Age-related changes in calcium ion influx and efflux capacity of human dermal fibroblasts

TL;DR

This study shows how aging affects calcium balance in skin cells, which may contribute to cellular aging and increased actin content.

Contribution

The study reveals age-related functional changes in calcium channels and their link to F-actin accumulation in human dermal fibroblasts.

Findings

Older fibroblasts show reduced calcium influx and faster efflux compared to younger cells.

These changes may inhibit gelsolin activity and increase F-actin content in aged cells.

Abstract

Calcium ions (Ca²⁺) are ubiquitous signaling molecules that play important roles as messengers controlling a variety of cellular functions in eukaryotes. Intracellular Ca²⁺ is tightly regulated by a complex interplay between channels, pumps, and exchangers. Aging disrupts Ca²⁺ homeostasis, contributing to age-related diseases, such as neurodegenerative disorders. Previous studies have highlighted the role of Ca²⁺ in regulating actin cytoskeletal proteins in human dermal fibroblasts (HDFs). In this study, we investigated the effect of age on Ca²⁺ influx and efflux in HDFs to test the hypothesis that age-related perturbations in Ca²⁺ homeostasis are correlated with increased F-actin content in aged HDFs. We observed that aging leads to quantitative and functional changes in Ca²⁺ channels, resulting in differences in Ca²⁺ dynamics. Older HDFs showed reduced Ca²⁺ influx and accelerated outflow compared to neonatal and young cells, potentially inhibiting gelsolin activity and increasing F-actin content. Although Ca²⁺ alone cannot fully explain the age-dependent F-actin changes, our findings suggest that it plays an important role in cellular senescence.

The online version contains supplementary material available at 10.1186/s12964-026-02678-6.

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