Amelioration of Age-Related Deficits in the Stimulation of Synapsin Phosphorylation

In a previous report we demonstrated that aged (24–26 month) rats have deficits in long-term potentiation, a form of synaptic enhancement that is dependent on protein phosphorylation (Moore et al., Hippocampus, 3:57–66; 1993). In the present study we demonstrate that aged rats have a deficit in the phosphorylation of the synaptic vesicle associated protein synapsin I. Specifically, aged animals exhibit defective phorbol ester-induced stimulation of synapsin phosphorylation at its calcium/calmodulin dependent protein kinase II sites. We also examined the effects of caloric restriction and antioxidant therapy on this age-related deficit. We found that either life-long caloric restriction or treatment with 16 mg/kg N-tert-butyl-α-phenylnitrone (PBN) for 2 weeks can at least partially ameliorate the age-related deficit in the phorbol ester stimulation of synapsin phosphorylation.