Electrical stimulation promotes longevity and regeneration in a colonial chordate
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Jos Domen
Biology Department, Stanford University, Hopkins Marine Station
Yotam Voskoboynik
Department of Bioinformatics and System Biology, Jacobs School of Engineering, University of California
Tom Levy
Biology Department, Stanford University, Hopkins Marine Station
Erica M. Domen
Department of Integrative Biology, University of California
Katherine J. Ishizuka
Biology Department, Stanford University, Hopkins Marine Station
Karla J. Palmeri
Biology Department, Stanford University, Hopkins Marine Station
Chiara Anselmi
Biology Department, Stanford University, Hopkins Marine Station
Thomas Rolander
Biology Department, Stanford University, Hopkins Marine Station
Norma F. Neff
Chan Zuckerberg Biohub SF
Angela M. Detweiler
Chan Zuckerberg Biohub SF
Irving L. Weissman
Kimberly L. Gandy
Biology Department, Stanford University, Hopkins Marine Station
Debashis Sahoo
Department of Pediatrics, University of California
Ayelet Voskoboynik
Biology Department, Stanford University, Hopkins Marine Station