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Multi-omic rejuvenation and lifespan extension on exposure to youthful circulation
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Abstract
Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs. Old detached mice exhibited improved physiological parameters and lived longer than control isochronic mice. HPB drastically reduced the epigenetic age of blood and liver based on several clock models using two independent platforms. Remarkably, this rejuvenation effect persisted even after 2 months of detachment. Transcriptomic and epigenomic profiles of anastomosed mice showed an intermediate phenotype between old and young, suggesting a global multi-omic rejuvenation effect. In addition, old HPB mice showed gene expression changes opposite to aging but akin to several life span-extending interventions. Altogether, we reveal that long-term HPB results in lasting epigenetic and transcriptome remodeling, culminating in the extension of life span and health span.
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“young blood prolongs the BA of aged recipients via epigenetic remodelling447 and rejuvenates various organs, including the brain.379,448”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [447]
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Metadata
- Authors
- Zhang, B., Lee, D. E., Trapp, A., Tyshkovskiy, A., Lu, A. T., Bareja, A., Kerepesi, C., McKay, L. K., Shindyapina, A. V., Dmitriev, S. E., Baht, G. S., Horvath, S., Gladyshev, V. N., & White, J. P.
- Affiliations
- Brigham and Women's Hospital (US)
- Duke University (US)
- University of California, Los Angeles (US)
- University of North Carolina at Chapel Hill (US)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Gladyshev, Vadim N.
- White, James P.
- ORCID
- Venue
- Nature Aging
- Published
- 2023-07-27
- Volume
- 3
- Issue
- 8
- Pages
- 948-964
- ISSN
- 2662-8465 (ISSN-L)
- PMC
- PMC11095548
- OpenAlex
- W4385302610
- Cited by
- 134
- References
- 81
- Citations by year
- 2026: 31 · 2025: 41 · 2024: 48 · 2023: 13
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Aging (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- SZTAKI Publication Repository (Hungarian Academy of Sciences) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (K01AG056664, R01AG067782, R21AG065943, R01AG065403, P01AG047200)
- National Heart, Lung, and Blood Institute (T32HL007057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- heterochronic parabiosis, rejuvenation, lifespan extension, healthspan, epigenetic aging, transcriptomic remodeling, age-related diseases, multi-omics profiling
- MeSH terms
- Multiomics, Aging, Animals, Longevity, Rejuvenation, Mice
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