Inflammation as an Important Mechanism in the Role of Growth Hormone in Aging
Interfering in growth hormone signaling has been shown to extend life considerably in mice. Unfortunately, the analogous human populations with Laron syndrome resulting from loss of function mutations in the growth hormone receptor gene do not live notably longer than the rest of us. Thus the most important mechanisms linking growth hormone metabolism to longevity must produce smaller effects as species life span increases. Here, researchers suggest that growth hormone shortens life because it produces greater chronic inflammation in old age. Inflammation is known to drive age-related disease and mortality, which adds to the puzzle of why it is that the effects of growth hormone metabolism on life span are so small in humans versus mice.
While inflammation is a crucial response in injury repair and tissue regeneration, chronic inflammation is a prevalent feature in various chronic, non-communicable diseases such as obesity, diabetes, and cancer and in cardiovascular and neurodegenerative diseases. Long-term inflammation considerably affects disease prevalence, quality of life, and longevity. Our research indicates that the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is a pivotal regulator of inflammation in some tissues, including the hypothalamus, which is a key player in systemic metabolism regulation.
Moreover, the GH/IGF-1 axis is strongly linked to longevity, as GH- or GH receptor-deficient mice live approximately twice as long as wild-type animals and exhibit protection against aging-induced inflammation. Conversely, GH excess leads to increased neuroinflammation and reduced longevity. Our review studies the associations between the GH/IGF-1 axis, inflammation, and aging, with a particular focus on evidence suggesting that GH receptor signaling directly induces hypothalamic inflammation. This finding underscores the significant impact of changes in the GH axis on metabolism and on the predisposition to chronic, non-communicable diseases.