Endocrine Abstracts

Healthspan is the period of life during which one enjoys good health. As people age, health is often compromised. Aging is a progressive process and changes of aging are multifactorial in origin. Growth hormone (GH) levels peak at midpuberty and thereafter decline progressively as people age. The number of GH pulses per 24 h does not change with age, but the pulse amplitude declines. The decline in GH secretion of aging is paralleled by a decline in muscle mass. This decline is muscle mass correlates with the development of frailty, although other factors also are involved. Oral ghrelin mimetics restore GH secretion in the elderly to that of 20–30 year old adults. In a placebo controlled study over one year, we demonstrated that the normal annual loss of 0.5 kg of muscle mass in subjects 60–81 years old was prevented and muscle mass increased by 1.1 kg, a difference of 1.6 kg between placebo and ghrelin-mimetic therapy (MK-677, 25 mg orally once per day). (Ann Intern Med 2008, 149: 601–611) Although there was no difference in increase in body fat between placebo and MK-677, the amount of limb fat was higher in the MK-677-treated group. GH levels and IGF-I levels increased to those of healthy young adults. Fasting blood glucose levels increased an average of 0.3 mmol/l and insulin sensitivity decreased. The most frequent side effect was an increase in appetite that subsided in most cases within 3 months. This ‘proof-of-concept’ study raises the question of whether healthspan can be extended safely by a once-a-day oral ghrelin mimetic. Our ultimate objective is to allow older individuals to enjoy good health for the maximum period of time. If we can avert the development of frailty it may extend the time that older people live independently.