Melatonin’s role in ameliorating perturbed circadian immune molecular links with aging and sleep deprivation in central and peripheral clocks in male Wistar rats

📖 Top 20% JournalSep 20, 2025Biogerontology

Melatonin may improve disrupted daily immune rhythms caused by aging and sleep loss in body and brain clocks of male rats

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Chronic total sleep deprivation significantly misaligned inflammatory marker expression rhythms in male Wistar rats aged 12 months and older.

Sleep deprivation elevated pro-inflammatory cytokines, particularly in the liver and cerebral cortex of middle-aged and old rats.
Older rats exhibited greater changes in inflammatory markers compared to younger rats, with the pattern being 24 months > 12 months > 3 months.
The liver and cerebral cortex were more affected by sleep deprivation than the suprachiasmatic nucleus, indicating they are more vulnerable to disruptions.
Melatonin treatment helped restore the rhythms of inflammatory markers, especially in the cerebral cortex and liver.
The suprachiasmatic nucleus demonstrated the highest resilience to sleep deprivation, confirming its role as the central circadian pacemaker.

AI simplified

Sleep deprivation (SD) and aging are linked to chronic inflammation, a contributor to age-associated diseases. Circadian rhythms, governed by suprachiasmatic nucleus (SCN), regulate immune and inflammatory responses. While aging and SD elevate pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, their impact on temporal dynamics of inflammation across tissues and age groups remains unclear. This study examines age-dependent effects of chronic total SD on daily expression rhythms of inflammatory markers in central (SCN) and peripheral (cerebral cortex, liver, intestine) clocks of male Wistar rats aged 3 (adult), 12 (middle-aged), and 24 (old) months (m). Nitric oxide (NO), linked to inflammation and metabolism, was also evaluated in liver and intestine. Animals were sampled at four Zeitgeber (ZT) times. Further, the study examined the effects of melatonin, a circadian-regulated antioxidant, anti-inflammatory agent, and sleep synchronizer, on daily rhythms of inflammatory markers with aging and upon SD were studied. The mRNA expression levels of rTnf-α, rIl-6 and rIl-1β were assessed using qRT-PCR. NO levels were measured using Griess assay. Rats were grouped as control, SD, SD + melatonin and vehicle control groups. Significant SD-induced misalignment, especially in rIl-6 and rTnf-α in cerebral cortex and liver was observed in 12 m. SD altered circadian phases and expression levels were significantly greater in older rats (24 m > 12 m > 3 m) and in peripheral clock as compared to central clock liver > cerebral cortex > intestine > SCN. Melatonin differentially restored these rhythms, most effectively for rIl-1β and in the cerebral cortex and liver. SCN showed highest resilience, reinforcing its role as the central circadian pacemaker, while the liver and cerebral cortex emerged as the most vulnerable to SD and aging.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗View full text (PDF) ↗

Abstract

Full Text

Related papers