Previously, senolytics, which are therapies aimed at removing senescent cells, targeted the apoptosis (self-destruction) pathway, which is also present in normal cells, leading to low specificity and concerns about numerous side effects. However, research on vaccines targeting GPNMB, an aging antigen specifically expressed on aged vascular endothelial cells, has been progressing.
First, to identify aging antigens specifically expressed on senescent cells, the genetic information of aged human vascular endothelial cells was analyzed. Among them, GPNMB, which was already suggested to be associated with human aging, was found to significantly increase not only in aged human vascular endothelial cells but also in blood vessels of arterial sclerosis model mice, aged mice, and blood vessels of elderly patients with arterial sclerosis.
Next, a genetically modified mouse model was created, allowing the selective removal of GPNMB-positive senescent cells through pharmacological agents. After administering a high-fat diet, an experiment was conducted to selectively remove GPNMB-positive senescent cells using these agents. The experiment showed improvements in glucose metabolism abnormalities associated with obesity and arterial sclerosis.
Therefore, it is believed that a senolytic vaccine targeting GPNMB-positive senescent cells selectively could potentially contribute to the improvement of age-related diseases.
Dr. Munenori Matsuzawa
Aoyama Medical Clinic
References： 1)Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strainsExp Cell Res. 1961; 25: 585-621. 2)Suda M, et alSenolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice.Nature Aging. 2021; 1: 1117-1126