Cellular senescence, an irreversible state of cell cycle arrest characterized by phenotypic changes and a specific secretory profile, plays a dual role in liver health and disease. Under physiological conditions, senescence aids organ repair and regeneration, but its accumulation due to aging or pathological stress significantly contributes to chronic liver diseases, including alcoholic liver disease, metabolic dysfunction-associated steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Senescence is identified by a range of cellular and molecular changes, such as morphological alterations, expression of cell cycle inhibitors, senescence-associated β-galactosidase activity, and nuclear membrane changes. The onset of senescence in organ cells can affect the entire organism, primarily through the senescence-associated secretory phenotype, which has autocrine, paracrine, and endocrine effects on tissue microenvironments. The objective of this review is to offer a contemporary overview of the pathophysiological events involving hepatic senescent cells and to elucidate their role in the onset and progression of liver diseases, particularly through mechanisms like telomere shortening, genomic and mitochondrial DNA damage, and inflammation. Additionally, this review discusses the emerging senolytic therapies aimed at targeting senescent cells to delay or mitigate liver disease progression. The therapeutic potential of these interventions, alongside their safety and effectiveness, highlights the need for further research to refine these approaches and address unresolved problems in the field of hepatic cellular senescence.
Humans ; Cellular Senescence/physiology* ; Liver Diseases ; Animals ; DNA Damage ; Telomere Shortening/physiology*

Alzheimer's disease (AD) is the most common cause of age-related dementia. The neuropathological hallmarks of AD include extracellular deposition of amyloid-beta peptides and neurofibrillary tangles that lead to intracellular hyperphosphorylated tau in the brain. Soluble amyloid-beta oligomers are the primary pathogenic factor leading to cognitive impairment in AD. Neural stem cells (NSCs) are able to self-renew and give rise to multiple neural cell lineages in both developing and adult central nervous systems. To explore the relationship between AD-related pathology and the behaviors of NSCs that enable neuroregeneration, a number of studies have used animal and in vitro models to investigate the role of amyloid-beta on NSCs derived from various brain regions at different developmental stages. However, the Abeta effects on NSCs remain poorly understood because of conflicting results. To investigate the effects of amyloid-beta oligomers on human NSCs, we established amyloid precursor protein Swedish mutant-expressing cells and identified cell-derived amyloid-beta oligomers in the culture media. Human NSCs were isolated from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres. Human NSCs exposure to cell-derived amyloid-beta oligomers decreased dividing potential resulting from senescence through telomere attrition, impaired neurogenesis and promoted gliogenesis, and attenuated mobility. These amyloid-beta oligomers modulated the proliferation, differentiation and migration patterns of human NSCs via a glycogen synthase kinase-3beta-mediated signaling pathway. These findings contribute to the development of human NSC-based therapy for AD by elucidating the effects of Abeta oligomers on human NSCs.
Amyloid beta-Peptides/*pharmacology ; Animals ; Apoptosis ; Cell Aging ; Cell Movement ; Cell Proliferation ; Culture Media, Conditioned/chemistry/pharmacology ; Fetus/cytology ; Glycogen Synthase Kinase 3/*metabolism ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/*drug effects/metabolism/physiology ; Signal Transduction ; Telomere Shortening