Artificially accelerated aging by shortened photoperiod alters early gene expression (Fos) in the suprachiasmatic nucleus and sulfatoxymelatonin excretion in a small primate, Microcebus murinus
F. Aujard et al., Artificially accelerated aging by shortened photoperiod alters early gene expression (Fos) in the suprachiasmatic nucleus and sulfatoxymelatonin excretion in a small primate, Microcebus murinus, NEUROSCIENC, 105(2), 2001, pp. 403-412
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.