevents T1 diabetes

Type 1 diabetes (T1D) is a chronic condition in which the pancreas produces little or no insulin. Insulin is a hormone that allows sugar (glucose) to enter cells in order to create energy, so it is critical to cellular function and life.

T1D is an autoimmune disease, which means that the immune system, instead of protecting the body from invading pathogens, identifies a part of the body as a threat and attacks it. In T1D, the immune system targets the insulin-producing beta cells in the pancreas and destroys them.

In a new study, researchers demonstrate that senescent cells play a key role in the development of type 1 diabetes and that clearing them using senolytic therapy is sufficient to prevent diabetes in T1D diabetic mouse strains [1].

The research team used Bcl-2 inhibitors to block the survival pathways that senescent beta cells use to evade apoptosis, a built-in self-destruct system that destroys damaged cells. We have seen previous senolytic research that uses the drug navitoclax, which also blocks the Bcl-2 protein family [2]. Bcl-2 is also the target of the senolytic drug candidate UBX1967, which is being developed by UNITY Biotechnology to treat ophthalmologic diseases.

The end result here was that blocking Bcl-2 allowed the selective destruction of senescent beta cells, which, in turn, appeared to prevent T1D.

Summary

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by hyperglycemia due to progressive loss of pancreatic beta cells. Immune-mediated beta cell destruction drives the disease, but whether beta cells actively participate in the pathogenesis remains unclear. Here, we show that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP). Senescent beta cells upregulated pro-survival mediator Bcl-2, and treatment of NOD mice with Bcl-2 inhibitors selectively eliminated these cells without altering the abundance of the immune cell types involved in the disease. Significantly, elimination of senescent beta cells halted immune-mediated beta cell destruction and was sufficient to prevent diabetes. Our findings demonstrate that beta cell senescence is a significant component of the pathogenesis of T1D and indicate that clearance of senescent beta cells could be a new therapeutic approach for T1D.

Conclusion

The results of this new study are unusual given that type 1 diabetes is an autoimmune disease, not an age-related one, yet this data suggests that senescent cells play a role in its development. This previously unknown association has some interesting implications for autoimmune diseases. If the same association is found in human T1 diabetes, this opens the door for treating it with senolytic therapy in the same way.

The market for an effective T1 diabetes treatment is also considerably large, so it would not be a surprise to see senolytics being used in clinical trials for it in the near future.

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Literature

[1] Thompson, P. J., Shah, A., Ntranos, V., Van Gool, F., Atkinson, M., & Bhushan, A. (2019). Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes. Cell metabolism.

[2] Zhu, Y., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., … & Wren, J. D. (2016). Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors. Aging cell, 15(3), 428-435.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. jonrogerdespres
    March 9, 2019

    Never end this web site this is so good ! and thanks for writing it ! (this article)

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