Since certain functions mediated by nitric oxide (NO) decline with age
, the age dependence of NO production by macrophages from BALB/c mice
was investigated. Lipopolysaccharide-, peptido-glycan-polysaccharide-,
or interferon-gamma-stimulated splenic and peritoneal macrophages fro
m young (1 month old), middle-aged (4-5 months old), and old (6-20 mon
ths old) BALB/c mice showed a progressive and marked decline in NO pro
duction. This age-related decline in inducible NO extended to C57/BL6
and CB6F1 mice. mRNA for inducible NO synthase (iNOS), the enzyme resp
onsible for inducible NO production by macrophages, also declined with
age. Importantly, the reduced NO production by macrophages from old m
ice could be up-regulated by pretreating the mice with either cholera
toxin or concanavalin A. These findings indicate that reduced producti
on of NO by murine macrophages correlates directly with advancing age,
likely due to deficient signals or signal transduction responsible fo
r iNOS mRNA and protein generation.