Regeneration leads to global tissue rejuvenation in aging sexual planarians
The possibility of reversing the adverse impacts of aging could significantly reduce age-related diseases and improve quality of life in older populations. Here we report that the sexual lineage of the planarian Schmidtea mediterranea exhibits physiological decline within 18 months of birth, including altered tissue architecture, impaired fertility and motility, and increased oxidative stress. Single-cell profiling of young and older planarian heads uncovered loss of neurons and muscle, increase of glia, and revealed minimal changes in somatic pluripotent stem cells, along with molecular signatures of aging across tissues. Remarkably, amputation followed by regeneration of lost tissues in older planarians led to reversal of these age-associated changes in tissues both proximal and distal to the injury at physiological, cellular and molecular levels. Our work suggests mechanisms of rejuvenation in both new and old tissues concurring with planarian regeneration, which may provide valuable insights for antiaging interventions.
Authors
- Alexander Tyshkovskiy (ORCID: https://orcid.org/0000-0002-6215-190X)
- Vadim N. Gladyshev (ORCID: https://orcid.org/0000-0002-0372-7016)
- Leonid Kruglyak (ORCID: https://orcid.org/0000-0002-8065-3057)
- Nan Cheng (ORCID: https://orcid.org/0000-0001-5775-7213)
- Peter Bor‐Chian Lin (ORCID: https://orcid.org/0000-0002-8954-9045)
- Jayakrishnan Nandakumar (ORCID: https://orcid.org/0000-0001-9146-2785)
- Cassandra Zuckerman
- Xiaoting Dai (ORCID: https://orcid.org/0000-0002-9033-8691)
- Saqib Qureshi (ORCID: https://orcid.org/0000-0002-0762-6319)
- Scott D. Pletcher (ORCID: https://orcid.org/0000-0002-4812-3785)
- Xinghua Li (ORCID: https://orcid.org/0000-0003-2156-5775)
- Longhua Guo (ORCID: https://orcid.org/0000-0001-9690-9750)
- Xiaoming Mao (ORCID: https://orcid.org/0000-0001-7920-3991)
- David Paris
- Jacob Sobota (ORCID: https://orcid.org/0000-0002-9198-5495)
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- University of Michigan (US)
- Michigan Medicine (US)
Publication Details
- Journal
- Nature Aging
- Published
- 2025-04-03
- DOI
- https://doi.org/10.1038/s43587-025-00847-9
- Citations
- 10
- Primary Topic
- Planarian Biology and Electrostimulation
- Type
- article
- Field-Weighted Citation Impact
- 8.06
Funders
- Howard Hughes Medical Institute
- Pew Charitable Trusts
- American Federation for Aging Research
- Glenn Foundation for Medical Research
- National Institute on Aging
- National Institute of General Medical Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development