Vimentin Plays a Crucial Role in Fibroblast Ageing by Regulating Biophysical Properties and Cell Migration.

Sliogeryte Sliogeryte,Gavara Gavara

doi:10.3390/cells8101164

Abstract

Ageing is the result of changes in biochemical and biophysical processes at the cellular level that lead to progressive organ decline. Here we focus on the biophysical changes that impair cellular function of human dermal fibroblasts using donors of increasing age. We find that cell motility is impaired in cells from older donors, which is associated with increased Young’s modulus, viscosity, and adhesion. Cellular morphology also displays parallel increases in spread area and cytoskeletal assembly, with a threefold increase in vimentin filaments alongside a decrease in its remodelling rate. Treatments with withaferin A or acrylamide show that cell motility can be modulated by regulating vimentin assembly. Crucially, decreasing vimentin amount in cells from older individuals to levels displayed by the neonatal donor rescues their motility. Our results suggest that increased vimentin assembly may underlay the aberrant biophysical properties progressively observed at the cellular level in the course of human ageing and propose vimentin as a potential therapeutic target for ageing-related diseases.

Highlights

Ageing is a complex process characterised by temporal changes in biological, biophysical and biochemical function that lead to a progressive whole-body decline throughout the lifespan of an individual
Changes in donor aging have been linked to alterations in cellular morphology [37], and we examined whether the observed aberrations in migration and mechanical properties of human dermal fibroblasts from older donors were associated with changes on their underlying cytoskeleton
Since our results indicated that donor ageing modulated cell biophysical properties and morphology, we investigated whether this was associated with changes in F-actin, tubulin, and the intermediate filament vimentin

Summary

Introduction

Ageing is a complex process characterised by temporal changes in biological, biophysical and biochemical function that lead to a progressive whole-body decline throughout the lifespan of an individual. While age-related deterioration is most conspicuous at the organ level, it has been hypothesised that the underlying causes are likely to be dysfunctions at the cellular and tissue level [1]. Due to the links between pathology and ageing, the majority of ageing research has focused on assessing decline in organ or tissue function and associating it to changes in genetic, epigenetic, or metabolic states. Complex age-associated perturbations at the molecular level may be more captured as aberrations at the cellular level

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