Targeting senescent cells: approaches, opportunities, challenges.

Area of Science:

• Gerontology and Cellular Biology
• Molecular Biology and Immunology

Background:

• Cellular senescence is a fundamental aging process with dual roles, impacting development, tumor suppression, and organismal health.
• Senescent cells can exert beneficial effects acutely but become detrimental chronically, promoting inflammation and cancer via the senescence-associated secretory phenotype (SASP).

Purpose of the Study:

• To review current therapeutic strategies targeting cellular senescence for aging-related diseases and cancer.
• To discuss the advantages and disadvantages of senolytic, SASP inhibition, and immune-enhancement therapies.

Main Methods:

• Literature review of cellular senescence mechanisms and therapeutic interventions.
• Analysis of the impact of senescent cell persistence on organismal health.
• Discussion of senolytic, SASP inhibition, and immunosurveillance strategies.

Main Results:

• Short-term senescent cells aid tissue repair, while long-term cells promote chronic disease through SASP.
• Therapeutic approaches include senolytics, SASP inhibitors, and enhancing immunosurveillance.
• Cancer therapies may induce senescence but require clearance of senescent-like cells to prevent pro-tumorigenic states.

Conclusions:

• Targeting cellular senescence offers promising avenues for treating age-related diseases.
• Balancing the transient benefits of senescence with the risks of chronic SASP is crucial for therapeutic success.
• Further research is needed to optimize therapies that selectively eliminate harmful senescent cells or mitigate their effects.