Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), mimicking our body’s natural incretin hormones, have transformed metabolic disorder management. Beyond their known efficacy in blood sugar control and weight loss, emerging research reveals their profound influence on multiple cellular pathways vital to metabolic health and longevity.

This presentation explores how GLP-1 RAs enhance insulin signaling and modulate key pathways like mTOR and AMPK. They reduce oxidative stress via Nrf-2 pathway activation and impact sirtuin activity and NAD⁺ metabolism, vital for mitochondrial function and energy balance. Additionally, GLP-1 RAs exhibit anti-inflammatory effects by modulating cytokine production and immune cell polarization, affecting pathways such as JAK/STAT and NF-κB.

Importantly, GLP-1 RAs may promote positive epigenetic modifications, potentially reversing harmful changes associated with chronic metabolic diseases. Notably, by modulating aging-related pathways like p53/p21 and p16^INK4a/Rb, they may influence cellular senescence, exerting senolytic or senomodulatory effects that reduce inflammation and tissue degeneration linked to aging, disease, and cancer.

By fostering cellular efficiency and providing cytoprotection, GLP-1 RAs offer a holistic approach to restoring metabolic function and enhancing healthspan. This presentation aims to illuminate evidence supporting GLP-1 RAs as powerful peptides extending beyond weight management. Understanding their multifaceted mechanisms—including their impact on cellular senescence—highlights their potential to reshape metabolic health and improve patient outcomes through foundational metabolic and epigenetic renewal. Key takeaway points include:

– GLP-1 receptor agonists (GLP-1 RAs) have multifaceted effects beyond glucose control and weight loss, influencing multiple cellular pathways crucial for metabolic health and longevity.
– GLP-1 RAs modulate key signaling pathways such as insulin signaling, mTOR, AMPK, Nrf-2, sirtuin activity, and NAD⁺ metabolism, leading to enhanced mitochondrial function, energy balance, and reduced oxidative stress.
– GLP-1 RAs exhibit anti-inflammatory and senomodulatory properties, impacting immune cell polarization, promoting positive epigenetic modifications, and influencing cellular senescence, which may reverse harmful changes associated with chronic metabolic diseases, aging, and cancer.

Session Learning Objectives:

As a result of this activity, participants will be able to:

1.) Analyze the multifaceted mechanisms by which GLP-1 receptor agonists influence metabolic pathways beyond glycemic control and weight management.

2.) Evaluate the impact of GLP-1 RAs on cellular signaling pathways such as mTOR, AMPK, Nrf-2, and their effects on mitochondrial function, oxidative stress reduction, and energy homeostasis.

3.) Assess the potential of GLP-1 RAs in modulating inflammation and cellular senescence, including their role in epigenetic modifications and implications for treating chronic metabolic diseases, aging, and cancer.