Cellular senescence and senolytics: the path to the clinic

Area of Science:

• Gerontology and molecular biology
• Cellular biology and disease mechanisms

Background:

• Aging involves fundamental processes, including cellular senescence, a state of cell cycle arrest.
• Persistent senescent cells secrete harmful proteins, impairing tissue function and contributing to various disorders.
• Cellular senescence is implicated as a root cause in numerous age-related diseases and conditions.

Purpose of the Study:

• To review the rationale for targeting senescent cells therapeutically.
• To discuss senolytic drugs and other interventions for clearing senescent cells.
• To explore the translation of these strategies into clinical practice for human diseases.

Main Methods:

• Review of preclinical models demonstrating the efficacy of senescent cell targeting.
• Analysis of the mechanisms by which senescent cells impact tissue function.
• Examination of current clinical trials involving senolytics and other senescence-targeting therapies.

Main Results:

• Preclinical studies show interventions targeting senescent cells can prevent or alleviate multiple disorders.
• Small-molecule senolytic drugs selectively clear senescent cells, offering therapeutic potential.
• Numerous clinical trials are investigating senolytics for human diseases and age-related conditions.

Conclusions:

• Cellular senescence is a viable therapeutic target for a range of disorders throughout life.
• Senolytic drugs and other senescence-targeting interventions represent promising strategies for human health.
• Translating these findings into clinical use is advancing through ongoing research and trials.