Targeting Cellular Senescence for Age-Related Diseases: Path to Clinical Translation

Area of Science:

• Gerontology and Regenerative Medicine
• Cellular Biology
• Biomedical Sciences

Background:

• Aging is characterized by fundamental mechanisms including genomic instability, telomere attrition, and cellular senescence.
• Pathological accumulation of senescent cells contributes to age-related diseases and morbidities.
• Senescent cells are a viable target for interventions aimed at mitigating whole-body aging.

Purpose of the Study:

• To explore the potential of targeting fundamental aging mechanisms, specifically cellular senescence, for therapeutic intervention.
• To review the efficacy of senolytics and senomorphics in preclinical aging and disease models.
• To highlight the translational potential of senotherapeutics in clinical applications for age-related disorders.

Main Methods:

• Review of preclinical studies involving senolytics (senescent cell-clearing agents) and senomorphics (agents targeting senescence-associated secretory phenotype).
• Analysis of early-stage clinical trials investigating senolytic combinations (e.g., dasatinib and quercetin) and other senolytics (e.g., fisetin, BCL-xL inhibitors).
• Examination of the impact of senotherapeutics on age-related dysfunction and diseases.

Main Results:

• Preclinical studies demonstrate that senolytics and senomorphics show promise in various aging and disease models.
• Early clinical trials indicate that senolytics can alleviate age-related dysfunction, including improvements in wound healing.
• Targeting cellular senescence is a promising strategy for addressing multiple aging processes simultaneously due to their interdependence.

Conclusions:

• Senotherapeutics, including senolytics and senomorphics, represent a potential vanguard for delaying, preventing, or treating age-related disorders.
• Further multi-institutional clinical trials are necessary to validate senotherapeutics for widespread clinical application.
• Interventions targeting fundamental aging mechanisms, like cellular senescence, offer a novel approach beyond palliative care for age-related conditions.