Biology subjects

Dreesen, O.

Publications and source records attributed to Dreesen, O..

4 recordsLinked to original sources

bioRxiv2026

Elimination of senescent cells by mechanical cell competition

Cellular senescence, a hallmark of aging, leads to the accumulation of apoptosis-resistant cells that compromise tissue homeostasis. While senescent cells are known to influence neighboring cells through the senescence-associated secretory phenotype (SASP), the precise nature of the interactions between senescent and normal cells remains elusive. Here we show that progerin-induced senescent cells undergo apoptosis when co-cultured with normal cells. This elimination requires direct cell-cell contact and is mediated by the JNK and p38-MAPK pathways, leading to p53 upregulation and p21 downregulation in progerin-expressing cells. Furthermore, neighboring normal cells exert persistent mechanical compression on progerin-expressing cells prior to their elimination, consistent with mechanical cell competition. In contrast, p16-induced senescent cells resist elimination under the same co-culture conditions, maintaining high p21 levels. Our findings reveal a non-cell-autonomous mechanism for senescent cell clearance, providing new insights into the maintenance of tissue homeostasis during aging.

cell biology↗

bioRxiv2022

ZNF524 directly interacts with telomeric DNA and supports telomere integrity

Telomeres are nucleoprotein structures at the ends of linear chromosomes. In humans, they consist of TTAGGG repeats, which are bound by dedicated proteins such as the shelterin complex. This complex blocks unwanted DNA damage repair at telomeres, e.g. by suppressing non-homologous end joining (NHEJ) through its subunit TRF2. We here describe ZNF524, a zinc finger protein that directly binds telomeric repeats with nanomolar affinity and reveal the base-specific sequence recognition by co-crystallization with telomeric DNA. ZNF524 localizes to telomeres and specifically maintains the presence of the TRF2/RAP1 subcomplex at telomeres without affecting other shelterin members. Loss of ZNF524 concomitantly results in an increase in DNA damage signaling and recombination events. Overall, ZNF524 is a direct telomere-binding protein involved in the maintenance of telomere integrity.

cell biology↗

bioRxiv2022

Inflammaging in human photoexposed skin: Early onset of senescence and imbalanced epidermal homeostasis across the decades.

Inflammaging is a theory of aging which purports that low-level chronic inflammation leads to cellular dysfunction and premature aging of surrounding tissue. Skin is susceptible to inflammaging because it is the first line of defense from the environment, particularly solar radiation. To better understand the impact of aging and photoexposure on epidermal biology we performed a systems biology-based analysis of photoexposed face and arm and photoprotected buttock sites from women between the ages of 20s to 70s. Biopsies were analyzed by histology, transcriptomics, and proteomics and skin surface biomarkers collected from tape strips. We identified morphological changes with age of epidermal thinning, rete ridge pathlength loss, and stratum corneum thickening. The SASP biomarkers IL-8 and IL-1RA/IL1- were consistently elevated in face across age and cis/trans-urocanic acid were elevated in arms and face with age. In older arms, the DNA damage response biomarker 53BP1 showed higher puncti numbers in basal layers and epigenetic aging was accelerated. Genes associated with differentiation and senescence show increasing expression in the 30s whereas genes associated with hypoxia and glycolysis increase in the 50s. Proteomics comparing 60s vs 20s confirmed elevated levels of differentiation and glycolytic related proteins. Representative immunostaining for proteins of differentiation, senescence, and oxygen sensing/hypoxia shows similar relationships. This systems biology-based analysis provides a body of evidence that young photoexposed skin is undergoing inflammaging. We propose the presence of chronic inflammation in young skin contributes to an imbalance of epidermal homeostasis that leads to a prematurely aged appearance during later life.

systems biology↗

bioRxiv2019

p53 induces senescence in the unstable progeny of aneuploid cells

Aneuploidy is the condition of having an imbalanced karyotype, which is strongly associated with tumor initiation, evolution, and acquisition of drug-resistant features, possibly by generating heterogeneous populations of cells with distinct genotypes and phenotypes. Multicellular eukaryotes have therefore evolved a range of extrinsic and cell-autonomous mechanisms for restraining proliferation of aneuploid cells, including activation of the tumor suppressor protein p53. However, accumulating evidence indicates that a subset of aneuploid cells can escape p53-mediated growth restriction and continue proliferating in vitro. Here we show that such aneuploid cell lines display a robust modal karyotype and low frequency of chromosomal aberrations despite ongoing chromosome instability. Indeed, while these aneuploid cells are able to survive for extended periods in vitro, their chromosomally unstable progeny remain subject to p53-induced senescence and growth restriction, leading to subsequent elimination from the aneuploid pool. This mechanism helps maintain low levels of heterogeneity in aneuploid populations and may prevent detrimental evolutionary processes such as cancer progression and development of drug resistance.

cancer biology↗