Growth hormone, inflammation and aging

Abstract

Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1) constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor/growth hormone binding protein knockout (GHRKO) mice characterized by GH resistance live significantly longer than genetically normal animals. During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines. This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

Obesity and related consequences to ageing

“…The rate of ageing varies across species and is genetically based (Bowen and Atwood 2004). In humans, the ageing phenotype is characterized by hearing loss, visual impairment (Roth 2015), wrinkles and other skin conditions (Yosipovitch et al 2007), a steady decline in many cognitive processes (Deary et al 2009), a decrease in sex and growth hormones (Masternak and Bartke 2012), and increased inflammation (Starr et al 2009). The elderly are the fastest-growing segment of the population, and it is estimated that by 2050, there will be two billion people over the age 60 and they will outnumber the children (Glatt et al 2007).…”

“…Reduced growth hormone (GH, called also somatotropin) level emerges as biomarker of ageing as well as a suspected causal factor in various symptoms and functional deficits associated with the ageing process (Masternak and Bartke 2012). The hormones, which have increasing levels at puberty, such as GH, strongly affect body composition and strength.…”

Age-related changes of malondialdehyde, body weight and organ weight in male mice

“…(7) One study showed weight increase and hypertrophy of white adipose tissue (WAT) with age in the internal organs and subcutaneous tissues. (29) Secretion of the pro-inflammatory cytokines TNF-α and IL-6 by adipocytes and accumulation of macrophages in adipose tissue causes a chronic systemic inflammatory condition (inflammaging), (30) resulting in DNA damage and degeneration in various body tissues. Other studies showed that aging increases foci of DNA damage in various organs, such as the lungs, liver, and spleen.…”

In case of obesity, longevity-related mechanisms lead to anti-inflammation

“…Plasma IL-6 level and insulin sensitivity relationship is very remarkable and there is a very strong controversial connection between them (Kern et al 2001). It is suggested that the shift of the secretory profile of adipose tissue from pro-to anti-inflammatory importantly contributes to improved insulin sensitivity-reduced rate of aging and extended longevity in mice lacking GH signals (Masternak and Bartke 2012). It is said that the exercise program applied along with low-calorie diet could decrease the inflammation rate by reducing the plasma levels of some cytokines like IL-6, CRP, and TNF-α (Brunn et al 2006).…”