Our living organisms undergo aging processes, accumulating senescent cells – cells that cease dividing but maintain metabolic activity and are not destroyed by complex stresses within and outside the cell, such as telomere shortening, oxidative stress, tumor-inducing stress, and tissue injury. Senescent cells are well-known for preventing the proliferation of damaged cells, thereby inhibiting early-stage cancer. However, the accumulated senescent cells gradually secrete Senescence-Associated Secretory Phenotypes (SASPs), including inflammatory factors, growth factors, and proteolytic enzymes. These factors ultimately induce a cell non-autonomous chronic inflammatory response in the environment within the tissues. Furthermore, they lead to cellular and functional impairments in surrounding cells and tissues, increasing the likelihood of various age-related chronic diseases.

 

To target these senescent cells and treat age-related diseases, current research is actively underway to develop drugs that regulate the anti-apoptotic pathways (Bcl-2/Bcl-XL family and the dependence receptor PI3K/AKT, Ephrines) specifically overexpressed in senescent cells. Our team has discovered drugs (senolytics) that eliminate senescent cells by regulating the MDM2-p53 interaction and has developed a novel treatment technique for osteoarthritis using this approach. Although these drugs targeting senescent cells have shown promise in animal studies for treating age-related diseases, they currently do not act on all types of senescent cells and diseases, as cellular senescence can occur through various mechanisms, leading to increased diversity among cells and tissues. To overcome this challenge, our aging research and technology lab is conducting studies related to 1) identifying novel markers for cellular senescence processes in various cells/tissues and 2) developing methods using both biological and engineering approaches, aiming to extend the health span of individuals and prevent and develop therapeutic drugs for age-related diseases.