Cellular senescence is a stress response triggered by multiple mechanisms including telomere attrition, oncogene activation or oncosuppressor deregulation. Activation of Mitogen-Activated Protein Kinases (MAPK) is widely involved in triggering cellular senescence, a state of stable growth arrest, that leads to a profound remodulation of cell cycle, metabolism as well as to the activation of numerous soluble factors, collectively named as senescence-associated secretory phenotype (SASP). Additionally, MAPKs together with their upstream activators and downstream effectors are invariably implicated in physiological and pathological processes, including aging, age-related diseases as well as cancer. With regards to cancer, the senescence response is widely recognized as a potent tumor suppressive and immuno-stimulatory mechanism so that pro-senesce drugs are actively sought after. However, several lines of evidence indicate that cellular senescence also drives undesirable effects that sustain and promote cancer growth, metastasis and tumor immune evasion. Taking all these into consideration, studies directed to eradicate senescent cells using senolytic compounds or to reprogram SASP by senomorphic agents may provide additional opportunities for cancer therapy. Furthermore, modulation of cellular senescence may well be relevant to decelerate aging by improving regeneration. In this respect, both senolytic as well as senomorphic agents are currently studied to potentially extend healthspan and lifespan. Another interesting aspect in current pandemic times is that senescence has emerged as a valuable target against SARS-CoV-2 and, possibly, other viral infections. Thus, identifying a possible gene signature induced by viral infection and that modulates SASP may provide additional therapeutical approaches either to prevent viral infection or to reduce damaging effects of a subsequent inflammation.
In this Research Topic, we aim to
(i) highlight the contribution of all MAPKs, both conventional and atypical, as well as their upstream activators or downstream targets in cellular senescence
(ii) outline how to target these kinases in order to effectively reduce cancer growth and spreading, and
(iii) to ameliorate aging and age-related diseases as well as other pathological states by interfering with cellular senescence
Cellular senescence is a stress response triggered by multiple mechanisms including telomere attrition, oncogene activation or oncosuppressor deregulation. Activation of Mitogen-Activated Protein Kinases (MAPK) is widely involved in triggering cellular senescence, a state of stable growth arrest, that leads to a profound remodulation of cell cycle, metabolism as well as to the activation of numerous soluble factors, collectively named as senescence-associated secretory phenotype (SASP). Additionally, MAPKs together with their upstream activators and downstream effectors are invariably implicated in physiological and pathological processes, including aging, age-related diseases as well as cancer. With regards to cancer, the senescence response is widely recognized as a potent tumor suppressive and immuno-stimulatory mechanism so that pro-senesce drugs are actively sought after. However, several lines of evidence indicate that cellular senescence also drives undesirable effects that sustain and promote cancer growth, metastasis and tumor immune evasion. Taking all these into consideration, studies directed to eradicate senescent cells using senolytic compounds or to reprogram SASP by senomorphic agents may provide additional opportunities for cancer therapy. Furthermore, modulation of cellular senescence may well be relevant to decelerate aging by improving regeneration. In this respect, both senolytic as well as senomorphic agents are currently studied to potentially extend healthspan and lifespan. Another interesting aspect in current pandemic times is that senescence has emerged as a valuable target against SARS-CoV-2 and, possibly, other viral infections. Thus, identifying a possible gene signature induced by viral infection and that modulates SASP may provide additional therapeutical approaches either to prevent viral infection or to reduce damaging effects of a subsequent inflammation.
In this Research Topic, we aim to
(i) highlight the contribution of all MAPKs, both conventional and atypical, as well as their upstream activators or downstream targets in cellular senescence
(ii) outline how to target these kinases in order to effectively reduce cancer growth and spreading, and
(iii) to ameliorate aging and age-related diseases as well as other pathological states by interfering with cellular senescence