Aging, immunity, lifestyle-related diseases

Elderly medical care (lifestyle-related diseases, autoimmune diseases, etc.)

Hematopoietic stem cells in bone marrow are educated in the thymus and supply T cells, which are responsible for the Physiology adaptive immune system, to the periphery. However, it has been discovered that in the periphery of elderly people over 60 years old, where the thymus is atrophied, Physiology T cells decrease and senescence-associated SA-TEM cells accumulate instead. These cells are characterized by expressing memory TEM cell markers and the immune checkpoint protein PD-1, which induces a decrease in Physiology immune function. Furthermore, unlike normal Physiology adaptive immune systems, SA-TEM cells produce a variety of inflammation-related factors as bad SASP in target organs, causing the microenvironment to become chronically inflammatory. These side effects induce the constituent cells of the target organ to "senescence". These senescent cells stop the cell cycle, overcome their Physiology lifespan, and function as SASP. In recent years, it has been proposed that the onset of lifestyle-related diseases in the elderly is caused by the "senescence-associated immune system," and research and development is being conducted on methods to remove related SA-TEM cells and senescent cells.
Our research team, HEPNO2, at Hyogo Medical University, has discovered that a particular subset of aged T cells is a new target cell for lifestyle-related diseases, and is conducting drug discovery research, including verifying their validity as a therapeutic target for autoimmune diseases.

SA: senescence-associated
TEM: T effector memory
SASP: senescence-associated secretory phenotype

The discovery that a certain subset of senescent T cells is a new target cell for lifestyle-related diseases

The disease model mouse discovered by these researchers has the characteristic of "repeatedly reproducing the onset of pathology in a short period of time," giving it great advantages as it can be applied to elucidating the mechanisms of human pathology, searching for drug discovery targets, and evaluating the validity of drug discovery targets and the effectiveness of treatments.

Currently, we are verifying the validity of the drug discovery targets discovered using our lifestyle-related disease model mice in vitro, in vivo, and clinical systems, and searching for therapeutic drugs for autoimmune diseases such as Sjögren's syndrome. Using this experience, we will assist in research into lifestyle-related diseases caused by aging-related factors.

We developed a program to comprehensively analyze the time-dependent changes in genetic information in the "systemic environment" and "local organs where pathology develops" in disease model animals, and to identify new candidate target molecules. This method is highly useful and can be applied to other disease model animals.

• April 2011 Domestic application number: "Patent application 2010-112556" (approved) Title: Screening method for substances with blood cell maturation promoting activity
• July 2012 International application number: "PCT/JP2011/061057" (approved) Title: Screening method for substances having blood cell maturation promoting activity

1. Immune Aging and How It Works for Inflammation and Fibrosis. Nishiura H, Imasaka M, Yamanegi K, Fujimoto J, Ohmuraya M. Front Physiol. 2022 Jan 4;12:795508.