Rejuvenating aged osteoprogenitors for bone repair
Aging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging ne...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/104068 |
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| author | Joshua Reeves Pierre Tournier Pierre Becquart Robert Carton Yin Tang Alessandra Vigilante Dong Fang Shukry J Habib |
| author_facet | Joshua Reeves Pierre Tournier Pierre Becquart Robert Carton Yin Tang Alessandra Vigilante Dong Fang Shukry J Habib |
| author_sort | Joshua Reeves |
| collection | DOAJ |
| description | Aging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging negatively impacts the calvarial bone structure and its osteogenic tissues, diminishing osteoprogenitor number and function and severely impairing bone formation. Notably, increasing osteogenic cell numbers locally fails to rescue repair in aged mice, identifying the presence of intrinsic cellular deficits. Our strategy combines Wnt-mediated osteoprogenitor expansion with intermittent fasting, which leads to a striking restoration of youthful levels of bone healing. We find that intermittent fasting improves osteoprogenitor function, benefits that can be recapitulated by modulating NAD+-dependent pathways or the gut microbiota, underscoring the multifaceted nature of this intervention. Mechanistically, we identify mitochondrial dysfunction as a key component in age-related decline in osteoprogenitor function and show that both cyclical nutrient deprivation and Nicotinamide mononucleotide rejuvenate mitochondrial health, enhancing osteogenesis. These findings offer a promising therapeutic avenue for restoring youthful bone repair in aged individuals, with potential implications for rejuvenating other tissues. |
| format | Article |
| id | doaj-art-9b1b5889dc7b41bbbdc91b0ac36c230d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-9b1b5889dc7b41bbbdc91b0ac36c230d2024-12-18T15:44:00ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.104068Rejuvenating aged osteoprogenitors for bone repairJoshua Reeves0Pierre Tournier1https://orcid.org/0000-0001-7593-6928Pierre Becquart2https://orcid.org/0000-0003-1462-0406Robert Carton3Yin Tang4Alessandra Vigilante5https://orcid.org/0000-0002-8768-8287Dong Fang6Shukry J Habib7https://orcid.org/0000-0003-3132-2216Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland; Centre for Gene Therapy and Regenerative Medicine King’s College London, London, United KingdomDepartment of Biomedical Sciences, University of Lausanne, Lausanne, SwitzerlandDepartment of Biomedical Sciences, University of Lausanne, Lausanne, SwitzerlandCentre for Gene Therapy and Regenerative Medicine King’s College London, London, United KingdomZhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute Zhejiang University, Zhejiang, China; Department of Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, ChinaCentre for Gene Therapy and Regenerative Medicine King’s College London, London, United KingdomZhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute Zhejiang University, Zhejiang, China; Department of Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, ChinaDepartment of Biomedical Sciences, University of Lausanne, Lausanne, SwitzerlandAging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging negatively impacts the calvarial bone structure and its osteogenic tissues, diminishing osteoprogenitor number and function and severely impairing bone formation. Notably, increasing osteogenic cell numbers locally fails to rescue repair in aged mice, identifying the presence of intrinsic cellular deficits. Our strategy combines Wnt-mediated osteoprogenitor expansion with intermittent fasting, which leads to a striking restoration of youthful levels of bone healing. We find that intermittent fasting improves osteoprogenitor function, benefits that can be recapitulated by modulating NAD+-dependent pathways or the gut microbiota, underscoring the multifaceted nature of this intervention. Mechanistically, we identify mitochondrial dysfunction as a key component in age-related decline in osteoprogenitor function and show that both cyclical nutrient deprivation and Nicotinamide mononucleotide rejuvenate mitochondrial health, enhancing osteogenesis. These findings offer a promising therapeutic avenue for restoring youthful bone repair in aged individuals, with potential implications for rejuvenating other tissues.https://elifesciences.org/articles/104068osteoprogenitorsagingrejuvenationintermittent fastingboneWnt |
| spellingShingle | Joshua Reeves Pierre Tournier Pierre Becquart Robert Carton Yin Tang Alessandra Vigilante Dong Fang Shukry J Habib Rejuvenating aged osteoprogenitors for bone repair eLife osteoprogenitors aging rejuvenation intermittent fasting bone Wnt |
| title | Rejuvenating aged osteoprogenitors for bone repair |
| title_full | Rejuvenating aged osteoprogenitors for bone repair |
| title_fullStr | Rejuvenating aged osteoprogenitors for bone repair |
| title_full_unstemmed | Rejuvenating aged osteoprogenitors for bone repair |
| title_short | Rejuvenating aged osteoprogenitors for bone repair |
| title_sort | rejuvenating aged osteoprogenitors for bone repair |
| topic | osteoprogenitors aging rejuvenation intermittent fasting bone Wnt |
| url | https://elifesciences.org/articles/104068 |
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