Growth Hormone Axis and Aging
Key Points
• Growth hormone (GH) and/or ghrelin mimetics represent potential treatment and/or prevention options for musculoskeletal impairment associated with aging.
• Use of improvement in muscle function as an outcome in studies of GH and ghrelin mimetics is complicated by the lack of a standardized definition for clinically meaningful efficacy of this end point.
• Based on preliminary study results, the use of ghrelin mimetics may be more suitable for use in this age group than GH itself.
• There are still several unanswered questions related to the use of ghrelin mimetics in the elderly, which prevents recommendation for its use at the current time.
MK-677 is an orally active, long-acting Growth Hormone Secretagogue (GHS) that acts as a ghrelin mimetic at the ghrelin receptor. Ghrelin or ghrelin mimetics have been shown to enhance the preexisting pulsatile GH release and several studies demonstrate a GH increasing effect in the elderly.
In a 4-week double-blind placebo controlled study, once-daily oral MK-677, given to healthy older adults, enhances pulsatile GH release and IGF-I concentrations reaching levels seen in young adults.
A 2-year study using an orally active ghrelin mimetic in healthy older adults study found that 1-year treatment with MK-677 resulted in an increase in fat-free mass by 1.1 kg and that the effect was maintained through the second year. No significant increase in total body fat was found; however, there was a significant increase in subcutaneous limb fat.
The changes in muscle mass did not result in measurable changes in muscle strength or function. This study included mainly physically fit, active, healthy older adults. This may explain the apparent discrepancy between the increase in muscle mass and lack of detectable change in function and strength, whereas in a similar study examining frail subjects, functional improvements were detectable.
Mean Changes In Fat And Fat-Free Mass (FFM) At 12 Months Treatment With MK-677 Or Placebo In Healthy Older Adults
Limb = appendicular lean soft tissue and appendicular fat;
nonlimb = total minus limb.
Nass R. Growth Hormone Axis and Aging. Endocrinol Metab Clin North Am 2013;42(2):187-99. Growth Hormone Axis and Aging
Growth hormone (GH) and/or ghrelin mimetics represent potential treatment and/or prevention options for musculoskeletal impairment associated with aging. Use of improvement in muscle function as an outcome in studies of GH and ghrelin mimetics is complicated by the lack of a standardized definition for clinically meaningful efficacy of this end point. Based on preliminary study results, the use of ghrelin mimetics may be more suitable for use in this age group than GH itself. There are still several unanswered questions related to the use of ghrelin mimetics in the elderly, which prevents recommendation for its use at the current time.