Aging is often associated with overweight and obesity. There exists a 
long-standing debate about whether meal pattern also contributes to the 
development of obesity. The orexigenic hormone ghrelin regulates appetite and 
satiety by activating its receptor, growth hormone secretagogue receptor 
(GHS-R). In mice, circulating ghrelin concentrations and brain GHS-R expression 
were shown to increase with aging. To assess whether GHS-R regulates feeding 
pattern during aging, we studied meal patterns for the following cohorts of male 
mice fed a normal unpurified diet: 1) 3-4 mo, young wild-type (WT) mice; 2) 3-4 
mo, young Ghsr-null (Ghsr(-/-)) mice; 3) 12-14 mo, middle-aged WT (WT-M) mice; 
4) 12-14 mo, middle-aged Ghsr(-/-) (Ghsr(-/-)-M) mice; 5) 24-26 mo, old WT 
(WT-O) mice; and 6) 24-26 mo, old Ghsr(-/-) (Ghsr(-/-)-O) mice. Although the 
total daily food intake of Ghsr(-/-) mice was similar to that of WT controls, 
Ghsr(-/-)-M and Ghsr(-/-)-O mice had 9% (P = 0.07) and 16% (P < 0.05) less body 
weight compared with WT-M and WT-O mice, respectively, primarily due to reduced 
fat mass (P < 0.05, WT-M vs. Ghsr(-/-)-M and WT-O vs. Ghsr(-/-)-O). 
Intriguingly, Ghsr(-/-)-M mice ate larger meals (on average, Ghsr(-/-)-M mice 
ate 0.117 g/meal and WT-M mice ate 0.080 g/meal; P < 0.01) and took a longer 
time to eat (Ghsr(-/-)-M, 196.0 s and WT-M, 128.9 s; P < 0.01), but ate less 
frequently (Ghsr(-/-)-M, 31.0 times/d and WT-M, 42.3 times/d; P < 0.05) than 
WT-M controls. In addition, we found that expression of hypothalamic orexigenic 
peptides, neuropeptide Y (NPY) and agouti-related peptide (AgRP), was relatively 
lower in aged WT mice (P = 0.09 for NPY and P = 0.06 for AgRP), but anorexic 
peptide pro-opiomelanocortin (POMC) expression remained unchanged between the WT 
age groups. Interestingly, old Ghsr(-/-) mice had greater hypothalamic NPY 
expression (102% higher; P < 0.05) and AgRP expression (P = 0.07) but 
significantly lower POMC expression (P < 0.05) when compared with age-matched 
WT-O controls. Thus, our results indicate that GHS-R plays an important role in 
the regulation of meal pattern and that GHS-R ablation may modulate feeding 
behavior through the regulation of hypothalamic neuropeptides. Our results 
collectively suggest that ghrelin receptor antagonism may have a beneficial 
effect on metabolism during aging.