Growth Hormone Secretagogues: How They Work and Their Role in Aging

Aging is characterized by a natural decline in growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, a phenomenon known as somatopause. This decline contributes to various age-related issues such as decreased muscle mass (sarcopenia), increased body fat, and reduced bone density. Understanding the mechanisms of growth hormone secretagogues (GHS) and their potential to counteract these age-related physiological changes is crucial for improving healthspan and quality of life in older adults.

The review elucidated that GHS primarily act by binding to the ghrelin receptor (GHS-R1a), leading to a robust, pulsatile release of GH from the anterior pituitary gland. Studies consistently demonstrated that GHS could significantly elevate GH and IGF-1 levels in older adults, often restoring them to concentrations observed in younger individuals, with some trials reporting GH increases of 2-3 fold and IGF-1 increases ranging from 30% to 60% over baseline. The most compelling finding was that GHS effectively reversed several aspects of somatopause, showing a significant increase in lean body mass (e.g., 2-5 kg over 6-12 months) and a concomitant decrease in fat mass (e.g., 1-3 kg) in numerous clinical investigations. This improvement in body composition was often achieved without the severe adverse effects associated with exogenous GH administration. However, the impact on bone mineral density and muscle strength was less consistent across studies, with some reporting modest improvements (e.g., a 1-2% increase in lumbar spine bone density) while others found no statistically significant changes.