Artificially accelerated aging by shortened photoperiod alters early gene expression (Fos) in the suprachiasmatic nucleus and sulfatoxymelatonin excretion in a primate. Neurosci

AbstractöIn mammals, a number of anatomical and functional changes occur in the circadian timing system with aging. In certain species, aging can be modi¢ed by various factors which induce a number of pathological changes. In a small primate, the gray mouse lemur (Microcebus murinus), long-term acceleration of seasonal rhythms by exposing the animals to a shortened photoperiodic regime (up to 2.5 times the natural photoperiodic regime) alters longevity, based on survival curves and morphological changes. This provides a model for challenging the idea that modi¢cations of the circadian pacemaker are related to chronological (years) versus biological (photoperiodic cycles) age. To assess the e¡ect of aging and accelerated aging on the circadian pacemaker of this primate, we measured body weight variations, the daily rhythm in urine 6-sulfatoxymelatonin and the light-induced expression of the immediate early gene (Fos) in the suprachiasmatic nucleus of mouse lemurs that had been exposed to di¡erent photoperiodic cycles. Urine samples were collected throughout the day and urine 6-sulfatoxymelatonin levels were measured by radioimmunoassay. Light-induced Fos expression in the suprachiasmatic nucleus was studied by exposing the animals to a 15-min mono-chromatic pulse of light (500 nm) at saturating or sub-saturating levels of irradiance (1011 or 1014 photons/cm2/s) during the dark phase. The classical pattern of 6-sulfatoxymelatonin excretion was signi¢cantly altered in aged mouse lemurs which failed to show a nocturnal peak. Fos expression following exposure to low levels of irradiance was reduced by 88% in the suprachiasmatic nucleus of aged mouse lemurs. Exposure to higher irradiance levels showed similar results, with