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Is the anti-aging effect of ACE2 due to its role in the renin-angiotensin system?—Findings from a comparison of the aging phenotypes of ACE2-deficient, Tsukuba hypertensive, and Mas-deficient mice—

Hypertension Research volume 46, pages 1210–1220 (2023)Cite this article

Abstract

Angiotensin converting enzyme 2 (ACE2) functions as an enzyme that produces angiotensin 1-7 (A1-7) from angiotensin II (AII) in the renin-angiotensin system (RAS). We evaluated aging phenotypes, especially skeletal muscle aging, in ACE2 systemically deficient (ACE2 KO) mice and found that ACE2 has an antiaging function. The characteristic aging phenotype observed in ACE2 KO mice was not reproduced in mice deficient in the A1-7 receptor Mas or in Tsukuba hypertensive mice, a model of chronic AII overproduction, suggesting that ACE2 has a RAS-independent antiaging function. In this review, the results we have obtained and related studies on the aging regulatory mechanism mediated by RAS components will be presented and summarized.

We evaluated the aging phenotype of ACE2 systemically deficient (ACE2 KO) mice, particularly skeletal muscle aging, and found that ACE2 has an antiaging function. The characteristic aging phenotype observed in ACE2 KO mice was not reproduced in Mas KO mice, angiotensin 1-7 receptor-deficient mice or in Tsukuba hypertensive mice, a model of chronic angiotensin II overproduction, suggesting that the antiaging functions of ACE2 are independent of the renin-angiotensin system (RAS).

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Acknowledgements

We are most grateful to Hikari Kitamura and Yoshinori Koishi for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Hikari Takeshita, Koichi Yamamoto, Satoko Nozato & Hiromi Rakugi

  2. Department of Medical Science Technology, Faculty of Medical Science Technology, Morinomiya University of Medical Sciences, Osaka, Osaka, Japan

    Hikari Takeshita

  3. Department of Pharmacology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan

    Masaki Mogi

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  1. Hikari Takeshita
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Takeshita, H., Yamamoto, K., Mogi, M. et al. Is the anti-aging effect of ACE2 due to its role in the renin-angiotensin system?—Findings from a comparison of the aging phenotypes of ACE2-deficient, Tsukuba hypertensive, and Mas-deficient mice—. Hypertens Res 46, 1210–1220 (2023). https://doi.org/10.1038/s41440-023-01189-y

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