Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases.
Reads0
Chats0
TLDR
The functional and regulatory network of SASPs toward opening up new possibilities for controlling aging and aging‐associated diseases are discussed.Abstract:
'Cellular senescence' is a state in which cells undergo irreversible cell cycle arrest in response to a variety of cellular stresses. Once cells senesce, they are strongly resistant to any mitogens, including oncogenic stimuli. Therefore, cellular senescence has been assumed to be a potent anticancer mechanism. Although irreversible cell-cycle arrest is traditionally considered the major characteristic of senescent cells, recent studies have revealed some additional functions. Most noteworthy is the increased secretion of various secretory proteins, such as inflammatory cytokines, chemokines, growth factors, and matrix metalloproteinases, into the surrounding extracellular fluid. These newly recognized senescent phenotypes, termed senescence-associated secretory phenotypes (SASPs), reportedly contribute to tumor suppression, wound healing, embryonic development, and even tumorigenesis promotion. Thus, SASPs appear to be beneficial or deleterious, depending on the biological context. Since senescent cells are known to accumulate during the aging process in vivo, it is quite possible that their accumulation in aged tissues promotes age-associated functional decline and various diseases, including cancers, at least to some extent. Here, we focus on and discuss the functional and regulatory network of SASPs toward opening up new possibilities for controlling aging and aging-associated diseases. This article is protected by copyright. All rights reserved.read more
Citations
More filters
Journal ArticleDOI
Nociceptive transient receptor potential canonical 7 (TRPC7) mediates aging-associated tumorigenesis induced by ultraviolet B
Wen‐Li Hsu,Wen‐Li Hsu,Wen‐Li Hsu,Ming-Hsien Tsai,Ching-Ying Wu,Jui-Lin Liang,Jian-He Lu,Jennifer S. Kahle,Hsin-Su Yu,Chia-Jung Yen,Chia-Jung Yen,Chen Tung Yen,Yi‐Chun Hsieh,Yung‐Yun Huang,Li‐Ching Lin,Tsung‐Fu Tsai,Chu-Huang Chen,Tohru Yoshioka +17 more
TL;DR: The findings support that TRPC7 is a potential tumor initiator gene and that it causes cell aging and genomic instability, followed by a change in the activity of proto‐oncogenes and tumor suppressor genes to promote tumorigenesis.
Journal ArticleDOI
An evolutionary transcriptomics approach links CD36 to membrane remodeling in replicative senescence
Marie Saitou,Darleny Y. Lizardo,Recep Ozgur Taskent,Alec Millner,Omer Gokcumen,Gunes Ekin Atilla-Gokcumen +5 more
TL;DR: Comparison RNAseq experiments to detect genes associated with replicative senescence in two different human fibroblast cell lines and at different time points identified 841 and 900 genes that are significantly up- and downregulated in senescent cells, respectively, in both cell lines.
Journal ArticleDOI
Alteration of Hypoxia-Associated Gene Expression in Replicatively Senescent Mesenchymal Stromal Cells under Physiological Oxygen Level.
TL;DR: The results show that significant reduction of proliferative activity of MSCs is observed after 20 passages, and genes ANGPTL4, GYS1, PKM2, SERPINE1, and TP53 were downregulated under hypoxia, which is known to lead to attenuation of some morphological and functional changes associated with aging.
Journal ArticleDOI
Endothelial senescence-associated secretory phenotype (SASP) is regulated by Makorin-1 ubiquitin E3 ligase.
Sivareddy Kotla,Nhat Tu Le,Hang Thi Vu,Kyung Ae Ko,Young Jin Gi,Tamlyn N. Thomas,Carolyn J. Giancursio,Aldos J. Lusis,John P. Cooke,Keigi Fujiwara,Jun Ichi Abe +10 more
TL;DR: TERF2IP S205 phosphorylation, a downstream event of p90RSK activation, uniquely inhibits MKRN1 expression and contributes to EC activation and senescence, which are key events for atherogenesis.
References
More filters
Journal ArticleDOI
The serial cultivation of human diploid cell strains.
Leonard Hayflick,P.S. Moorhead +1 more
TL;DR: A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level.
Journal ArticleDOI
A biomarker that identifies senescent human cells in culture and in aging skin in vivo
Goberdhan P. Dimri,X Lee,G Basile,Meileen Acosta,G Scott,C Roskelley,E E Medrano,Maarten H.K. Linskens,Ivica Rubelj,Olivia M. Pereira-Smith +9 more
TL;DR: It is shown that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture, which provides in situ evidence that senescent cells may exist and accumulate with age in vivo.
Journal ArticleDOI
The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
Journal ArticleDOI
Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
Journal ArticleDOI
Myofibroblasts and mechano-regulation of connective tissue remodelling
TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.