Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

Abstract

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age-related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi-mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro-inflammatory cytokines and extracellular matrixdegrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi-related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non-senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing. K E Y W O R D Scellular senescence, fibroblasts, Golgi apparatus, skin ageing, trans-Golgi network | 923 DESPRES Et al.

A Role for Monosaccharides in Nucleation Inhibition and Transport of Collagen

“…66,86,87 These changes appear to be an unfortunate consequence of aging that arises due to the compromised structure of the Golgi apparatus found in older cells. 83,88 These changes correlate with an imperfect regenerative response, which suggests an underlying mechanism where the insufficient population of GAGs hinders the soluble COL concentration available for repair. Taken together with our monosaccharide findings, the developmental and aging observations motivate future investigations to more fully elucidate the endogenous mechanisms supporting COL tissue regulation in vivo.…”

More than just bricks and mortar: Fibroblasts and ECM in skin health and disease

“…Fibroblast senescence has been a topic of intense research as it intimately links to tissue-level ageing and skin pathologies. [18][19][20][21] This topic is covered in this issue in a research article 22 and a comprehensive review. 23 31,32 and deficient in rats 33 and pigs.…”

Grp94 Inhibitor HCP1 Inhibits Human Dermal Fibroblast Senescence

“…With the wide application of sunscreens and the increasing improvement of sunscreen equipment, the senescence of dermal fibroblasts induced by ultraviolet rays can be largely avoided [ 36 , 37 ]. At the same time, increasing attention is being paid to the senescence of fibroblasts associated with aging, termed replicative senescence [ 38 , 39 ]. Replicative senescence is a phenomenon in which telomeres are shortened due to the continuous division of cells, which induces cell senescence and contributes to organismal aging [ 40 , 41 ].…”