Bioelectric characterization of senescing human keratinocytes

Summary: Aging disrupts tissue integrity through the accumulation of senescent cells that impair morphology, signaling, and regeneration. We investigated how bioelectric signaling, specifically resting membrane potential (Vmem), guides the transition to senescence in human keratinocytes. Using volta...

Full description

Saved in:
Bibliographic Details
Main Authors: Hamid Sediqi, Michael Levin
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225015366
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849229274662305792
author Hamid Sediqi
Michael Levin
author_facet Hamid Sediqi
Michael Levin
author_sort Hamid Sediqi
collection DOAJ
description Summary: Aging disrupts tissue integrity through the accumulation of senescent cells that impair morphology, signaling, and regeneration. We investigated how bioelectric signaling, specifically resting membrane potential (Vmem), guides the transition to senescence in human keratinocytes. Using voltage-sensitive dyes, we tracked Vmem alongside senescence markers, chromatin state, and senescence-associated secretory phenotype (SASP) cytokines. Senescence was marked by depolarization, increased inter-culture heterogeneity, reduced intra-culture variability, and loss of spatial Vmem organization. SASP activation was partial: depolarization selectively enhanced interleukin-6 (IL-6) but not IL-1α or IL-8, indicating Vmem shapes the senescent secretome. Senescent cells showed reduced responsiveness to hyperpolarizing drug pinacidil and impaired bioelectric resilience. Hyperpolarization attenuated, and depolarization exacerbated, senescence-associated phenotypes. These findings support the morphostatic information loss theory, which posits that aging results from breakdown of bioelectrically encoded cues that preserve tissue structure. Vmem emerges as a low-dimensional integrator of cell state and spatial order, offering a biophysical target to delay senescence and maintain tissue coordination.
format Article
id doaj-art-f1ec779b53ad4ca8a4e067e626cbdfd0
institution Kabale University
issn 2589-0042
language English
publishDate 2025-09-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-f1ec779b53ad4ca8a4e067e626cbdfd02025-08-22T04:57:08ZengElsevieriScience2589-00422025-09-0128911327510.1016/j.isci.2025.113275Bioelectric characterization of senescing human keratinocytesHamid Sediqi0Michael Levin1Allen Discovery Center at Tufts University, Medford, MA 02155, USAAllen Discovery Center at Tufts University, Medford, MA 02155, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Corresponding authorSummary: Aging disrupts tissue integrity through the accumulation of senescent cells that impair morphology, signaling, and regeneration. We investigated how bioelectric signaling, specifically resting membrane potential (Vmem), guides the transition to senescence in human keratinocytes. Using voltage-sensitive dyes, we tracked Vmem alongside senescence markers, chromatin state, and senescence-associated secretory phenotype (SASP) cytokines. Senescence was marked by depolarization, increased inter-culture heterogeneity, reduced intra-culture variability, and loss of spatial Vmem organization. SASP activation was partial: depolarization selectively enhanced interleukin-6 (IL-6) but not IL-1α or IL-8, indicating Vmem shapes the senescent secretome. Senescent cells showed reduced responsiveness to hyperpolarizing drug pinacidil and impaired bioelectric resilience. Hyperpolarization attenuated, and depolarization exacerbated, senescence-associated phenotypes. These findings support the morphostatic information loss theory, which posits that aging results from breakdown of bioelectrically encoded cues that preserve tissue structure. Vmem emerges as a low-dimensional integrator of cell state and spatial order, offering a biophysical target to delay senescence and maintain tissue coordination.http://www.sciencedirect.com/science/article/pii/S2589004225015366Biological sciencesBiotechnologyBioengineering
spellingShingle Hamid Sediqi
Michael Levin
Bioelectric characterization of senescing human keratinocytes
iScience
Biological sciences
Biotechnology
Bioengineering
title Bioelectric characterization of senescing human keratinocytes
title_full Bioelectric characterization of senescing human keratinocytes
title_fullStr Bioelectric characterization of senescing human keratinocytes
title_full_unstemmed Bioelectric characterization of senescing human keratinocytes
title_short Bioelectric characterization of senescing human keratinocytes
title_sort bioelectric characterization of senescing human keratinocytes
topic Biological sciences
Biotechnology
Bioengineering
url http://www.sciencedirect.com/science/article/pii/S2589004225015366
work_keys_str_mv AT hamidsediqi bioelectriccharacterizationofsenescinghumankeratinocytes
AT michaellevin bioelectriccharacterizationofsenescinghumankeratinocytes