Aging of the Mammalian Circadian Timing System: Changes in the Central Pacemaker and Its Regulation by Photic and Nonphotic Signals

Abstract

Aging alters many aspects of endogenously regulated, 24-hour (circadian) rhythms, such as their amplitude, relationship to the ambient lighting cycle, and sensitivity to phase resetting signals. In order to elucidate the mechanisms responsible for these age-related changes, many studies have investigated age-related changes in the neural components of the circadian timing system, which include the hypothalamic suprachiasmatic nucleus (SCN), the site of the mammalian master circadian pacemaker, its afferent projections from the retina, thalamus, and midbrain raphe, and its efferent projections to the hypothalamus, thalamus and limbic system. Studies have shown that the SCN exhibits age-related changes in electrical activity rhythms in the absence of neurodegeneration. Also, aging selectively decreases SCN expression of the circadian clock genes, Clock and Bmal1, as well as vasoactive intestinal peptide. The latter participates in mediating light-induced phase resetting of the circadian pacemaker and the amplitude of the preovulatory luteinizing hormone surge, which are both attenuated by aging. Furthermore, by decreasing serotonin 5-HT₇ receptors in the dorsal raphe, aging reduces one type of nonphotic input to the SCN. This review describes which aspects of circadian rhythm regulation exhibit changes during aging, as well as which mechanisms appear to be spared or remain to be explored.

Influence of aging on Bmal1 and Per2 expression in extra-SCN oscillators in hamster brain

“…Aging deleteriously affects the expression of circadian rhythms (see (Duncan, 2007; Monk, 2005) for review). The most consistent and prominent age-related change is an attenuation of the amplitude and robustness of rhythms; in some cases fragmentation or loss of rhythms occurs.…”

The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5‐HT1B receptors

“…During aging, circadian rhythms exhibit many alterations, including reduced amplitude, attenuation of photic and nonphotic phase shifts, increased fragmentation, and dysynchrony (for review, see Duncan, 2007). These changes are associated with age-related changes in the central circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN), including reduction in vasoactive intestinal peptide (VIP) mRNA, and augmentation of serotonin (5-hydroxytryptamine; 5-HT) 1B receptors and serotonin transporters (Krajnak et al, 1998a;Duncan et al, 2000Duncan et al, , 2001.…”

Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice

“…Generally, aging is associated with reduced amplitudes among these daily rhythms; the most severe changes are associated with Alzheimer's disease (AD) (2). Circadian disorders affect more than 80% of individuals over age 65 (3) because of several converging factors; loss of neurons in the suprachiasmatic nucleus, decreased melatonin and melatonin receptor sensitivity, and minimal zeitgebers because of lifestyle all contribute to circadian dysfunction (1,4).…”