Maintenance of systemic immune functions prevents accelerated presbycusis.
There is no effective therapy for progressive hearing loss such as presbycusis, the causes of which remain poorly understood because of the difficulty of separating genetic and environmental contributions. In the present study, we show that the age-related dysfunctions of the systemic immune system in an animal model of accelerated presbycusis (SAMP1, senescence-accelerated mouse P1) can be corrected by allogeneic bone marrow transplantation (BMT). We also demonstrate that this presbycusis can be prevented; BMT protects the recipients from age-related hearing impairment and the degeneration of spiral ganglion cells (SGCs) as well as the dysfunctions of T lymphocytes, which have a close relation to immune senescence. No donor cells are infiltrated to the spiral ganglia, confirming that this experimental system using BMT is connected to the systemic immune system and does not contribute to transdifferentiation or fusion by donor hematopoietic stem cells (HSCs), or to the direct maintenance of ganglion cells by locally infiltrated donor immunocompetent cells. Therefore, another procedure which attempts to prevent the age-related dysfunctions of the recipient immune system is the inoculation of syngeneic splenocytes from young donors. These mice show no development of hearing loss, compared with the recipient mice with inoculation of saline or splenocytes from old donors. Our studies on the relationship between age-related systemic immune dysfunctions and neurodegeneration mechanisms open up new avenues of treatment for presbycusis, for which there is no effective therapy.
Iwai
Hiroshi
H
Department of Otolaryngology, Kansai Medical University, Moriguchi City, Osaka, Japan. iwai@takii.kmu.ac.jp
Baba
Susumu
S
Omae
Mariko
M
Lee
Shinryu
S
Yamashita
Toshio
T
Ikehara
Susumu
S
D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D011304:Presbycusis / Q000276:immunology* / Q000517:prevention & control*; D011601:Psychophysics; D011828:Radiation Chimera; D013136:Spiral Ganglion / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects
D008934:Mitogens; C485184:enhanced green fluorescent protein; D003208:Concanavalin A; D049452:Green Fluorescent Proteins