Abstract
As the world’s population progressively ages, the burden on the socio-economic and health systems is escalating, demanding sustainable and lasting solutions. Cellular senescence, one of the hallmarks of ageing, is a state of irreversible cell cycle arrest that occurs in response to various genotoxic stressors and is considered an important factor in the development of many age-related diseases and therefore a potential therapeutic target. Here, the role of senescent cells in age-related diseases is discussed, focusing on their formation and main characteristics. The mechanisms leading to senescent cells are presented, including replicative and premature senescence as well as senescence that occurs in various physiological processes, such as wound healing. The second part comprises a comprehensive description of various biomarkers currently used for the detection of senescent cells along with the investigated therapeutic approaches, namely senolytics, senomorphics and the clearance of senescent cells by the immune system. Potential delivery systems suitable for such therapies and model organisms to study senescence are also briefly examined. This in-depth overview of cellular senescence contributes to a deeper understanding of a rapidly evolving area aimed to tackle the age-related diseases in a more mechanistic way, as well as highlights future research opportunities.
【저자키워드】 interleukin, reactive oxygen species, DNA damage response, heat shock protein, mitogen-activated protein kinase, ILInterleukin, MAPKmitogen-activated protein kinase, PTENphosphatase and tensin homolog, phosphatase and tensin homolog, ROSreactive oxygen species, SASPsenescence-associated secretory phenotype, senescence-associated secretory phenotype, ERKextracellular signal-regulated kinases, extracellular signal-regulated kinases, AKTProtein kinase B, also known as Akt, Protein kinase B, ATMAtaxia-telangiectasia mutated, Ataxia-telangiectasia mutated, ATRAtaxia telangiectasia and Rad3-related protein, Ataxia telangiectasia and Rad3-related protein, BclAnti-apoptotic B-cell lymphoma, Anti-apoptotic B-cell lymphoma, Chk2Checkpoint kinase 2, Checkpoint kinase 2, DDRDNA damage response, DNA-SACRSDNA segments with chromatin alterations reinforcing senescence, DNA segments with chromatin alterations reinforcing senescence, FOXO4Forkhead box protein O4, Forkhead box protein O4, HSP90Heat shock protein, IkBInhibitor of nuclear factor kappa B, Inhibitor of nuclear factor kappa B, IKKIκB kinase, IκB kinase, IMMP2LInner mitochondrial membrane peptidase subunit 2, Inner mitochondrial membrane peptidase subunit 2, IRAK1Interleukin-1 receptor-associated kinase 1, Interleukin-1 receptor-associated kinase 1, MDM2Mouse double minute 2 homolog, also known as E3 ubiquitin-protein ligase Mdm2, Mouse double minute 2 homolog, MK2Mitogen-activated protein kinase-activated protein kinase 2, Mitogen-activated protein kinase-activated protein kinase 2, mTORC1/2Mammalian target of rapamycin complex 1/2, Mammalian target of rapamycin complex 1/2, NADPHNicotinamide adenine dinucleotide phosphate, Nicotinamide adenine dinucleotide phosphate, NEMONF-kappa-B essential modulator, NF-kappa-B essential modulator, NF-kBNuclear factor – κB, Nuclear factor – κB, NKG2AAn activating Natural Killer (NK) cell receptor, group 2A, An activating Natural Killer (NK) cell receptor, NKG2DAn activating Natural Killer (NK) cell receptor, group 2D, OISOncogene-induced senescence, Oncogene-induced senescence, PI3KPhosphoinositide 3-kinases, Phosphoinositide 3-kinases, PICSPTEN-loss–induced cellular senescence, PTEN-loss–induced cellular senescence, (p)Rb(phosphorylated) retinoblastoma protein, (phosphorylated) retinoblastoma protein, SAHFSenescence-associated heterochromatin foci, Senescence-associated heterochromatin foci, SAMSenescence-accelerated mice, Senescence-accelerated mice, SA-β-GalSenescence-associated beta-galactosidase, Senescence-associated beta-galactosidase, SIRT1Sirtuin 1, Sirtuin 1, TISTherapy induced senescence, Therapy induced senescence, 【초록키워드】 therapy, Biomarker, immune system, Characteristics, Research, Premature, health system, disease, mechanism, cellular senescence, physiological, Stressor, therapeutic approaches, organism, wound healing, hallmark, clearance, potential therapeutic target, cell cycle arrest, highlight, genotoxic, examined, investigated, contribute, occur, replicative, Potential, senescent cell, 【제목키워드】 target, disease, Cell,