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Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin

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Abstract

In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master clock and by generation of temporal oscillations regulates the peripheral organs acting as autonomous clocks resulting in overt behavioral and physiological rhythms. SCN also controls synthesis and release of melatonin (hormonal message for darkness) from pineal. Nitric Oxide (NO) acts as an important neurotransmitter in generating the phase shifts of circadian rhythms and participates in sleep–wake processes, maintenance of vascular tone as well as signalling and regulating inflammatory processes. Aging is associated with disruption of circadian timing system and decline in endogenous melatonin leading to several physiological disorders. Here we report the effect of aging on NO daily rhythms in various peripheral clocks such as kidney, intestine, liver, heart, lungs and testis. NO levels were measured at zeitgeber time (ZT) 0, 6, 12 and 18 in these tissues using Griess assay in male Wistar rats. Aging resulted in alteration of NO levels as well as phase of NO in both 12 and 24 months groups. Correlation analysis demonstrated loss of stoichiometric interaction between the various peripheral clocks with aging. Age induced alterations in NO daily rhythms were found to be most significant in liver and, interestingly least in lungs. Neurohormone melatonin, an endogenous synchroniser and an antiaging agent decreases with aging. We report further differential restoration with exogenous melatonin administration of age induced alterations in NO daily rhythms and mean levels in kidney, intestine and liver and the stoichiometric interactions between the various peripheral clocks.

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Acknowledgments

The work is supported by ICMR (Ref. No. BMS/NTF/14/2006-2007; 55/7/2012-/BMS), UGC (Ref: F. No.: 32-613/2006 (SR) and UPE grants to AJ. Ch Vinod is thankful to UGC for fellowship.

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  1. Neurobiology and Molecular Chronobiology Lab, Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, 500046, India

    Ch. Vinod & Anita Jagota

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Correspondence to Anita Jagota.

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Vinod, C., Jagota, A. Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin. Biogerontology 17, 859–871 (2016). https://doi.org/10.1007/s10522-016-9656-6

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