Somatotrope GHRH/GH/IGF‐1 axis at the crossroads between immunosenescence and frailty

Abstract

Immunosenescence, characterized by complex modifications of immunity with age, could be related to frailty syndrome in elderly individuals, leading to an inadequate response to minimal aggression. Functional decline (i.e., the loss of ability to perform activities of daily living) is related to frailty and decreased physiological reserves and is a frequent outcome of hospitalization in older patients. Links between immunosenescence and frailty have been explored and 20 immunological parameters, including insulin-like growth factor-1 (IGF-1), thymopoeisis, and telomere length, were shown to be affected in elderly patients with functional decline. A strong relationship between IGF-1 and thymic ouput was evidenced. IGF-1, a mediator of growth hormone (GH), was subsequently shown to induce interleukin-7 secretion in cultured primary human thymic epithelial cells. We are exploring the stress hypothesis in which an acute stressor is used as the discriminator of frailty susceptibility. GH can counteract the deleterious immunosuppressive effects of stress-induced steroids. Under nonstress conditions, the immunosenescent system preserves physiological responses, while under stress conditions, the combination of immunosenescence and a defect in the somatotrope axis might lead to functional decline.

Increased longevity due to sexual activity in mole-rats is associated with transcriptional changes in the HPA stress axis

“…This gene was found to be expressed most strongly in ovary and liver and was strongly up-regulated in the breeders´ ovaries and adrenal glands (Table 1). IGF1 codes for a well-known key regulator of anabolic effects such as cell proliferation, myogenesis, and protein synthesis (Schiaffino and Mammucari 2011;Jung and Suh 2014) and has a tight functional relation to GH (gene: GH1) another key anabolic regulator upstream of IGF1; together, these factors form the so-called GH/IGF1 axis (Cannata et al 2010;Junnila et al 2013;Bodart et al 2015;Raisingani et al 2017;Carotti et al 2018;Lozier et al 2018). Also, GH1 was strongly up-regulated in breeders in its known principal place of synthesis, the pituitary gland (Table 1).…”

Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

“…These findings suggest that IGF-1 occupies an important role in GH-mediated enhancement of T cell production and offer fundamental insight into the mechanism of GH effects on the human immune system [32]. More recently, IGF-1, a proximal mediator of the metabolic action of GH, was found to induce expression and release of IL-7 in cultured human thymic epithelial cells [33]. …”

The basic route of nuclear‐targeted transport of IGF‐1/IGF‐1R and potential biological functions in intestinal epithelial cells

“…IGF-1 is also referred to as the growth-promoting factor. 4 This peptide-protein is similar to insulin in molecular structure. Recent research evidence shows that IGF-1 has significant biological effects in the intestines.…”

“…Among them, IGF‐1 constitutes an important cytokine associated with the differentiation, proliferation and maturation of body tissues. IGF‐1 is also referred to as the growth‐promoting factor 4 . This peptide‐protein is similar to insulin in molecular structure.…”