Multi-organ frailty is enhanced by periodontitis-induced inflammaging

Abstract Background The incidence of periodontitis is high in older individuals. However, its impact on multi-organ frailty remains unclear. We developed mouse models with varying severity and duration of periodontitis to examine its effects. Methods We generated mouse models with mild and severe pe...

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Main Authors: Yoshitaka Kase, Satoru Morikawa, Yuji Okano, Tatsuya Hosoi, Takazumi Yasui, Yoko Taki-Miyashita, Mitsutaka Yakabe, Maraku Goto, Kazuyuki Ishihara, Sumito Ogawa, Taneaki Nakagawa, Hideyuki Okano
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Inflammation and Regeneration
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Online Access:https://doi.org/10.1186/s41232-025-00366-5
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author Yoshitaka Kase
Satoru Morikawa
Yuji Okano
Tatsuya Hosoi
Takazumi Yasui
Yoko Taki-Miyashita
Mitsutaka Yakabe
Maraku Goto
Kazuyuki Ishihara
Sumito Ogawa
Taneaki Nakagawa
Hideyuki Okano
author_facet Yoshitaka Kase
Satoru Morikawa
Yuji Okano
Tatsuya Hosoi
Takazumi Yasui
Yoko Taki-Miyashita
Mitsutaka Yakabe
Maraku Goto
Kazuyuki Ishihara
Sumito Ogawa
Taneaki Nakagawa
Hideyuki Okano
author_sort Yoshitaka Kase
collection DOAJ
description Abstract Background The incidence of periodontitis is high in older individuals. However, its impact on multi-organ frailty remains unclear. We developed mouse models with varying severity and duration of periodontitis to examine its effects. Methods We generated mouse models with mild and severe periodontitis, categorizing the disease duration into 3-month and 5-month periods for analysis. The organs assessed for frailty included the gastrocnemius muscle, soleus muscle, brain, and femur. Results Our study found that periodontitis induced systemic inflammation resembling inflammaging and other symptoms characteristic of age-induced frailty. Notably, muscle impairment developed specifically in slow-twitch muscles, and the femur emerged as the most vulnerable bone, exhibiting reduced bone mineral density even with mild and short-duration periodontitis. This condition resulted in the co-occurrence of bone fragility and slow-twitch muscle dysfunction. Cognitive function assessment revealed increased activated microglia and decreased adult neurogenesis in the hippocampus, impairing spatial learning. Thus, periodontitis induced both physical and cognitive frailties. Therapeutic intervention for the periodontitis, which halted the exacerbation of bone resorption markers, did not restore femur bone mineral density. Conclusion This study underscores the role of periodontitis in inducing multifaceted organ frailty with vulnerability, varying by organ, and the necessity of early intervention, particularly regarding bone density loss.
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series Inflammation and Regeneration
spelling doaj-art-178f53449013430dac5d5038594141b42025-02-09T12:24:54ZengBMCInflammation and Regeneration1880-81902025-02-0145111910.1186/s41232-025-00366-5Multi-organ frailty is enhanced by periodontitis-induced inflammagingYoshitaka Kase0Satoru Morikawa1Yuji Okano2Tatsuya Hosoi3Takazumi Yasui4Yoko Taki-Miyashita5Mitsutaka Yakabe6Maraku Goto7Kazuyuki Ishihara8Sumito Ogawa9Taneaki Nakagawa10Hideyuki Okano11Regenerative Medicine Research Center, Keio UniversityDepartment of Dentistry and Oral Surgery, Keio University School of MedicineDivision of CNS Regeneration and Drug Discovery, International Center for Brain Science (ICBS), Fujita Health UniversityDepartment of Geriatric Medicine, Graduate School of Medicine, The University of TokyoDepartment of Dentistry and Oral Surgery, Keio University School of MedicineDepartment of Dentistry and Oral Surgery, Keio University School of MedicineDepartment of Geriatric Medicine, Graduate School of Medicine, The University of TokyoDivision of CNS Regeneration and Drug Discovery, International Center for Brain Science (ICBS), Fujita Health UniversityDepartment of Microbiology, Tokyo Dental CollegeDepartment of Geriatric Medicine, Graduate School of Medicine, The University of TokyoDepartment of Dentistry and Oral Surgery, Keio University School of MedicineRegenerative Medicine Research Center, Keio UniversityAbstract Background The incidence of periodontitis is high in older individuals. However, its impact on multi-organ frailty remains unclear. We developed mouse models with varying severity and duration of periodontitis to examine its effects. Methods We generated mouse models with mild and severe periodontitis, categorizing the disease duration into 3-month and 5-month periods for analysis. The organs assessed for frailty included the gastrocnemius muscle, soleus muscle, brain, and femur. Results Our study found that periodontitis induced systemic inflammation resembling inflammaging and other symptoms characteristic of age-induced frailty. Notably, muscle impairment developed specifically in slow-twitch muscles, and the femur emerged as the most vulnerable bone, exhibiting reduced bone mineral density even with mild and short-duration periodontitis. This condition resulted in the co-occurrence of bone fragility and slow-twitch muscle dysfunction. Cognitive function assessment revealed increased activated microglia and decreased adult neurogenesis in the hippocampus, impairing spatial learning. Thus, periodontitis induced both physical and cognitive frailties. Therapeutic intervention for the periodontitis, which halted the exacerbation of bone resorption markers, did not restore femur bone mineral density. Conclusion This study underscores the role of periodontitis in inducing multifaceted organ frailty with vulnerability, varying by organ, and the necessity of early intervention, particularly regarding bone density loss.https://doi.org/10.1186/s41232-025-00366-5InflammagingPeriodontitisFrailtyOsteopeniaCognitive declineCognitive frailty
spellingShingle Yoshitaka Kase
Satoru Morikawa
Yuji Okano
Tatsuya Hosoi
Takazumi Yasui
Yoko Taki-Miyashita
Mitsutaka Yakabe
Maraku Goto
Kazuyuki Ishihara
Sumito Ogawa
Taneaki Nakagawa
Hideyuki Okano
Multi-organ frailty is enhanced by periodontitis-induced inflammaging
Inflammation and Regeneration
Inflammaging
Periodontitis
Frailty
Osteopenia
Cognitive decline
Cognitive frailty
title Multi-organ frailty is enhanced by periodontitis-induced inflammaging
title_full Multi-organ frailty is enhanced by periodontitis-induced inflammaging
title_fullStr Multi-organ frailty is enhanced by periodontitis-induced inflammaging
title_full_unstemmed Multi-organ frailty is enhanced by periodontitis-induced inflammaging
title_short Multi-organ frailty is enhanced by periodontitis-induced inflammaging
title_sort multi organ frailty is enhanced by periodontitis induced inflammaging
topic Inflammaging
Periodontitis
Frailty
Osteopenia
Cognitive decline
Cognitive frailty
url https://doi.org/10.1186/s41232-025-00366-5
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