Male rat leukocyte population dynamics predict a window for intervention in aging
Many age-associated changes in the human hematopoietic system have been reproduced in murine models; however, such changes have not been as robustly explored in rats despite the fact these larger rodents are more physiologically similar to humans. We examined peripheral blood of male F344 rats rangi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/76808 |
| _version_ | 1818025809609228288 |
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| author | Hagai Yanai Christopher Dunn Bongsoo Park Christopher Coletta Ross A McDevitt Taylor McNeely Michael Leone Robert P Wersto Kathy A Perdue Isabel Beerman |
| author_facet | Hagai Yanai Christopher Dunn Bongsoo Park Christopher Coletta Ross A McDevitt Taylor McNeely Michael Leone Robert P Wersto Kathy A Perdue Isabel Beerman |
| author_sort | Hagai Yanai |
| collection | DOAJ |
| description | Many age-associated changes in the human hematopoietic system have been reproduced in murine models; however, such changes have not been as robustly explored in rats despite the fact these larger rodents are more physiologically similar to humans. We examined peripheral blood of male F344 rats ranging from 3 to 27 months of age and found significant age-associated changes with distinct leukocyte population shifts. We report CD25+ CD4+ population frequency is a strong predictor of healthy aging, generate a model using blood parameters, and find rats with blood profiles that diverge from chronologic age indicate debility; thus, assessments of blood composition may be useful for non-lethal disease profiling or as a surrogate measure for efficacy of aging interventions. Importantly, blood parameters and DNA methylation alterations, defined distinct juncture points during aging, supporting a non-linear aging process. Our results suggest these inflection points are important considerations for aging interventions. Overall, we present rat blood aging metrics that can serve as a resource to evaluate health and the effects of interventions in a model system physiologically more reflective of humans. |
| first_indexed | 2024-12-10T04:22:01Z |
| format | Article |
| id | doaj.art-59f23ad914a34093b52e8e4b94e793e7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:22:01Z |
| publishDate | 2022-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-59f23ad914a34093b52e8e4b94e793e72022-12-22T02:02:23ZengeLife Sciences Publications LtdeLife2050-084X2022-05-011110.7554/eLife.76808Male rat leukocyte population dynamics predict a window for intervention in agingHagai Yanai0https://orcid.org/0000-0003-1742-5411Christopher Dunn1https://orcid.org/0000-0001-7899-0110Bongsoo Park2Christopher Coletta3Ross A McDevitt4https://orcid.org/0000-0003-3722-9047Taylor McNeely5Michael Leone6Robert P Wersto7Kathy A Perdue8Isabel Beerman9https://orcid.org/0000-0002-7758-8231Epigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, United StatesFlow Cytometry Core, National Institute on Aging, Baltimore, United StatesEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, United StatesComputational Biology and Genomics Core, Laboratory of Genetics & Genomics, National Institute on Aging, Baltimore, United StatesComparative Medicine Section, National Institute on Aging, Baltimore, United StatesEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, United StatesEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, United StatesFlow Cytometry Core, National Institute on Aging, Baltimore, United StatesComparative Medicine Section, National Institute on Aging, Baltimore, United StatesEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, United StatesMany age-associated changes in the human hematopoietic system have been reproduced in murine models; however, such changes have not been as robustly explored in rats despite the fact these larger rodents are more physiologically similar to humans. We examined peripheral blood of male F344 rats ranging from 3 to 27 months of age and found significant age-associated changes with distinct leukocyte population shifts. We report CD25+ CD4+ population frequency is a strong predictor of healthy aging, generate a model using blood parameters, and find rats with blood profiles that diverge from chronologic age indicate debility; thus, assessments of blood composition may be useful for non-lethal disease profiling or as a surrogate measure for efficacy of aging interventions. Importantly, blood parameters and DNA methylation alterations, defined distinct juncture points during aging, supporting a non-linear aging process. Our results suggest these inflection points are important considerations for aging interventions. Overall, we present rat blood aging metrics that can serve as a resource to evaluate health and the effects of interventions in a model system physiologically more reflective of humans.https://elifesciences.org/articles/76808blood compositionagingmethylationhematopoiesisflow cytometryintervention timepoint |
| spellingShingle | Hagai Yanai Christopher Dunn Bongsoo Park Christopher Coletta Ross A McDevitt Taylor McNeely Michael Leone Robert P Wersto Kathy A Perdue Isabel Beerman Male rat leukocyte population dynamics predict a window for intervention in aging eLife blood composition aging methylation hematopoiesis flow cytometry intervention timepoint |
| title | Male rat leukocyte population dynamics predict a window for intervention in aging |
| title_full | Male rat leukocyte population dynamics predict a window for intervention in aging |
| title_fullStr | Male rat leukocyte population dynamics predict a window for intervention in aging |
| title_full_unstemmed | Male rat leukocyte population dynamics predict a window for intervention in aging |
| title_short | Male rat leukocyte population dynamics predict a window for intervention in aging |
| title_sort | male rat leukocyte population dynamics predict a window for intervention in aging |
| topic | blood composition aging methylation hematopoiesis flow cytometry intervention timepoint |
| url | https://elifesciences.org/articles/76808 |
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