RISING STARS: Targeting premature cellular senescence using senomorphic or senolytic agents to impact diabetes

Area of Science:

• Gerontology
• Metabolic Diseases
• Cell Biology

Background:

• Type 2 diabetes mellitus (DM) is strongly linked to cellular senescence (SnC), characterized by irreversible cell cycle arrest and functional decline.
• Oxidative stress, DNA damage, and telomere shortening mechanistically link SnC to type 2 DM pathogenesis and progression.
• Senescent cells accumulate in metabolically active tissues, exacerbating the chronic inflammatory environment in diabetes.

Purpose of the Study:

• To elucidate the role of cellular senescence in the pathogenesis and progression of type 2 DM.
• To explore the potential of senotherapeutics as adjunct therapies for type 2 DM.
• To highlight the need for clinical trials to evaluate senotherapeutic efficacy and safety.

Main Methods:

• Review of in vitro and preclinical studies.
• Analysis of the senescence-associated secretory phenotype (SASP) in diabetes.
• Exploration of senomorphic and senolytic agents.

Main Results:

• Cellular senescence contributes to impaired β-cell function, insulin resistance, and systemic complications in type 2 DM.
• The senescence-associated secretory phenotype drives tissue damage via paracrine and autocrine signaling.
• Senotherapeutics show promise in preclinical models for mitigating DM progression and complications.

Conclusions:

• Targeting cellular senescence presents a promising therapeutic strategy for type 2 diabetes.
• Senomorphic and senolytic agents offer potential benefits in managing DM and its comorbidities.
• Clinical translation of senotherapeutics is crucial to validate their safety and efficacy in patients.