Super Agers: An Evidence-Based Approach to Longevity

Topol explores the rise of glucagon-like peptide-1 (GLP-1) drugs and their transformative impact on two of the world’s most pressing health challenges. These medications, including Ozempic, Wegovy, Mounjaro, and Zepbound, mimic natural gut hormones that regulate metabolism and appetite. Their development was inspired by a peptide found in the saliva of the Gila monster, which led to longer-acting versions. Initially tested for diabetes, GLP-1 drugs were found to lower cardiovascular risk and later, at higher doses, produced striking weight loss results in people with obesity, often surpassing outcomes seen with gastric bypass surgery.

In response, pharmaceutical companies shifted the drugs’ branding and dosage for obesity treatment. Dual- and triple-receptor drugs such as tirzepatide and retatrutide were found to achieve weight losses of 20–24%. Topol stresses that millions might have benefited earlier had higher doses been tested sooner. Obesity, now affecting over 40% of US adults and 20% of children, has escalated dramatically since the 1990s, contributing to heart disease, cancer, diabetes, and premature death. Body mass index (BMI) remains the standard diagnostic tool; because of its flaws, Topol argues that waist circumference and fat percentage measurements are more accurate.

The chapter explores adipose (fat) biology, distinguishing between pro-inflammatory white fat, and healthier energy-burning brown fat and beige fat (convertible to brown).