Submandibular gland-specific inflammaging-induced hyposalivation in the male senescence-accelerated mouse prone -1 line (SAM-P1)

  • Yuta Miyagi
  • Yusuke KondoEmail author
  • Yuichiro Kusuda
  • Yusuke Hori
  • Seiya Yamazaki
  • Takashi Munemasa
  • Taro Mukaibo
  • Chihiro Masaki
  • Ryuji Hosokawa
Research Article


Aging has pronounced effects on mammalian tissues and cells, but the impacts of aging on salivary gland function are relatively unknown. This study aims to evaluate the effects of aging on submandibular gland (SMG) and parotid gland (PG) functions in the male senescence-accelerated mouse. In vivo analysis at the systemic level revealed that salivary secretion induced by pilocarpine, a muscarinic agonist, from the SMG was significantly decreased in aged mice, whereas salivary secretion from the PG was not affected. To evaluate organ-level function, the SMG was perfused with the muscarinic agonists carbachol and calcium ionophore A23187 ex vivo to induce salivary secretion, and decreased saliva production was also observed in the aged SMG. Histological analysis revealed the presence of CD4-positive lymphocytes infiltrating the aged SMG. Furthermore, real-time PCR revealed that the aged SMG exhibited accelerated cell aging, increased levels of the inflammatory cytokine interleukin-6, and decreased mRNA levels of the water channel protein aquaporin-5 (AQP5). In summary, these results demonstrate that SMG function in aged mice was diminished, and that cell senescence, chronic inflammation, and the decreased gene expression of AQP5 are the likely causes of hyposalivation in the SMG of aged mice.


Submandibular gland Parotid gland Aging Inflammation Aquaporin 5 Inflammaging 



This work was supported by a Grant from the Japan Society for the Promotion of Science KAKENHI (No. 17K17184).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest associated with this manuscript.

Ethical approval

All experiments were approved by the Animal Committee of Kyushu Dental University.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Division of Oral Reconstruction and RehabilitationKyushu Dental UniversityKitakyushuJapan

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