PLASMA LEVELS OF INTERFERON-γ CORRELATE WITH AGE-RELATED DISTURBANCES OF CIRCADIAN RHYTHMS AND SURVIVAL IN A NON-HUMAN PRIMATE

Aging can be associated with changes in circadian rhythms and reduction in adaptive immune responses accompanied by expansion of memory T cells and elevated levels of pro-inflammatory cytokines. Recent findings suggest the cytokine interferon-gamma (IFN-gamma) can affect the function of the hypothalamic suprachiasmatic nucleus (SCN), the master mammalian circadian pacemaker, both in vitro and in vivo. We studied the correlation of plasma levels of IFN-gamma and changes in circadian rhythms in a non-human primate species, the nocturnal mouse lemur (Microcebus murinus). Plasma IFN-gamma and dehydroepiandrosterone sulfate (DHEA-S), a known biomarker of aging, were determined in middle- to old-age animals by immunoenzymoassay. Daily rhythms of locomotor activity and body temperature as well as survival time of the lemurs were recorded. With aging, mean levels of DHEA-S decreased whereas IFN-gamma increased. Aged animals showed biological rhythm alterations characterized by a high percentage of diurnal activity, anticipation of the activity onset relative to lights-off, short free-running period, and delayed occurrence of minimal body temperature. The magnitude of these disturbances was correlated with the plasma level of IFN-gamma but not DHEA-S. Most remarkably, in contrast to DHEA-S, increased levels of IFN-gamma correlated with duration of the lifetime of the lemurs. These results show the degree of circadian rhythm alterations in an individual is correlated with plasma IFN-gamma level during aging, and that plasma IFN-gamma level may predict survival, at least in this non-human primate. (Author correspondence: fabienne.aujard@wanadoo.fr)