Electrical stimulation promotes longevity and regeneration in a colonial chordate

J Jos Domen (Biology Department, Stanford University, Hopkins Marine Station) Y Yotam Voskoboynik (Department of Bioinformatics and System Biology, Jacobs School of Engineering, University of California) T Tom Levy (Biology Department, Stanford University, Hopkins Marine Station) E Erica M. Domen (Department of Integrative Biology, University of California) K Katherine J. Ishizuka (Biology Department, Stanford University, Hopkins Marine Station) K Karla J. Palmeri (Biology Department, Stanford University, Hopkins Marine Station) C Chiara Anselmi (Biology Department, Stanford University, Hopkins Marine Station) T Thomas Rolander (Biology Department, Stanford University, Hopkins Marine Station) N Norma F. Neff (Chan Zuckerberg Biohub SF) A Angela M. Detweiler (Chan Zuckerberg Biohub SF) I Irving L. Weissman K Kimberly L. Gandy (Biology Department, Stanford University, Hopkins Marine Station) D Debashis Sahoo (Department of Pediatrics, University of California) A Ayelet Voskoboynik (Biology Department, Stanford University, Hopkins Marine Station)

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

Volume / Issue Vol. 123, Issue 22
Published June 02, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (14)

J

Jos Domen

Biology Department, Stanford University, Hopkins Marine Station

Y

Yotam Voskoboynik

Department of Bioinformatics and System Biology, Jacobs School of Engineering, University of California

T

Tom Levy

Biology Department, Stanford University, Hopkins Marine Station

E

Erica M. Domen

Department of Integrative Biology, University of California

K

Katherine J. Ishizuka

Biology Department, Stanford University, Hopkins Marine Station

K

Karla J. Palmeri

Biology Department, Stanford University, Hopkins Marine Station

C

Chiara Anselmi

Biology Department, Stanford University, Hopkins Marine Station

T

Thomas Rolander

Biology Department, Stanford University, Hopkins Marine Station

N

Norma F. Neff

Chan Zuckerberg Biohub SF

A

Angela M. Detweiler

Chan Zuckerberg Biohub SF

I

Irving L. Weissman

K

Kimberly L. Gandy

Biology Department, Stanford University, Hopkins Marine Station

D

Debashis Sahoo

Department of Pediatrics, University of California

A

Ayelet Voskoboynik

Biology Department, Stanford University, Hopkins Marine Station