Targeting cellular senescence with senotherapeutics: senolytics and senomorphics

Area of Science:

• Geroscience
• Cellular senescence
• Therapeutic targets

Background:

• Aging is the primary risk factor for numerous diseases.
• Cellular senescence, a state of irreversible cell cycle arrest, is a key hallmark of aging.
• Senescent cells (SnCs) exhibit a pro-inflammatory Senescence-Associated Secretory Phenotype (SASP) contributing to tissue dysfunction.

Purpose of the Study:

• To review the development of senotherapeutics (senolytics and senomorphics).
• To discuss their potential for treating age-related diseases and extending healthspan.
• To examine challenges in preclinical documentation and current clinical applications.

Main Methods:

• Review of current literature on senolytics and senomorphics.
• Analysis of senescent cell biology and therapeutic targeting.
• Discussion of preclinical and clinical evidence.

Main Results:

• Senolytics selectively eliminate SnCs, while senomorphics suppress the SASP.
• Both approaches target key pathways altered in SnCs, including anti-apoptotic pathways.
• Senotherapeutics show promise in preclinical models for age-related conditions.

Conclusions:

• Senolytics and senomorphics represent a promising therapeutic strategy within geroscience.
• Further research is needed to overcome challenges in preclinical validation and clinical translation.
• Senotherapeutics hold potential for treating age-related diseases and promoting healthy longevity.