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

In mammals, a number of anatomical and functional changes occur in the circadian timing system with aging. In certain species, aging can be modified 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 modifications of the circadian pacemaker are related to chronological (years) versus biological (photoperiodic cycles) age. To assess the effect 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 different 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 monochromatic pulse of light (500 nm) at saturating or sub-saturating levels of irradiance (10(11) or 10(14) photons/cm(2)/s) during the dark phase. The classical pattern of 6-sulfatoxymelatonin excretion was significantly 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 a reduction of 66% in Fos expression in the aged animals. Animals subjected to artificially accelerated aging demonstrated the same alterations in melatonin production and Fos response to light as animals that had been maintained in a routine photoperiodic cycle. Our data indicate that there are dramatic changes in melatonin production and in the cellular response to photic input in the suprachiasmatic nucleus of aged mouse lemurs, and that these alterations depend on the number of expressed seasonal cycles rather than on a fixed chronological age. These results provide new insights into the mechanisms underlying artificial accelerated aging at the level of the molecular mechanisms of the biological clock.