ABSTRACT
Melatonin is produced in numerous mammalian organs and cells, but the circulating hormone is mostly secreted by the pineal gland (Hardeland et al. 2011), with a prominent maximum at night. The nocturnal peak undergoes age-dependent changes (Waldhauser et al. 1993). A normal decline observed during youth is explained by a dilution effect due to the growth of the body in the absence of substantial changes in pineal secretion. However, decreases at advanced age reect decits in melatonin formation, which can be related to a dysfunction of the circadian master clock, the suprachiasmatic nucleus (SCN), which steers pineal activity or signal transmission from the retina via SCN to the pineal gland (Hardeland et al. 2012). However, the aging-related changes have turned out to be interindividually highly variable (Hardeland 2012a). Persons over 60 years may display almost normal nocturnal peaks or, in other cases, may have lost a robust melatonin rhythm. Moreover, the melatonin maximum is frequently phase-advanced in elderly subjects relative to younger ones (Skene and Swaab 2003). However, melatonin levels may be even more decreased in a number of diseases and disorders (summarized by Hardeland et al. 2011; Hardeland 2012a,b). As will be discussed next, these include metabolic diseases, pain and stressful conditions, and, especially, but with exceptions, neurodegenerative diseases. Sleep disturbances can be an indicator of a disturbed melatonin rhythm, which may be corrected by melatonergic treatment (Srinivasan et al. 2009). The changes caused by diseases and disorders may be transient or permanent. Permanently reduced levels of circulating melatonin appear to be stronger predictors of a diseased state than of aging per se. This chapter will analyze the conditions under which melatonin is decreased and discuss the options of treatments as well as their limits.
