Circadian clock aging

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Circadian clock aging

In mammals, the central circadian clock is a cellular mechanism found in the hypothalamic suprachiasmatic nuclei (SCN). Photic information is perceived by the retina and transmitted to the SCN via the retinohypothalamic tract (RHT). Synchronization of SCN cells leads to coordinated circadian outputs that regulate peripheral rhythms.

The circadian clock controls a wide array of physiological and behavioral systems, including energy metabolism, gastrointestinal tract motility, sleep-wake cycles, cardiovascular activity, endocrine secretion, body temperature, renal activity, and locomotor activity. This control is emphasized by timed manifestations of certain pathologies, such as hypertensive crises, myocardial infarction, and asthma and allergy attacks. Disruption of the coordination between the endogenous clock and the environment leads to symptoms of fatigue, disorientation, and insomnia as seen in jet-lagged travelers or altered hormone profiles and high morbidity as seen in shift workers. Moreover, disruption of circadian rhythms can seriously impact overall health and increase cancer proneness.

In mammals, the aging process leads to major alterations in output rhythms of the circadian clock. These changes include a shift in the phase and decrease in amplitude. In humans, aging is associated with a phase advance in melatonin secretion and body temperature rhythms. Indeed, unlike young human subjects, older individuals typically show earlier habitual time of sleeping and waking alongside disturbed sleep. The mechanisms leading to the aging-related alterations are largely unknown, but they are paralleled by changes in the neurochemical and electrophysiological output of the SCN with no change in cell number or size. For example, SCN shows alterations in the expression of vasoactive intestinal polypeptide (VIP), arginine vasopressin (AVP), and transforming growth factor beta (TGF-β) as well as a reduction in the amplitude of rhythmic electrical activity.

The circadian clock in mammals regulates metabolism by mediating the expression and/or activity of certain metabolic enzymes, hormones, and transport systems. A large number of nuclear receptors involved in lipid and glucose metabolism has been found to exhibit circadian expression. The rhythmic expression and activity of the metabolic pathways is mainly attributed to the robust and coordinated expression of clock genes in the liver and adipose tissue