Regeneration leads to global tissue rejuvenation in aging sexual planarians
Xiaoting Dai, Xinghua Li, Alexander Tyshkovskiy, Cassandra Zuckerman, Nan Cheng, Peter Bor‐Chian Lin, David Paris, Saad Qureshi, Leonid Kruglyak, Xiaoming Mao, Jayakrishnan Nandakumar, Vadim N. Gladyshev, Scott D. Pletcher, Jacob Sobota, Longhua Guo
Abstract
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.