A new study on senescent cells has discovered new findings of its emerging role in pathophysiology and tissue homeostasis.
In This Article:
Senescent Cells – Its Benefits and Effects
What Is Senescent?
Normal cells become senescent after a certain number of successive divisions or after being exposed to genotoxic stresses, marked by a lasting growth arrest. Furthermore, they secrete higher levels of pro-inflammatory and catabolic mediators, which is referred to as the “senescence-associated secretory phenotype.” Additionally, senescent cells show altered expression and organization of several extracellular matrix elements, resulting in complex microenvironment remodeling.
Cellular senescence is a permanent growth arrest that is thought to be essential in tumor suppression. In physiological conditions, cellular senescence can play an essential role in tumor suppression, wound healing, and tissue fibrosis defense. This particular secretion phenotype of senescent cells may significantly impact physiological and pathological outcomes in species.
Beneficial Effects of Cellular Senescence
1 Wound Healing
Cellular senescence is also necessary for skin wound healing. Fibroblasts are mobilized to the site of the injury and differentiate into myofibroblasts, which are advanced contractile fibroblasts that deposit extracellular matrices for healing.
At the end of wound healing, the matricellular protein CCN1, which is abundant in affected regions, attaches to its receptor, integrin 61, and stimulates oxidative stress formation in myofibroblasts.
2 Developmentally Programmed Senescence
Other findings show that cellular senescence develops during development and that senescent cells are most likely involved in facilitating tissue remodeling during development. Research on mice found that senescent cells were found in the mouse embryo, including the mesonephros, apical ectodermal ridge, neural roof plate, and inner ear endolymphatic sac. These senescent cells are crucial for organ development and tissue growth during development.
3 Tumor Suppression
Regular cells enter senescence after a typical number of divisions, while tumor-derived or virally mutated cells proliferate indefinitely in culture. Genetic experiments using cell fusion technology, which fused normal human cells with different immortal cell lines, revealed that the resultant hybrids did not multiply forever.
This finding suggested that the senescent phenotype is common and that immortal cells emerge as a result of mutations in genes or pathways involved in growth arrest in order to avoid cellular senescence. This was the first proof that cell senescence played a part in tumor suppression.
There is mounting evidence that cellular senescence acts as a deterrent against transformation and inhibits precancerous cell proliferation in vivo. Senescent cells in premalignant tumors can be detected in vivo because they are positive for SA-β-gal and express p16.
4 Cardiac Fibrosis
In a mouse model, cellular senescence also plays a vital role in controlling cardiac fibrosis after a myocardial infarction (MI). One week after MI, senescent cardiac fibroblasts accumulated in infarcted hearts in wild-type mice. This was followed by an increase in the activity of the senescence markers p53, p16, and p21, as well as SA-β-gal
Notably, in p53-deficient mice, the aggregation of senescent fibroblasts, macrophage penetration, and MMPs such as MMP2 and MMP9 were significantly reduced; however, collagen deposition was increased after MI. This finding suggested that p53-mediated cellular senescence is essential for limiting cardiac collagen deposition and fibrosis.
5 Liver Fibrosis
Liver fibrosis develops as a result of an overabundance of extracellular matrix proteins, such as collagen. Cirrhosis and liver failure may occur as a result of advanced liver fibrosis. It has been documented that the senescence program plays a role in acute liver injury caused in vivo by a liver-damaging agent (CCl4).
Damage activates hepatic stellate cells, which continue to generate extracellular matrix components in order to repair the damage. After that, the stellate cells become senescent and secrete SASP factors, like MMPs, to restore the fibrotic scar.
SASP, linked to stellate cell senescence, attracts immune cells, and senescent stellate cells are cleared by attracted natural killer cells. As a result, it is assumed that cellular senescence is essential for regulating tissue repair and maintaining organ integrity.
Cellular senescence is a state of basically permanent growth arrest that has been proposed as an antitumor mechanism. Senescent cells secrete a plethora of pro-inflammatory factors through SASP, in addition to growth arrest. There is now a lot of evidence that the SASP of senescent cells plays a role in the pathogenesis of age-related diseases.
It has been proposed that the aggregation of senescent cells in tissues speeds up tissue remodeling caused by SASP causes, decreases tissue integrity and function, and leads to organismal aging. Indeed, senescent cells can be present in various tissues under pathological conditions or in advanced aging.
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