Modulation of GH/IGF-1 axis: Potential strategies to counteract sarcopenia in older adults

Abstract

Aging is associated with progressive decline of skeletal muscle mass and function. This condition, termed sarcopenia, is associated with several adverse outcomes, including loss of autonomy and mortality. Due to the high prevalence of sarcopenia, a deeper understanding of its pathophysiology and possible remedies represents a high public health priority. Evidence suggests the existence of a relationship between declining growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels and age-related changes in body composition and physical function. Therefore, the age-dependent decline of GH and IGF-1 serum levels may promote frailty by contributing to the loss of muscle mass and strength. Preclinical studies showed that infusion of angiotensin II produced a marked reduction in body weight, accompanied by decreased serum and muscle levels of IGF-1. Conversely, overexpression of muscle-specific isoform of IGF-1 mitigates angiotensin II-induced muscle loss. Moreover, IGF-1 serum levels have been shown to increase following angiotensin converting enzyme inhibitors (ACEIs) treatment. Here we will review the most recent evidence regarding age-related changes of the GH/IGF-1 axis and its modulation by several interventions, including ACEIs which might represent a potential novel strategy to delay the onset and impede the progression of sarcopenia.

High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study

“…(28) Aging is associated with sarcopenia, a progressive decrease of skeletal muscle mass and function that results in various adverse outcomes (eg, loss of autonomy and death). (29) Hypersclerostinemia exists in long-term immobilized patients, and is associated with reduced bone formation, suggesting that sclerostin is a link between mechanical unloading and disuse osteoporosis in humans. (30) High circulating sclerostin may promote frailty by contributing to loss of muscle (and/or bone) mass and strength.…”

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

“…It has been proposed that low serum IGF-1 may promote frailty by contributing to the loss of muscle mass and strength. (40) In addition, treatment with combined IGF-1/IGF-binding protein 3 resulted in increased muscle strength in women with hip fracture. (35) In this context, serum IGF-1 showed a modestly positive association with both total-body lean mass and grip strength in older men in this study.…”

Sarcopenia and Functional Decline: Pathophysiology, Prevention and Therapy

“…Weak androgenic products, such as DHEA, do not appear to be interesting as a treatment option, since at best only subjective effects have been found (102,103). The use of Growth Hormone or of Insulin-Like Growth Factor 1 has been shown to have little or no benefi t in the improvement of sarcopenia (104). Also, their administration appears to be frequently accompanied by disturbing adverse effects.…”