Targeting normal and cancer senescent cells as a strategy of senotherapy

Area of Science:

• Gerontology and Cellular Aging
• Immunology
• Pharmacology

Background:

• Cellular senescence, characterized by the accumulation of senescent cells with age, is linked to age-related diseases.
• Senescent cells exhibit a detrimental secretory phenotype (SASP), contributing to tissue dysfunction.
• Senotherapy aims to counteract aging by targeting senescent cells.

Purpose of the Study:

• To review the current state of senotherapy as an anti-aging strategy.
• To discuss the potential benefits and challenges of translating senotherapy to human applications.
• To explore the implications of senotherapy in cancer treatment.

Main Methods:

• Review of genetic approaches demonstrating senescent cell elimination in preclinical models.
• Discussion of senolytic agents (synthetic and natural compounds) for targeting senescent cells.
• Analysis of strategies to modulate the immune system's role in senescent cell clearance and SASP.

Main Results:

• Genetic elimination of senescent cells in mice provides proof-of-concept for therapeutic potential in age-related diseases.
• Senolytic agents offer a promising avenue for human translation of senotherapy.
• Challenges include ensuring efficacy, safety, and tolerability in humans, and understanding effects on non-dividing cells.

Conclusions:

• Senotherapy holds significant promise for improving healthspan by targeting senescent cells.
• Further research is crucial to overcome challenges in human application and address potential risks, such as cancer cell renewal.
• Developing effective senotherapeutic strategies is vital for both anti-aging and cancer treatment.