ダマラランドデバネズミの強い発がん耐性を世界で初めて実証 ー近縁のハダカデバネズミと共通する「がんになりにくさ」、異なる防御戦略ー

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2026-10-26 九州大学

九州大学、熊本大学などの研究グループは、長寿動物ダマラランドデバネズミが、近縁種のハダカデバネズミと同様に、化学発がん物質に対して強い発がん耐性を持つことを世界で初めて実証した。2種類の化学発がん誘導実験を実施し、最長3年を超えて観察した結果、ダマラランドデバネズミでは腫瘍の発生が一例も確認されなかった。一方、発がん刺激に対する組織の免疫応答は両種で異なっていた。ハダカデバネズミでは免疫細胞の集積が起こりにくいのに対し、ダマラランドデバネズミでは組織中の免疫細胞が顕著に増加し、免疫の活性化と抑制に関わる遺伝子の発現も増加した。両種は共通して高い発がん耐性を持ちながら、異なる防御戦略を用いる可能性が示された。本成果は、動物種間の比較を通じて発がんを防ぐ生体機構の理解を深め、将来のがん予防・治療法や老化研究に新たな手がかりをもたらすことが期待される。

ダマラランドデバネズミの強い発がん耐性を世界で初めて実証 ー近縁のハダカデバネズミと共通する「がんになりにくさ」、異なる防御戦略ー
研究室で飼育されているダマラランドデバネズミ

<関連情報>

アフリカに生息する長寿の2種のハダカデバネズミ(ハダカデバネズミとダマラランドデバネズミ)は、がんに対する抵抗性は共通しているものの、免疫応答は異なっている Shared cancer resistance but divergent immune responses in two long-lived African mole-rat species: the naked mole-rat and the Damaraland mole-rat

Koki Sekiguchi, Kaori Oka, Mari Nagase, Yui Sano, Maki Nakamoto, Kurumi Ota, Kazuki Nakamura, Mika Kobe, Naho Onoue, Nanami Inoue, Tsubasa Mikawa, Yusuke Sakai, Satoko Sakurai, Yukio Fujiwara, Yoshimi Kawamura, Takuya Yamamoto, Rochelle Buffenstein, Yoshihiro Komohara & Kyoko Miura
GeoScience  Published:26 October 2026
DOI:https://doi.org/10.1007/s11357-026-02576-2

Abstract

Several exceptionally long-lived mammals show natural resistance to cancer. The longest-lived rodent, the naked mole-rat (NMR; Heterocephalus glaber) is renowned for its remarkable resistance to carcinogenesis; however, it is unclear whether other long-lived African mole-rat species are also cancer-resistant, and whether they exhibit similar responses to chemical carcinogens. Here, we demonstrate that a long-lived, close relative of the NMR, the Damaraland mole-rat (DMR; Fukomys damarensis), is also highly resistant to skin carcinogenesis induced by two different chemical carcinogens. Strikingly, DMRs developed no tumors over a period of more than 3 years. Despite sharing a cancer-resistant phenotype, the two species exhibit markedly different immune responses. After exposure to carcinogens, DMRs show robust immune cell infiltration, whereas NMRs exhibit only minimal immune cell infiltration. At the transcriptomic level, these differences were even more pronounced. DMRs upregulated genes associated with both T cell-mediated and innate immune responses, reflecting broad immune activation, while simultaneously upregulating immunosuppressive molecules that may restrain excessive inflammatory responses. By contrast, NMRs showed limited transcriptional changes, instead engaging the keratinization and p53-related stress pathways, consistent with attenuated inflammation and potentially reflecting a distinct tissue-protective strategy. Both species, however, showed low expression of Toll-like receptor genes and loss of necroptosis induction, which may mitigate cancer-promoting tissue inflammation. Together, these findings indicate that closely related cancer-resistant African mole-rat species can exhibit divergent immune responses despite similar life-history traits and shared evolutionary history, highlighting the diversity of biological pathways associated with cancer resistance in long-lived mammals.

医療・健康
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