202010,Kawamura

研究発表を行った学会；第17回　幹細胞シンポジウム
2019年5月24日〜25日　淡路夢舞台国際会議場（兵庫）
タイトル； Unique response of the longest-lived rodent, naked mole-rats, to cellular senescence induction.
発表者；河村　佳見氏
（熊本大学　大学院生命科学研究部　老化・健康長寿学講座）
要旨；
The Naked mole-rat (NMR) is a eusocial mammalian species living in the Horn of Africa. The NMR exhibits extraordinary longevity with a maximum lifespan exceeding 30 years, although its body mass is similar to that of the mouse. Moreover, this animal shows delayed aging phenotype: the NMR’s mortality rate does not increase until close to its lifespan, and the NMR maintains high fecundity throughout its lifetime, and also possesses unusual cancer-resistance.
To study the mechanisms of delayed aging phenotype in NMRs, we focused on cellular senescence. Cellular senescence prevents tumorigenesis by permanently arresting the cell cycle of damaged cells. However, the accumulation of senescent cells promotes age-related physiological deterioration and disorders, including cancer. Recently, a paper showed that cellular senescence occurs in vivo developmental process of NMRs and in vitro fibroblasts that received stresses such as DNA damage or oncogene activation (Zhao et al., 2018). However, it is still unclear whether NMR cells go through the same process of senescent cell accumulation as in the case of other mammals. To examine the dynamics of NMR cells after cellular senescence, we induced cellular senescence by several methods such as DNA damage regent treatment, or oncogene overespression activation, and compared their phenotypes with those of mice. Cellular senescence induction increased the percentage of the SA-b-gal-positive cells and the expression level of some senescence marker genes in mice. In contrast, in NMRs, SA-b-gal-positive cells were found only sporadically, and instead, a marked increase of cell death was observed. NMR-specific mechanism inducing cell death in senescent cells would contribute to reduce the accumulation of senescent cells in their bodies during aging. Our findings provide new insights into the mechanisms underlying the delayed aging phenotype of the longest-lived rodent.