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Failure of the internal clock

Database
Disorders of the internal clock

Authors:

This mechanism of aging is investigated by v. Pouthas, M. J. Allman, O. v. Reeth et al.

History:

The earliest known account of a circadian process dates from the 4th century BC, when Androsthenes, a ship captain serving under Alexander the Great, described diurnal leaf movements of the tamarind tree. The observation of a circadian or diurnal process in humans is mentioned in Chinese medical texts dated to around the 13th century. The first recorded observation of an endogenous circadian oscillation was by the French scientist J.-J. d’Ortous de Mairan in 1729 when he studied the movement of the leaves of the plant Mimosa pudica. In 1918, J. S. Szymanski showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature. R. Konopka and S. Benzer isolated the first clock mutant in Drosophila in the early 1970s and mapped the «period» gene, the first discovered genetic component of a circadian clock. Joseph Takahashi discovered the first mammalian «clock gene» using mice in 1994. The term «circadian» was coined by F. Halberg in the late 1950s.

Example:

Disorders of the internal clock predispose our organism to system inflammation, cancer, cardiovascular diseases, metabolic syndrome and diabetes, neurodegenerative, cognitive and sleep disorders.

Some acute pathologies like hypertensic crisis, myocardial infarction, attacks of asthma and allergy are sometimes linked to the definite day hours.

Description:

Internal body clock, or circadian rhythms are the cyclic oscillation of the intensity of various biological processes which is linked to alternation of day and night. Although circadian rhythms are connected with external stimuli, they have endogenous origin. The central (in the brain) and peripheral (in liver, lungs, heart, kidneys, skin) internal body clocks play important role in the regulation of the metabolism, sleep/wake cycles, rhythmicity of the hormones secretion, physical activity, intestinal peristalsis, body temperature, arterial pressure and levels of various metabolites in the blood.

Circadian rhythms disorders cause oxidative stress, disorders in synthesis of regulatory and other proteins, lead to inflammatory processes, insensibility to insulin, hormonal disbalance. Mistiming between the internal clock and environmental signals leads to the onset of the symptoms of tiredness, disorientation, sleeplessness, as well as to deterioration in the general level of health.

Additions and Criticism:

Tests on laboratory animals have shown that the activity of key genes controlling circadian rhythms comes down as an individual grows older. Thus, mice with mutations reducing activity of the key genes mentioned above live substantially less than normal animals. At the same time, artificial activation of some of those genes in the muscle tissue of mice leads to lifespan extension. Similar results were obtained in researches on fruit flies.

Finally, we can resume that circadian rhythms disorders conform with three characteristics of the criterion acceptable for aging detection: their appearance may be observed at the early stage of aging; such disorders promote aging; but if we prevent them, aging may be delayed.

Publications:

  • Baudouin, Alexia, et al. «Differential involvement of internal clock and working memory in the production and reproduction of duration: A study on older adults." Acta Psychologica 121.3 (2006): 285–296.
  • Allman, Melissa J., et al. «Properties of the internal clock: first-and second-order principles of subjective time." Annual review of psychology 65 (2014): 743–771.
  • Perbal, Séverine, et al. «Effects of internal clock and memory disorders on duration reproductions and duration productions in patients with Parkinson’s disease." Brain and cognition 58.1 (2005): 35–48.
  • Turek, Fred W., et al. «Effects of age on the circadian system." Neuroscience & Biobehavioral Reviews 19.1 (1995): 53–58.