XXXX buffering systems and @entity460 signaling in aged @entity35 basal forebrain neurons.

@entity35 @entity303 @entity73 @entity460 @entity141
Disturbances of neuronal @entity141 homeostasis are considered to be important determinants of age-related @entity73 . Cholinergic neurons of the basal forebrain (BF) are principal targets of decline associated with aging and @entity303 . During the last several years, we have attempted to link these concepts in a @entity35 model of 'normal' aging. In this review, we will describe some changes that we have observed in @entity141 signaling of aged BF neurons and the reversal of one of these changes by dietary caloric restriction. Our evidence supports a scenario in which subtle changes in the properties of voltage-gated @entity141 channels result in increased @entity141 influx during aging. This increased @entity141 , in turn, triggers an increase in rapid @entity141 buffering in the somatic compartment of aged BF neurons. However, this nominal 'compensation', along with other changes in @entity141 handling machinery (notably mitochondria) alters the @entity141 signal with age in a way that is dependent on the magnitude of the @entity141 load. By combining whole-cell patch clamp electrophysiology, ratiometric @entity141 -sensitive microfluorimetry and single-cell reverse transcription-polymerase chain reaction, we have determined that age-related rapid buffering changes are present in identified cholinergic BF neurons and that these changes can be prevented by a caloric restriction dietary regimen. Because caloric restriction extends lifespan and retards the progression of age-related dysfunction, these findings suggest that increased @entity141 buffering in cholinergic neurons may be relevant to @entity73 during normal aging. Importantly, @entity460 homeostatic mechanisms of BF cholinergic neurons are amenable to dietary interventions that could promote cognitive health during aging.
