Abstract:
:The aging proteostasis decline manifests in a failure of aging cells and organisms to properly respond to proteotoxic challenges. This proteostasis collapse has long been considered a hallmark of aging in nematodes, and has recently been shown to occur also in human cells upon entry to senescence, opening the way to exploring the phenomenon in the broader context of human aging. Cellular senescence is part of the normal human physiology of aging, with senescent cell accumulation as a prominent feature of aged tissues. Being highly resistant to cell death, senescent cells, as they accumulate, become pro-inflammatory and promote disease. Here we discuss the causes of human senescence proteostasis decline, in view of the current literature on nematodes, on the one hand, and senescence, on the other hand. We review two major aspects of the phenomenon: (1) the decline in transcriptional activation of stress-response pathways, and (2) impairments in proteasome function. We further outline potential underlying mechanisms of transcriptional proteostasis decline, focusing on reduced chromatin dynamics and compromised nuclear integrity. Finally, we discuss potential strategies for reinforcing proteostasis as a means to improve organismal health and address the relationship to senolytics.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Meller A,Shalgi Rdoi
10.1016/j.yexcr.2021.112474subject
Has Abstractpub_date
2021-01-09 00:00:00pages
112474issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(21)00005-7journal_volume
399pub_type
杂志文章abstract::The specific activities of pyruvate kinase and phosphofructokinase but not lactate dehydrogenase increase as P-815 mastocytoma cells approach the stationary phase. During this growth period, the rates of uptake of labelled precursors into DNA, RNA and total protein decreases. On the other hand, the pyruvate kinase pro...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(83)90367-1
更新日期:1983-12-01 00:00:00
abstract::Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-line...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2008.01.009
更新日期:2008-04-01 00:00:00
abstract::Autosomal dominantly inherited missense mutations in lamins A and C cause familial partial lipodystrophy of the Dunnigan-type (FPLD), and myopathies including Emery-Dreifuss muscular dystrophy (EDMD). While mutations responsible for FPLD are restricted to the carboxyl-terminal tails, those responsible for EDMD are spr...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2002.5669
更新日期:2003-01-01 00:00:00
abstract::The purpose of the present study was to determine if hemodynamic shear stress increases free cytosolic Ca2+ concentration ([Ca2+]i) of cultured pulmonary artery endothelial cells exposed to steady laminar fluid flow in a parallel plate chamber. Average [Ca2+]i was estimated by measuring cell-associated fura-2 fluoresc...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(92)90145-x
更新日期:1992-01-01 00:00:00
abstract::The rheumatic diseases are characterized by the production of autoantibodies that are usually directed against components of the cell nucleus. In this communication, we describe autoantibodies that recognize DNA topoisomerase II (anti-topoII) present in the serum of a patient with systemic lupus erythematosus. Several...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(89)90067-0
更新日期:1989-02-01 00:00:00
abstract::Insulin mimetics, including zinc containing compounds, have previously been shown to influence chondrogenesis as it relates to healing of fractures in various preclinical models. However, the mechanism by which these compounds drive chondrogenic differentiation is yet undefined. Here, via next-generation sequencing (N...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2020.112436
更新日期:2021-01-21 00:00:00
abstract::Gp38k is a 383-amino-acid secreted glycoprotein expressed by cultured vascular smooth muscle cells during the time of transition from a proliferating monolayer culture to a nonproliferating multilayered (differentiated) culture. Expression continues as the cell culture forms multicellular nodules. Because this transit...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1999.4511
更新日期:1999-07-10 00:00:00
abstract::Specific mitochondrial incorporation of 10 N-nonyl acridine orange (NAO) is demonstrated by subcellular fractionation of rat hepatocytes. Moreover, comparative studies with NAO and rhodamine 123 (Rh 123) prove that acridine orange-derivative uptake is independent of transmembrane mitochondrial potential, a property al...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(90)90219-z
更新日期:1990-01-01 00:00:00
abstract::The scavenger receptor (SR-A) is considered to play a role in host defense by scavenging endotoxins, oxidized proteins, and denatured or otherwise modified self components, which are routed toward degradation in macrophages. Recent data suggest that SR-A also functions as an adhesion molecule. Our previous finding of ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1997.3876
更新日期:1998-02-25 00:00:00
abstract::Hyperglycemia and hyperlipidemia (glycolipotoxicity)-triggered islet β-cell dysfunction is known to drive the progression of obesity-related type 2 diabetes, however the underlying mechanisms have not been clearly elucidated. The current study aimed to investigate the role of mitogen-activated protein kinase phosphata...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2019.06.012
更新日期:2019-09-01 00:00:00
abstract::dNTP pools are quite low in immature oocytes of the starfish, expand during the 1-methyladenine-induced maturational process and thereafter reach a maximal level (approx. 35, 20, 15 and 5 fmoles/egg for dTTP, dCTP, dATP and dGTP, respectively) which is maintained in overmatured eggs. Maturing oocytes were inseminated ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/s0014-4827(83)80023-8
更新日期:1983-04-15 00:00:00
abstract::Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2010.07.003
更新日期:2010-12-10 00:00:00
abstract::The low density lipoprotein receptor-related protein (LRP) binds multiple, distinct ligands and participates in constitutive endocytosis and signal transduction. Using an in vitro reconstitution system and a new biochemical complementation assay, we have explored the limiting cytosolic requirements for endocytosis of ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2005.12.022
更新日期:2006-05-01 00:00:00
abstract::We have studied the effects of the phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the contractility, locomotion, morphology, and adhesion of two mammalian fibroblastic cell lines. Using the silicone rubber substratum technique, we have found that the first observable response to the tumor ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(88)90024-9
