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Promises of reprogramming-induced rejuvenation
Abstract
Reprogramming-induced rejuvenation (RIR) reverses cellular aging by transiently engaging early reprogramming states without full dedifferentiation. This review examines current developments in the molecular mechanisms, technological advances, and tissue-specific applications of RIR. Recent mechanistic insights highlight persisting questions in timing, heterogeneity, and pathways engaged in the epigenetic response. New technological advances have expanded RIR modalities beyond traditional Yamanaka factors to include mRNA-based delivery, CRISPRa, and chemical cocktails, while high-throughput screening platforms are systematically identifying novel rejuvenation factors with improved safety profiles. Recent tissue-specific applications demonstrate functional restoration across brain, liver, intestine, cardiovascular, and epithelial systems through reversal of cellular senescence, reduction of DNA damage and epigenetic age, and enhanced regenerative capacity. However, clinical translation faces challenges including narrow therapeutic windows, incomplete mechanistic understanding, and limited biomarker standardization. We discuss how single-cell technologies, computational prediction tools, and systematic in vivo testing may advance RIR toward geroscience therapies for age-related diseases.
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Picó, S., Vílchez-Acosta, A., de Sousa, J. A., Maza, M. D. C. L., Parras, A., Desdín-Micó, G., Mrabti, C., Maroun, C. Y., Branchina, C., von Meyenn, F., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.08.584074 · Cited by 1
SENOMORPHIC EFFECT OF GENETIC AND CHEMICAL PARTIAL REPROGRAMMING
Nunez-Quintela, V., Chantrel, J., Prados, M. A., Pedrosa, P., Lorandi, I., Rodriguez, L. L., Chen, C., Paredes, R., Failde-Fiestras, A., Gonzalez-Perez, D., et al. (2026) · doi:10.64898/2026.01.13.699211
Flagged first, then by citations
Research works printed but not linked: 1
- Seninge L, Kummerlowe CS, Reynolds DL, Bernstein N, Kimmel JC: In silico design of epigenetic reprogramming payloads. ICML 2025 Workshop GenBio; 2025. 〈https://openreview.net/forum?id=kPQ6NKVAiT〉.
Cited by
Sorted by citations
Editorial overview: At the edge of plasticity: Decoding cell fate in regeneration and repair
Li, D., & Lee, J.-H. (2026) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2026.102531
Who Gets to Outlive the Present? Rejuvenation and Demographic AuthorityPreprint
Milevski, V. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.7481603
Metadata
- Authors
- Simpson, D. J., Arif, N., Suwanlikit, Y., Kirschner, K., & Chandra, T.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Simpson, Daniel J.
- Kirschner, Kristina
- Chandra, Tamir
- Venue
- Current Opinion in Genetics & Development
- Publisher
- Elsevier BV
- Published
- 2026-08
- Volume
- 99
- Pages
- 102484
- ISSN
- 0959-437X (ISSN-L)
- OpenAlex
- W7161734680
- Cited by
- 2
- References
- 80
- Citations by year
- 2026: 2
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Current Opinion in Genetics & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Robert and Arlene Kogod Center on Aging
- Mayo Clinic
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular aging, Yamanaka factors, CRISPR activation, epigenetic age, DNA damage, tissue regeneration, age-related diseases, geroscience, single-cell technologies, biomarkers
- MeSH terms
- Animals, Humans, Rejuvenation, Cellular Senescence, Epigenesis, Genetic, Cellular Reprogramming
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