Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults

Abstract

Background: Acyl-ghrelin is thought to have both orexigenic effects and to stimulate GH release. A possible cause of the anorexia of aging is an age-dependent decrease in circulating acyl-ghrelin levels.

Objectives: The purpose of the study was to compare acyl-ghrelin and GH concentrations between healthy old and young adults and to examine the relationship of acyl-ghrelin and GH secretion in both age groups.

Methods: Six healthy older adults (age 62-74 y, body mass index range 20.9-29 kg/m(2)) and eight healthy young men (aged 18-28 y, body mass index range 20.6-26.2 kg/m(2)) had frequent blood samples drawn for hormone measurements every 10 minutes for 24 hours. Ghrelin was measured in an in-house, two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in a sensitive assay (Immulite 2000), and GH peaks were determined by deconvolution analysis. The acyl-ghrelin/GH association was estimated from correlations between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-minute interval preceding each GH burst.

Results: Twenty-four-hour mean (±SEM) GH (0.48 ± 0.14 vs 2.2 ± 0.3 μg/L, P < .005) and acyl-ghrelin (14.7 ± 2.3 vs 27.8 ± 3.9 pg/mL, P < .05) levels were significantly lower in older adults compared with young adults. Twenty-four-hour cortisol concentrations were higher in the old than the young adults (15.1 ± 1.0 vs 10.6 ± 0.9 μg/dL, respectively, P < .01). The ghrelin/GH association was more than 3-fold lower in the older group compared with the young adults (0.16 ± 0.12 vs 0.69 ± 0.04, P < .001).

Conclusions: These results provide further evidence of an age-dependent decline in circulating acyl-ghrelin levels, which might play a role both in the decline of GH and in the anorexia of aging. Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are less tightly linked to GH regulation.

Figure 1.

Twenty-four-hour mean (±SEM) profiles of acyl-ghrelin (left axis) and GH (right axis, note log scale) in six healthy older adults (A) and eight healthy young men (B); young adults are included for comparison from Nass et al (13). Note different scales for old (upper panel) and young (lower panel) between groups. Arrows indicate standardized meals at 8:00 am, 1:00 pm, and 6:00 pm. Subjects were allowed to sleep after 9:00 pm. Also, note that in the older adults, GH was assayed in singlicates, which may contribute to some additional measurement variability in this group.

Figure 2.

Twenty-four-hour mean (±SEM) cortisol profiles in six healthy older adults and eight healthy young adults. Arrows indicate standardized meals at 8:00 am, 13:00 pm, and 18:00 pm. Subjects were allowed to sleep after 9:00 pm.

Figure 3.

Comparison of 12-hour mean (±SEM) concentrations of acyl-ghrelin (panels A and B), GH (panels C and D), insulin (panels E and F), and cortisol (panels G and H) during the day (8:00 am to 800 pm) (left column) and night (8:00 to 8:00 am) (right column) in six old and eight young adults on a fed admission; standardized meals at 8:00 am, 1:00 pm, and 6:00 pm. *, P < .005 old vs young.

Figure 4.

Mean (±SEM) maximal LA assessing the strength of the relationship between acyl-ghrelin concentration and GH secretion in old (n = 6) vs young (n = 8) adults. *, P < .001.

Figure 5.

Mean (±SEM) LA at different lags (δ = 0, …, 120 min). The rectangle outlines the LA values in the 1-hour lag interval before the GH pulse. The asterisk over the rectangle indicates that the LA in the 1-hour interval before the GH pulse is significantly higher in the young adults. The two asterisks indicate that the LA at the time points t = 0, 30, and 60 minutes is significantly higher in the young adult group.