Hepatocytes as Model for Investigating Natural Senotherapeutic Compounds and Their Effects on Cell Cycle Dynamics and...

Area of Science:

• Cellular Biology
• Genetics
• Pharmacology

Background:

• DNA instability leads to mutations, chromosomal abnormalities, and stalled replication/transcription.
• Accumulated DNA damage influences apoptosis and cell cycle checkpoints, initiating cellular senescence.
• Cellular senescence, characterized by blocked replication and a distinct secretory phenotype, contributes to aging and disease.

Purpose of the Study:

• To review signaling pathways governing cell cycle and senescence in mammalian cells.
• To explore the impact of senotherapeutic compounds on these pathways.
• To identify plant-derived compounds and metabolic engineering targets for senolytics and senomorphics.

Main Methods:

• Review of signaling pathways regulating cell cycle and senescence.
• Analysis of senotherapeutic compound effects on cellular dynamics.
• Identification of plant secondary metabolites with senolytic/senomorphic potential.
• Discussion of liver cells as a model for senolytic compound investigation.
• Exploration of senotherapeutics in CRISPR/Cas9 and prime-editing gene therapies.

Main Results:

• Disturbances in DNA repair, oxidative stress, and inflammation contribute to senescent cell accumulation.
• Plant secondary metabolites show promise as senolytic and senomorphic agents.
• Senotherapeutic compounds can modify cell cycle and senescence dynamics.
• Liver cells offer a viable model for studying senolytic compound effects.
• Senotherapeutics can potentially enhance gene therapy efficacy.

Conclusions:

• Senescent cell accumulation significantly impacts tissue and organismal physiology.
• Targeting cellular senescence with senotherapeutics, including plant-derived compounds, holds therapeutic potential.
• Further research into senolytic and senomorphic agents, alongside advanced gene editing, is crucial for improving health and treating age-related diseases and cancer.