Electrical stimulation promotes longevity and regeneration in a colonial chordate

• 成果类型: Article
• 署名作者: Domen, Jos; Voskoboynik, Yotam; Levy, Tom; Domen, Erica M.; Ishizuka, Katherine J.; Palmeri, Karla J.; Anselmi, Chiara; Rolander, Thomas; Neff, Norma F.; Detweiler, Angela M.; Weissman, Irving L.; Gandy, Kimberly L.; Sahoo, Debashis; Voskoboynik, Ayelet
• 署名单位: Stanford University; Stanford Medicine; Stanford University; Stanford University; University of California System; University of California San Diego; University of California System; University of California Berkeley; Chan Zuckerberg Initiative (CZI); University of California System; University of California San Diego; University of California System; University of California San Diego
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2610968123
• 发表日期: 2026-06-02
• 页码: e2610968123
• 关键词: pulsatile electrical current; rejuvenation; stem cell aging; longevity; tunicate; HEMATOPOIETIC STEM-CELLS; ASCIDIAN BOTRYLLUS-SCHLOSSERI; BLASTOGENETIC CYCLE; natural-selection; life-span; units; germ; ALLORECOGNITION; identification; mechanisms

摘要

Endogenous bioelectric currents regulate development and regeneration, but their influence on organismal longevity and stem cell-mediated repair is not well understood. We demonstrate that a brief, clinically safe pulse of electrical current (PEC) produces lasting rejuvenation in the colonial chordate Botryllus schlosseri. In this species where all differentiated tissues are replaced weekly and progenitor populations mediate the weekly de novo generation of new organs, organismal aging is directly driven by alterations of the precursor pool. Electrically stimulated colonies exhibited increased growth, enhanced reproductive activity, and significantly improved survival, along with improved stem cell associated function. Whole-transcriptome analysis revealed a biphasic reboot and rebound program across all functional paths. An acute 2-h reboot was defined by the synchronized downregulation of the genomic engine, mitochondrial respiratory chain, contractile apparatus, and extracellular matrix (ECM) integrity. This systemic pause transitioned into a massive 24-h rebound, characterized by the global reactivation of these paths, including a metabolic surge, cytoskeletal rebuilding, and ECM scaffold synthesis. Notably, PEC induced a conserved immunometabolic shift from a proinflammatory to a reparative signature, mimicking exercise-induced shifts observed in mammals. Our findings identify that PEC acts directly on progenitor-cell-driven pathways to restore homeostatic vitality, offering insights into the reversal of age-related decline.