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 circ adian timing system with aging. In certain species, aging can be modified b y 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 r egime (up to 2.5 times the natural photoperiodic regime) alters longevity, based on survival curves and morphological changes. This provides a model f or challenging the idea that modifications of the circadian pacemaker are r elated to chronological (years) versus biological (photoperiodic cycles) ag e. To assess the effect of aging and accelerated aging on the circadian pacema ker of this primate, we measured body weight variations, the daily rhythm i n urine 6-sulfatoxymelatonin and the light-induced expression of the immedi ate early gene (Fos) in the suprachiasmatic nucleus of mouse iemurs that ha d been exposed to different photoperiodic cycles. Urine samples were collec ted throughout the day and urine 6-sulfatoxymelatonin levels were measured by radioimmunoassay. Light-induced Fos expression in the suprachiasmatic nu cleus was studied by exposing the animals to a 15-min monochromatic pulse o f light (500 nm) at saturating or sub-saturating levels of irradiance (10(1 1) or 10(14) photons/cm(2)/s) during the dark phase. The classical pattern of 6-sulfatoxymelatonin excretion was significantly altered in aged mouse l emurs which failed to show a nocturnal peak. Fos expression following expos ure to low levels of irradiance was reduced by 88% in the suprachiasmatic n ucleus of aged mouse lemurs, Exposure to higher irradiance levels showed si milar results, with a reduction of 66% in Fos expression in the aged animal s, Animals subjected to artificially accelerated aging demonstrated the sam e 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 a nd in the cellular response to photic input in the suprachiasmatic nucleus of aged mouse lemurs, and that these alterations depend on the number of ex pressed seasonal cycles rather than on a fixed chronological age. These res ults provide new insights into the mechanisms underlying artificial acceler ated aging at the level of the molecular mechanisms of the biological clock . (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.