• At 12 months: 24-hour mean growth hormone concentrations
• Insulin-like growth factor-I concentrations
• Body weight and fat mass, specifically abdominal visceral fat
• Fat-free mass
• Safety determined by routine laboratory tests at 1 to 3 month intervals, yearly pap smears and mammograms

• at 12 months: Growth hormone secretory dynamics
• Isokinetic muscle strength (knee and shoulder)
• Thigh muscle cross-sectional area
• Function tests (timed walks, stair climb, chair rise)
• Quality of life assessments
• Insulin sensitivity
• Lipid profile
• Resting metabolic rate
• Aerobic exercise capacity
• Exploratory outcomes:
• effects of gender and HRT on primary outcomes
• effects of treatment in year 2: Year 2 outcomes include effects of continuation on MK-677, or crossover to placebo, placebo to MK-677
• bone mineral density at end of year 2.

The purpose of this study is to determine whether treatment of healthy older men and women with oral MK-677 for 12 months will enhance pulsatile GH release and increase mean GH and IGF-I concentrations into the range of young adults and will have favorable effects on body composition and functional ability on older adults.

This is a two year, double-blind, placebo-controlled cross-over trial of once daily administration of MK-677, an oral GH secretagogue, to healthy older adults. During the first year, subjects will be randomized to MK-677 or placebo treatment. In each of three subgroups of subjects (men, women off and women on hormone replacement therapy), 16 subjects will receive MK-677 and 8 will receive placebo. After 1 year, the subjects who received placebo will be switched to MK-677 treatment; the subjects who received MK-677 for the first year will be randomized to either placebo or MK-677 for the second year of the study.The study will test changes in GH, IGF-I, body composition and function.

Inclusion Criteria:

• Healthy men and women  60 years of age, with a body mass index of < 35 kg/m2.

Exclusion Criteria:

• Medication known to affect GH secretion, other than estrogen replacement therapy
• Coronary artery disease,
• Congestive heart failure,
• Peripheral vascular disease,
• Diabetes mellitus (requiring insulin or an oral hypoglycemic agent),
• Significant hypertension (BP >180 systolic or >100 diastolic at rest);
• Renal, hepatic, pulmonary disease;
• Untreated hypothyroidism, untreated hyperthyroidism;
• History of seizure disorder;
• History of malignancy (other than some skin cancers), history of active chronic infections (e.g., HIV, tuberculosis).
• Hematocrit < 40%, men, < 36%, women
• History of daily tobacco use within past 3 months
• Chronic alcohol abuse
• Strenuous exercise for average of more than 60 min/day
• Investigational drug within past 6 weeks
• Psychiatric history, especially anorexia nervosa
• Transmeridian travel within 2 weeks prior to or during study