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Screening of chemical compounds that prevent senescence-associated T cells and their application to age-related diseases

Abstract

Our study aims to develop drugs to prevent or cure the disfunction of immune systems and chronic inflammation due to immunosenescence. Our immune system prevents us from infection by pathogens like viruses and bacteria. The age-related decline in immune function makes individuals vulnerable to these pathogens. In addition, dysregulation of immune systems induces chronic inflammation. It is also suggested that some age-related diseases involve immunosenescence.

Recent studies revealed that some atypical lymphocytes accumulate with age. For example, a population of specific helper T cells named senescence-associated T (SA-T) cells increases with age. Unlike normal helper T cells, which orchestrate immune systems in response to pathogens, SA-T cells do not respond to antigens; instead secrete pro-inflammatory factors, including osteopontin, resulting in the development of inflammatory symptoms. In this project, we are developing drugs to reduce the number and functions of SA-T cells to keep the immune status younger. For this purpose, we screen chemical compounds to find drug seeds that prevent SA-T cell formation or osteopontin secretion. We will then administer the hit compounds to aged mice to check they can reduce the SA-T cell population and restore immune functions.

We hope to develop promising drugs that prevent and cure age-related immune dysfunctions and diseases and help elderlies live healthily.

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Perspectives

  • Drugs that suppress SA-T cells can prevent and cure age-related diseases involving immune disorders.
  • Drugs that can keep the immune system younger can protect elderlies from infectious diseases.

Comments from principal researcher

The immune system plays an essential role in protecting us from infection. However, they sometimes worsen diseases and accelerate dysfunctions in aged individuals. I focused on SA-T cells, which are associated with inflammatory conditions. I am developing drugs to reduce their harmful influences. I hope the pharmaceuticals we create will keep our immune systems younger and support the healthy lives of aged people.