Abstract
Suprachiasmatic nucleus (SCN) in synchronization with the peripheral clocks regulates the temporal oscillations leading to overt rhythms. Aging leads to attenuation of such circadian regulation, accompanied by increased inflammatory mediators prevalently the cytokines. Suppressors of cytokine signaling (SOCS) family of proteins such as SOCS 1, 3 and cytokine-inducible SH2-containing protein (CIS) negatively regulate the cytokine signaling pathway. The role of SOCS1 in aging and circadian system is obscure. We therefore studied the daily rhythms of rSocs1 mRNA expression at Zeitgeber time (ZT) -0, 6, 12 and 18 in peripheral clocks such as liver, kidney, intestine and heart of 3, 12 and 24months (m) old male Wistar rats. Interestingly the peripheral clocks studied displayed a rhythmic rSocs1 gene expression in 3months. In 12months group, 12h phase advance in liver and 12h phase delay in kidney and heart was observed with abolition of rhythms in intestine. Aging (24months group) resulted in a phase advance by 6h in liver and heart with abolition of rhythms in intestine in 24months group. Kidney was also significantly affected upon aging with significant decrease in the rSocs1 levels and abolition of rhythms. The decrease in melatonin levels with aging is associated with decreased immunity and increased oxidative stress. The exogenous administration of melatonin has been linked to play a role in re-synchronization of circadian rhythms, reducing oxidative stress and enhancing immune properties. We therefore had studied the effect of exogenous melatonin upon age induced changes in daily rSocs1 gene expression patterns. Melatonin treatment partially restored the rhythms and daily pulse (ratio of maximum:minimum levels) in liver and intestine in 12months group. Melatonin administration resulted in a significant increase in mean 24h rSocs1 expression in intestine and heart of 24months group compared to that of 3months. The melatonin administration resulted in differential restoration of rSocs1 rhythms and levels in various tissues of 24months old group. The sensitivity of 24months old animals to melatonin found in the present study is a step towards endorsing melatonin as an important anti-aging therapeutic drug.
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