CELLULAR SENESCENCE

Cellular senescence, including replicative senescence (RS) and stress-induced premature senescence (SIPS), constitute a permanent state of cell cycle arrest that occurs in proliferating cells subjected to different stresses.

This irreversible proliferative arrest process is associated with changes in chromatin organization, gene transcription, and protein secretion either in vitro or in vivo ^(1,2,3). The senescent cells are characterized by: prolonged cell cycle arrest, transcriptional changes, acquisition of a bioactive secretome, known as the senescence-associated secretory phenotype (SASP), macromolecular damage, and deregulated metabolism ⁽⁴⁾.

Cellular senescence-Pathways to cellular senescence in eukaryotic cells.

Pathways to cellular senescence in eukaryotic cells. Multiple discrete cellular insults act via distinct signaling mechanisms to induce cell-cycle arrest in the kidney at either the G1/S (via inhibition of cdk2 and/or cdk4/6) or G2/M checkpoints (via Chk1/2 activation or cdc2/25c inhibition). Inactivation of oncogenes and spindle/epigenetic/nucleolar stress trigger activation of the cyclin-dependent kinase inhibitor p16ink4a. Telomere shortening, DNA damage, mitogen or oncogene activation, and hypoxia/reoxygenation also result in G1/S cell-cycle arrest, via a pathway dependent on p53 and p21cip1 activation. In contrast to this, developmental senescence appears to induce p21cip1 by pathways mediated by TGFb/PI3K and independent of p53. ATM/ATR/ARF, Ataxia–Telangiectasia Mutated/Ataxia Telangiectasia and Rad3-related protein/p14 Alternate Reading Frame (human).⁽²⁾

Senescence is a cellular defense mechanism that prevents the cells to acquire an unnecessary damage. The senescent state is accompanied by a failure to re-enter the cell cycle in response to mitogenic stimuli, an enhanced secretory phenotype and resistance to cell death ⁽¹⁾.

WHAT ARE THE CAUSES OF CELL SENESCENCE?

The senescence program can be activated in normal, pre-neoplastic, and malignant cells in response to a wide variety of stimuli like injury, normal organogenesis, tissue homeostasis and repair, DNA damage or critical telomere shortening leading to exposure of DNA ends, oncogenic mutations, metabolic stress, mitochondrial dysfunction, inflammatory cytokines/chemokines and damage signals (e.g., protein misfolding, autophagy disruption), cancer, and aging ^(1,2,4).
The establishment and maintenance of all cell senescence phenotypes are influenced and closely linked to inhibition of the cell cycle machinery ⁽⁴⁾.

Cellular senescence-Potential causes and consequences of cell senescence

Potential causes and consequences of cell senescence. Several factors have been identified to induce cell senescence, including telomere shortening, oncogene activation, DNA damage,and oxidative stress. Senescent cells, on the other hand,exhibit multiple characteristics, including growth arrest, metabolic changes, altered apoptosis sensitivity, and senescence-associated secretary phenotype (SASP) ⁽³⁾ .

Due to the multiplicity of stress signals and effector pathways involved in its execution, senescence is associated with various phenotypes the characteristics of which depend on the signals that induced senescence, the originating cell type, the time elapsed since senescence initiation, and the site where senescent cells are located⁽⁴⁾.

CELLULAR SENESCENCE AND DISEASES

Senescence is one of the causative processes of various pathologies like kidney disease, aging and aging-related disorders including Alzheimer’s disease, diabetes and associated diabetic complications, cardiovascular disease, fatty liver disease ^(1,2,3,5).

Besides its pathological role, senescent cells can also play a positive role. In embryogenesis and tissue remodeling, senescent cells are necessary for the proper development of the embryo and tissue repair. In cancer, senescence acts as a powerful barrier to prevent tumorigenesis ⁽¹⁾.

(1) Calcinotto A, et al. Cellular Senescence: Aging, Cancer, and Injury. Physiol Rev. (2019);99(2):1047-1078.

(2) Docherty MH, et al. Cellular Senescence in the Kidney. J Am Soc Nephrol. (2019);30(5):726-736.

(3) Liu RM. Aging, Cellular Senescence, and Alzheimer's Disease. Int J Mol Sci. (2022);23(4):1989.

(4) Roger L, Tomas F, Gire V. Mechanisms and Regulation of Cellular Senescence. Int J Mol Sci. (2021);22(23):13173.

(5) Palmer AK, et al. Cellular senescence: at the nexus between ageing and diabetes. Diabetologia. (2019) ;62(10):1835-1841.

CELLULAR SENESCENCE SIGNALING PATHWAY BIOMARKER LIST

You can custom your own SignArrays® with the genes of interest of your choice, according to your project, you just have to download and complete our Personalized SignArrays® information file and send it at [email protected]

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human signaling pathways

Signaling Pathways	Product ref	Informations
Cellular Senescence	CS1H1	List infos

Species : Mus musculus (mouse)

Mouse signaling pathways

Signaling Pathways	Product ref	Informations
Cellular Senescence	CS1M1	List infos

Species : Rattus norvegicus (rat)

Rat signaling pathways

Signaling Pathways	Product ref	Informations
Cellular Senescence	*******	List In progress...

Species : Sus Scrofa (Pig)

Pig signaling pathways

Signaling Pathways	Product ref	Informations
Cellular Senescence	*******	List In progress...

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