Potential of Senolytic Vaccines for Age-Related Diseases

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

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松澤 宗範青山メディカルクリニック 院長

近畿大学医学部卒業。慶應義塾大学病院形成外科入局し、佐野厚生総合病院形成外科へ。その後、横浜市立市民病院形成外科として務める。埼玉医科総合医療センター形成外科・美容外科を経て、銀座美容外科クリニック新宿院院長として従事する。その後、青山メディカルクリニック開設し、今に至る。

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