Senotherapy: A New Horizon for COPD Therapy.

Area of Science:

• Gerontology
• Pulmonology
• Pharmacology

Background:

• COPD is increasingly recognized as a disease of accelerated lung aging.
• Cellular senescence, characterized by the senescence-associated secretory phenotype (SASP), contributes to COPD pathogenesis.
• SASP mimics inflammatory mediators found in COPD, highlighting a shared aging pathway.

Purpose of the Study:

• To review novel senotherapies targeting cellular senescence as a potential therapeutic strategy for COPD.
• To explore the role of phosphoinositide-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling and mitochondrial oxidative stress in COPD-related aging.
• To discuss the potential of senolytics and senostatics in managing COPD and its comorbidities.

Main Methods:

• Review of existing literature on cellular senescence, COPD, and senotherapeutic agents.
• Discussion of molecular pathways implicated in COPD aging, including PI3K/mTOR signaling and sirtuin regulation.
• Exploration of senolytic and senostatic drug mechanisms and their preclinical/clinical evidence.

Main Results:

• Cellular senescence and SASP are key features of COPD, mirroring accelerated aging.
• PI3K/mTOR signaling and mitochondrial oxidative stress drive senescence in COPD.
• Loss of antiaging molecules like sirtuin-1 and sirtuin-6 is linked to COPD via microRNA-34a.
• Senolytic therapies demonstrate efficacy in removing senescent cells and reducing SASP in aging models.
• Combination therapies (senolytics and senostatics) show promise for early COPD intervention.

Conclusions:

• Senotherapies targeting cellular senescence represent a promising therapeutic avenue for COPD.
• Addressing shared aging pathways may offer a unified treatment approach for COPD and its comorbidities.
• Early intervention with senolytics and senostatics could potentially mitigate COPD progression and improve health span.