Is ghrelin a potential signal of decreased fat-free mass in elderly subjects?

Aging is associated with weight loss, appetite decline, reduced fat-free mass (FFM) and increased fat mass (FM). Dysregulation of the ghrelin and leptin systems could reduce hunger and promote early satiety in elderly subjects, leading to impairment of the nutritional status. To better clarify this issue, we evaluated the response of plasma ghrelin and leptin to a standardised oral mixed nutrient load (SOMNL) in elderly subjects with different body composition. The study population, including 36 elderly subjects (14/12 F/M, 68.6±4 yrs; 16 overweight/obese and 10 normal-weight) and 10 young healthy controls, was subjected to air plethismography (BOD POD) for FM and FFM and DEXA for appendicular skeletal muscle mass (ASMM) to assess body composition. Plasma ghrelin, leptin, growth hormone (GH), glucose and insulin concentrations were measured before and 1 h after SOMNL (19% protein, 35% lipids, 46% carbohydrates; 478 Kcal). In obese elderly subjects, basal ghrelin was lower and leptin was higher than in normal-weight elderly subjects, as expected. Leptin was higher in elderly subjects than in young controls, whereas ghrelin was similar in both age groups. After SOMNL, ghrelin was more suppressed in normal-weight than in obese elderly subjects (−23% vs −12.4%, P<0.05) and in controls, whereas leptin and GH variations were similar. Basal and post-SOMNL ghrelin concentrations were inversely related to FFM, ASMM and to insulin sensitivity (QUICKI), whereas basal and post-SOMNL leptin levels were directly related to FM. The present data suggest that, in elderly subjects, ghrelin concentrations, both basal and after SOMNL, are sensitive to the depletion of FFM (and specifically to the amount of skeletal muscle), similar to the sensitivity of leptin concentrations to relative increments of FM. The greater ghrelin suppression in normal-weight elderly subjects could represent a signal of early satiety, leading to a reduction of food intake.