title: Aging: functional metabolic balance among cAMP, cGMP and reactive oxygen intermediate generation by human granulocytes.
abstract: BACKGROUND
  The nature of the aging process has been the subject of considerable speculation. It has been reported that in the aging process several components of the signal transduction pathways, including phosphoinositide, protein kinase C, protein kinase A and reactive oxygen intermediate (ROI) generation, are altered.
  
  
  OBJECTIVE
  The aim of our study was to evaluate the functional metabolic balance among cAMP, cGMP and ROI generation by human neutrophils in relation to age.
  
  
  METHODS
  The age-induced ROI generation was studied in healthy subjects ranging in age from 20 to 80 years old, divided into 6 age groups: 20-29, 30-39, 40-49, 50-59, 60-69 and 70-80 years old. The oxidizing cellular generation was quantified in a luminol-dependent (ROI production) chemiluminescence assay and the results expressed as relative light units per minute.
  
  
  RESULTS
  Our results show a differential functional metabolic balance of cAMP and cGMP in relation to age from 50 years on. This phenomenon is reflected by the increase in ROI generation by neutrophil stimulation with cGMP at all ages and a simultaneous lack of effect of cAMP on cGMP from 50 years old. The same results were observed when neutrophil reacted with endogenous contents of cGMP (levamisole, an inhibitor of cGMP phosphodiesterase) or cAMP (aminophylline, an inhibitor of cAMP phosphodiesterase). Our results show that the lack of modulation of the endogenous or exogenous contents of cAMP or cGMP on ROI generation altered the age-related functional metabolic balance.
  
  
  CONCLUSIONS
  This altered functional metabolic balance in cAMP, cGMP and ROI generation of neutrophils may certainly have consequences on host defenses, mainly on inflammatory processes, in healthy subjects from 50 years old. However, the exact consequences of this phenomenon on the aging process remain unknown.
authors.affiliation: Santa Casa Hospital of Belo Horizonte, Santa Efigênia CEP, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Coelho Horta
authors.forename: Cecília
authors.initials: C
authors.lastname: Steinberg Perilo
authors.forename: Daniela
authors.initials: D
authors.lastname: Caldeira Costa
authors.forename: José Augusto
authors.initials: JA
authors.lastname: Nogueira-Machado
authors.forename: Míriam
authors.initials: M
authors.lastname: Martins Chaves
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D000242:Cyclic AMP; D006152:Cyclic GMP