更新日期:1988-07-01 00:00:00
abstract::Ets variant gene 5 (ETV5) and glial cell-derived neurotrophic factor (GDNF) are produced in Sertoli cells and required for maintenance and self-renewal of spermatogonial stem cells (SSCs) in mice. Fibroblast growth factors (FGFs) have been reported to stimulate Etv5 mRNA expression, and FSH was shown to stimulate Gdnf...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2007.05.002
更新日期:2007-08-15 00:00:00
abstract::Tetracyclines have long been used as valuable broad-spectrum antibiotics. The high antibacterial activity of tetracyclines, combined with their good tolerability, has led to their widespread use in treating various infectious diseases. However, similar to other antibiotics, tetracyclines are also known for their adver...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2013.11.012
更新日期:2014-01-15 00:00:00
abstract::Members of the Bcl-2 family of proteins are key regulators of apoptosis. Some of these proteins undergo posttranslational modification, such as phosphorylation or proteolysis, that serves to alter their function. Caspases are known to cleave Bid, a proapoptotic family member, as well as Bcl-2 and Bcl-X(L), two prosurv...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2000.4859
更新日期:2000-05-01 00:00:00
abstract::Actions of transforming growth factor-β are largely context dependent. For instance, TGF-β is growth inhibitory to epithelial cells and many tumor cell-lines while it stimulates the growth of mesenchymal cells. TGF-β also activates fibroblast cells to a myofibroblastic phenotype. In order to understand how the respons...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2015.03.001
更新日期:2015-06-10 00:00:00
abstract::We developed an improved method for isolation of peroxisome biogenesis-defective somatic animal cell mutants, using a combination of green fluorescent protein (GFP) expression and the 9-(1'-pyrene)nonanol/ultraviolet (P9OH/UV) selection method. We used TKaG1 and TKaG2 cells, the wild-type Chinese hamster ovary (CHO) c...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1999.4413
更新日期:1999-05-01 00:00:00
abstract::The rate-limiting step in melanogenesis is catalyzed by tyrosinase, a multifunctional enzyme encoded by the albino locus. We have previously reported that depletion of protein kinase C by long-term treatment of B16 mouse melanoma cells with phorbol dibutyrate (PDBu) prevented cell density-dependent melanogenesis. This...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1997.3773
更新日期:1997-11-25 00:00:00
abstract::Previous studies have shown that calpains are autolytically cleaved during the disease process of mdx dystrophy, a mouse model for Duchenne muscular dystrophy, indicating that calpains may be activated and play a role in proteolysis that occurs in muscular dystrophy (J. Biol. Chem. 270(18), 10909-10914, 1995). In the ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1996.0227
更新日期:1996-08-01 00:00:00
abstract::Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby mali...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2012.12.027
更新日期:2013-03-10 00:00:00
abstract::The stroma, the middle layer of the cornea, is a connective tissue making up most of the corneal thickness. The stromal extracellular matrix (ECM) consists of highly organised lamellae which are made up of tightly packed fibrils primarily composed of collagens type I and V. This layer is interspersed with keratocytes,...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2016.08.010
更新日期:2016-09-10 00:00:00
abstract::Matrix metalloproteinases (MMPs) play a key role in cellular invasion and growth. Recent observations on tumor tissue samples suggest that MMP activity is altered in relation to cell density. Therefore, we examined MMP(-1,-2,-3,-8,-9,-10,-11 and -13) and TIMP-1/-2 expression of well-defined cell densities in breast ca...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2004.12.019
更新日期:2005-04-15 00:00:00
abstract::The neurohormone serotonin (5HT) triggers meiosis reinitiation in oocytes of the pelecypod molluscs Spisula solidissima and Ruditapes philippinarum. However, while Spisula oocytes complete maturation, Ruditapes oocytes arrest in metaphase I. Anti-phosphotyrosine antibody revealed that serotonin triggered an early tyro...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1994.1163
更新日期:1994-06-01 00:00:00
abstract::Laminins assemble into trimers composed of alpha, beta, and gamma chains which posttranslationally are glycosylated and sometimes proteolytically cleaved. In the current paper we set out to characterize posttranslational modifications and the laminin isoforms formed by laminin alpha1 and alpha5 chains. Comparative pul...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2000.4980
更新日期:2000-09-15 00:00:00
abstract::Using the restriction enzymes MspI and HpaII in the nick translation procedure it has been shown that decondensation of the paracentric heterochromatin of chromosome 9 during human spermatogenesis is associated with hypomethylation of the DNA sequences in this domain. Somatic cells treated with 5'-azacytidine also sho...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(92)90421-4
更新日期:1992-09-01 00:00:00
abstract::Wnt1 and -5a have been shown to modulate the proliferation and differentiation of midbrain dopaminergic (DA) neurons. However, it is not known whether other Wnts or which Frizzled (Fz) receptors are expressed in the developing midbrain. We found that 13 out of 19 Wnts, all 10 Fzs, and several intracellular Wnt signali...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2006.01.032
更新日期:2006-05-15 00:00:00
abstract::Interference of colchicine with meiotic chromosome pairing in the wild garlic, Allium ursinum, was studied using a whole-mount spreading technique for synaptonemal complexes. Colchicine was found to cause (i) pairing suppression (arrest of leptotene) and (ii) deficient pairing initiation at zygotene in connection with...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(88)90381-3
更新日期:1988-09-01 00:00:00
abstract::Lithium has been found to be a novel inhibitor of the terminal differentiation of Friend murine erythroleukemia cells. A general method for the quantitative analysis of differentiation inhibitors has been developed and used to compare the site of inhibition by lithium with that by vanadate. Lithium inhibits the commit...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(87)90012-7
更新日期:1987-02-01 00:00:00