Dysregulation of neuropeptides may play an important role in aging-induced impairments.
In the long list of neuropeptides, pituitary adenylate cyclase-activating polypeptide
(PACAP) represents a highly effective cytoprotective peptide that provides an endogenous
control against a variety of tissue-damaging stimuli. PACAP has neuro- and general
cytoprotective effects due to anti-apoptotic, anti-inflammatory, and antioxidant actions.
As PACAP is also a part of the endogenous protective machinery, it can be hypothesized
that the decreased protective effects in lack of endogenous PACAP would accelerate
age-related degeneration and PACAP knockout mice would display age-related degenerative
signs earlier. Recent results support this hypothesis showing that PACAP deficiency
mimics aspects of age-related pathophysiological changes including increased neuronal
vulnerability and systemic degeneration accompanied by increased apoptosis, oxidative
stress, and inflammation. Decrease in PACAP expression has been shown in different
species from invertebrates to humans. PACAP-deficient mice display numerous pathological
alterations mimicking early aging, such as retinal changes, corneal keratinization
and blurring, and systemic amyloidosis. In the present review, we summarize these
findings and propose that PACAP deficiency could be a good model of premature aging.