Melatonin Secretion and Muscle Strength in Elderly Individuals: A Cross-Sectional Study of the HEIJO-KYO Cohort

There is growing evidence that higher levels of inflammatory markers are associated with physical decline in older persons, possibly through the catabolic effects of inflammatory markers on muscle. The aim of this study was to investigate the association between serum levels of inflammatory markers and loss of muscle mass and strength in older persons. Using data on 2,177 men and women in the Health, Aging, and Body Composition Study, we examined 5-year change in thigh muscle area estimated by computed tomography and grip and knee extensor strength in relation to serum levels of interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), and soluble receptors (measured in a subsample) at baseline. Higher levels of inflammatory markers were generally associated with greater 5-year decline in thigh muscle area. Most associations, with the exception of soluble receptors, were attenuated by adjustment for 5-year change in weight. Higher TNF-alpha and interleukin-6 soluble receptor levels remained associated with greater decline in grip strength in men. Analyses in a subgroup of weight-stable persons showed that higher levels of TNF-alpha and its soluble receptors were associated with 5-year decline in thigh muscle area and that higher levels of TNF-alpha were associated with decline in grip strength. TNF-alpha and its soluble receptors showed the most consistent associations with decline in muscle mass and strength. The results suggest a weight-associated pathway for inflammation in sarcopenia.

Melatonin is a highly evolutionary conserved endogenous molecule that is mainly produced by the pineal gland, but also by other nonendocrine organs, of most mammals including man. In the recent years, a variety of anti-inflammatory and antioxidant effects have been observed when melatonin is applied exogenously under both in vivo and in vitro conditions. A number of studies suggest that this indole may exert its anti-inflammatory effects through the regulation of different molecular pathways. It has been documented that melatonin inhibits the expression of the isoforms of inducible nitric oxide synthase and cyclooxygenase and limits the production of excessive amounts of nitric oxide, prostanoids, and leukotrienes, as well as other mediators of the inflammatory process such as cytokines, chemokines, and adhesion molecules. Melatonin's anti-inflammatory effects are related to the modulation of a number of transcription factors such as nuclear factor kappa B, hypoxia-inducible factor, nuclear factor erythroid 2-related factor 2, and others. Melatonin's effects on the DNA-binding capacity of transcription factors may be regulated through the inhibition of protein kinases involved in signal transduction, such as mitogen-activated protein kinases. This review summarizes recent research data focusing on the modulation of the expression of different inflammatory mediators by melatonin and the effects on cell signaling pathways responsible for the indole's anti-inflammatory activity. Although there are a numerous published reports that have analyzed melatonin's anti-inflammatory properties, further studies are necessary to elucidate its complex regulatory mechanisms in different cellular types and tissues. © 2012 John Wiley & Sons A/S.

Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day-night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated (but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension.