Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish
Aging individuals exhibit a pervasive decline in adaptive immune function, with important implications for health and lifespan. Previous studies have found a pervasive loss of immune-repertoire diversity in human peripheral blood during aging; however, little is known about repertoire aging in other...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-02-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/65117 |
| _version_ | 1818018265058770944 |
|---|---|
| author | William John Bradshaw Michael Poeschla Aleksandra Placzek Samuel Kean Dario Riccardo Valenzano |
| author_facet | William John Bradshaw Michael Poeschla Aleksandra Placzek Samuel Kean Dario Riccardo Valenzano |
| author_sort | William John Bradshaw |
| collection | DOAJ |
| description | Aging individuals exhibit a pervasive decline in adaptive immune function, with important implications for health and lifespan. Previous studies have found a pervasive loss of immune-repertoire diversity in human peripheral blood during aging; however, little is known about repertoire aging in other immune compartments, or in species other than humans. Here, we perform the first study of immune-repertoire aging in an emerging model of vertebrate aging, the African turquoise killifish (Nothobranchius furzeri). Despite their extremely short lifespans, these killifish exhibit complex and individualized heavy-chain repertoires, with a generative process capable of producing millions of distinct productive sequences. Whole-body killifish repertoires decline rapidly in within-individual diversity with age, while between-individual variability increases. Large, expanded B-cell clones exhibit far greater diversity loss with age than small clones, suggesting important differences in how age affects different B-cell populations. The immune repertoires of isolated intestinal samples exhibit especially dramatic age-related diversity loss, related to an elevated prevalence of expanded clones. Lower intestinal repertoire diversity was also associated with transcriptomic signatures of reduced B-cell activity, supporting a functional role for diversity changes in killifish immunosenescence. Our results highlight important differences in systemic vs. organ-specific aging dynamics in the adaptive immune system. |
| first_indexed | 2024-04-14T07:36:44Z |
| format | Article |
| id | doaj.art-69e8c6c5d1a04ac594ec678d136d1c60 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:36:44Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-69e8c6c5d1a04ac594ec678d136d1c602022-12-22T02:05:39ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.65117Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifishWilliam John Bradshaw0Michael Poeschla1Aleksandra Placzek2Samuel Kean3Dario Riccardo Valenzano4https://orcid.org/0000-0002-8761-8289Max Planck Institute for Biology of Ageing, Cologne, Germany; University of Cologne, Cologne, GermanyMax Planck Institute for Biology of Ageing, Cologne, GermanyMax Planck Institute for Biology of Ageing, Cologne, GermanyMax Planck Institute for Biology of Ageing, Cologne, GermanyMax Planck Institute for Biology of Ageing, Cologne, Germany; University of Cologne, Cologne, GermanyAging individuals exhibit a pervasive decline in adaptive immune function, with important implications for health and lifespan. Previous studies have found a pervasive loss of immune-repertoire diversity in human peripheral blood during aging; however, little is known about repertoire aging in other immune compartments, or in species other than humans. Here, we perform the first study of immune-repertoire aging in an emerging model of vertebrate aging, the African turquoise killifish (Nothobranchius furzeri). Despite their extremely short lifespans, these killifish exhibit complex and individualized heavy-chain repertoires, with a generative process capable of producing millions of distinct productive sequences. Whole-body killifish repertoires decline rapidly in within-individual diversity with age, while between-individual variability increases. Large, expanded B-cell clones exhibit far greater diversity loss with age than small clones, suggesting important differences in how age affects different B-cell populations. The immune repertoires of isolated intestinal samples exhibit especially dramatic age-related diversity loss, related to an elevated prevalence of expanded clones. Lower intestinal repertoire diversity was also associated with transcriptomic signatures of reduced B-cell activity, supporting a functional role for diversity changes in killifish immunosenescence. Our results highlight important differences in systemic vs. organ-specific aging dynamics in the adaptive immune system.https://elifesciences.org/articles/65117agingantibody diversitykillifishturquoise killifishimmunosenescenceimmunoglobulin |
| spellingShingle | William John Bradshaw Michael Poeschla Aleksandra Placzek Samuel Kean Dario Riccardo Valenzano Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish eLife aging antibody diversity killifish turquoise killifish immunosenescence immunoglobulin |
| title | Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish |
| title_full | Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish |
| title_fullStr | Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish |
| title_full_unstemmed | Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish |
| title_short | Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish |
| title_sort | extensive age dependent loss of antibody diversity in naturally short lived turquoise killifish |
| topic | aging antibody diversity killifish turquoise killifish immunosenescence immunoglobulin |
| url | https://elifesciences.org/articles/65117 |
| work_keys_str_mv | AT williamjohnbradshaw extensiveagedependentlossofantibodydiversityinnaturallyshortlivedturquoisekillifish AT michaelpoeschla extensiveagedependentlossofantibodydiversityinnaturallyshortlivedturquoisekillifish AT aleksandraplaczek extensiveagedependentlossofantibodydiversityinnaturallyshortlivedturquoisekillifish AT samuelkean extensiveagedependentlossofantibodydiversityinnaturallyshortlivedturquoisekillifish AT darioriccardovalenzano extensiveagedependentlossofantibodydiversityinnaturallyshortlivedturquoisekillifish |