Growth hormone and aging: a clinical review

Abstract

Aging is a complex biological process characterized by functional decline, reduced quality of life, and increased vulnerability to diseases such as type 2 diabetes, cardiovascular conditions, neurodegeneration, and cancer. Advances in medical technology have introduced the concept of aging therapies, with growth hormone (GH) and its primary mediator, insulin-like growth factor 1 (IGF-1), receiving considerable attention for their potential to counteract age-related physiological and metabolic changes. GH plays a multifaceted role in the human body, primarily influencing body composition by increasing muscle mass, reducing fat tissue, promoting bone formation, and regulating the metabolism of proteins, lipids, and glucose. Additional effects have been noted on endothelial function, cognitive performance, and circadian rhythms. This review examines the molecular mechanisms of GH in aging, its potential as an anti-aging therapy, and findings from clinical trials involving these hormones for this purpose. It also addresses the associated adverse effects, limitations, and controversies. While some studies report significant benefits, these therapies' long-term safety and efficacy in promoting healthy aging remain uncertain, highlighting the need for further research.

Keywords: aging; anti-aging treatments; human growth hormone; human growth hormone deficiency; insulin-like growth factor I.

FIGURE 1

Upstream and downstream regulation of HGH. The release of HGH is regulated by multiple signals in the hypothalamus. GHRH secreted by neurons in the arcuate nucleus, stimulates HGH production in the anterior pituitary gland. In contrast, somatostatin, secreted by the periventricular nucleus of the hypothalamus, inhibits HGH release. Factors such as catecholamines, serotonin, and dopamine modulate GHRH secretion, while ghrelin, primarily secreted by the stomach during fasting conditions, enhances HGH release. HGH directly affects various tissues, stimulating protein synthesis in muscles, lipolysis in adipose tissue, and chondrocyte differentiation in bones. It also acts indirectly through IGF-1, which is primarily produced in the liver and mediates bone growth and anabolic metabolism. IGF-1 also has a direct effect in the modulation of GHRH secretion inhibiting the arcuate nucleus cells and the production of HGH in the pituitary gland; IGF-1 stimulates the production of somatostatin.

FIGURE 2

HGH and its multiple functions in the body. Beyond promoting growth during childhood and adolescence, HGH maintains homeostasis, supports body composition, and sustains overall metabolic balance and well-being. HGH is critical in improving bone remodeling, preventing sarcopenia, and enhancing vascular elasticity. Additionally, it influences insulin resistance, impacting metabolic balance, and helps prevent immunosenescence, thus supporting overall health during aging. While it continues to influence numerous organs and systems throughout adulthood, its effects gradually diminish as individuals advance into older age.