Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model

Akitoshi Mitani; Hiroshi Iwai; Muneo Inaba; Dan Van Bui; Toru Miwa; Linh Manh Nguyen; Chu Hong Hanh; Tomofumi Sakagami; Kensuke Suzuki; Yoshiki Kobayashi; Yasutaka Yun; Yuuki Sugita; Akira Kanda

doi:10.1016/j.exger.2023.112184

Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model

Exp Gerontol. 2023 Jun 15:177:112184. doi: 10.1016/j.exger.2023.112184. Epub 2023 May 4.

Authors

Akitoshi Mitani¹, Hiroshi Iwai², Muneo Inaba³, Dan Van Bui⁴, Toru Miwa⁵, Linh Manh Nguyen⁶, Chu Hong Hanh⁷, Tomofumi Sakagami⁸, Kensuke Suzuki⁹, Yoshiki Kobayashi¹⁰, Yasutaka Yun¹¹, Yuuki Sugita¹², Akira Kanda¹³

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: mitaniak@hirakata.kmu.ac.jp.
² Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: iwai@hirakata.kmu.ac.jp.
³ First Department of Medicine, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: inabam@hirakata.kmu.ac.jp.
⁴ Department of Allergy & Clinical Immunology, Hanoi Medical University, 1 Ton That Tung, Kim Lien, Dong Da, Hanoi, Viet Nam; Department of Allergy, Immunology and Dermatology, E Hospital, 89 Tran Cung Street, Nghia Tan, Cau Giay, Hanoi, Viet Nam. Electronic address: buivandan@hmu.edu.vn.
⁵ Department of Otolaryngology, Head and Neck Surgery, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. Electronic address: t-miwa@omu.ac.jp.
⁶ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: nguyenli@hirakata.kmu.ac.jp.
⁷ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: chuh@hirakata.kmu.ac.jp.
⁸ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: sakagato@hirakata.kmu.ac.jp.
⁹ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: suzukken@hirakata.kmu.ac.jp.
¹⁰ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan; Allergy Center, Kansai Medical University Hospital, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: kobayosh@hirakata.kmu.ac.jp.
¹¹ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan; Allergy Center, Kansai Medical University Hospital, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: yunys@hirakata.kmu.ac.jp.
¹² Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: sugitayk@hirakata.kmu.ac.jp.
¹³ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan; Laboratory Medicine Center, Kansai Medical University Hospital, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan; Allergy Center, Kansai Medical University Hospital, 2-5-1 Shimmachi, Hitrakata, Osaka 573-1010, Japan. Electronic address: akanda@hirakata.kmu.ac.jp.

PMID: 37105504
DOI: 10.1016/j.exger.2023.112184

Abstract

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.

Keywords: Hearing loss; Nitric oxide; Rejuvenation; Senescence; Spiral ganglion; T lymphocytes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology
Animals
Cochlea
Disease Models, Animal
Lymphocytes
Mice
Presbycusis* / prevention & control

Abstract

Publication types

MeSH terms

Grants and funding