Arginase-ii deficiency extends lifespan in mice

Xiong, Yuyan; Yepuri, Gautham; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

doi:10.3389/fphys.2017.00682

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Arginase-ii deficiency extends lifespan in mice

Xiong, Yuyan Division of Physiology, Cardiovascular and Aging Research, Department of Medicine, University of Fribourg, Switzerland
Yepuri, Gautham Division of Physiology, Cardiovascular and Aging Research, Department of Medicine, University of Fribourg, Switzerland
Montani, Jean-Pierre Division of Physiology, Cardiovascular and Aging Research, Department of Medicine, University of Fribourg, Switzerland - National Center of Competence in Research “Kidney.CH”, Fribourg, Switzerland
Ming, Xiu-Fen Division of Physiology, Cardiovascular and Aging Research, Department of Medicine, University of Fribourg, Switzerland - National Center of Competence in Research “Kidney.CH”, Fribourg, Switzerland
Yang, Zhihong Division of Physiology, Cardiovascular and Aging Research, Department of Medicine, University of Fribourg, Switzerland - National Center of Competence in Research “Kidney.CH”, Fribourg, Switzerland

2017

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Frontiers in Physiology. - 2017, vol. 8, p. 682

English The mitochondrial arginase type II (Arg-II) has been shown to interact with ribosomal protein S6 kinase 1 (S6K1) and mitochondrial p66Shc and to promote cell senescence, apoptosis and inflammation under pathological conditions. However, the impact of Arg-II on organismal lifespan is not known. In this study, we demonstrate a significant lifespan extension in mice with Arg-II gene deficiency (Arg-II-/-) as compared to wild type (WT) control animals. This effect is more pronounced in the females than in the males. The gender difference is associated with higher Arg-II expression levels in the females than in the males in skin and heart at both young and old age. Ablation of Arg-II gene significantly reduces the aging marker p16INK4a levels in these tissues of old female mice, whereas in the male mice this effect of Arg- II deficiency is weaker. In line with this observation, age-associated increases in S6K1 signaling and p66Shc levels in heart are significantly attenuated in the female Arg-II-/- mice. In the male mice, only p66Shc but not S6K1 signaling is reduced. In summary, our study demonstrates that Arg-II may play an important role in the acceleration of aging in mice. Genetic disruption of Arg-II in mouse extends lifespan predominantly in females, which relates to inhibition of S6K1, p66Shc, and p16INK4a. Thus, Arg-II may represent a promising target to decelerate aging process and extend lifespan as well as to treat age-related diseases.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

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