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Violation of the regulation system

Database
Disorders of system regulation

Authors:

Investigations of this mechanism of aging were conducted by A. Moskalev, F. Wu, S. Imai and other scientists.

History:

Connection between disorders of system regulation and aging was revealed in the neuroendocrine theory of aging. Modern investigations confirm the presence of that correlation.

Example:

Numerous investigations made by Russian and American researches have shown that activation and suppression of certain genes in hypothalamus (a central neuroendocrine t regulator of the metabolism at the base of the brain) can slow down aging in the whole body.

Description:

Regulation of metabolism and homeostasis, as well as realization of system functions (respiration, excretion, digestion, blood circulation, immunity) is very essential. Its disturbance causes varied diseases and increases the probability of death. Simultaneously, all the regulatory processes mentioned above are exposed to age-dependent changes, and most of them are unfavorable. For example, the ability to maintain concentration of sugars, lipids and electrolyte in blood, concentration of hormones, blood pH, arterial pressure at a stable level is often lost while we age. Thus disorders of system regulations are key to aging understanding. Those disorders become apparent at early stages of aging, exacerbation of them hasten aging but counteraction to them decelerates aging.

Physiological regulation of all functions of our organism is under control of the nervous and endocrinous systems, and both of them change substantially during aging. Functioning of some brain regions (e.g. hypothalamus, hypophysis, epiphysis) become worse as an organism ages, and this has negative influence at the functions of peripheral endocrine glands (thyroid body, pancreatic gland, adrenal gland, gonads) and diffuse endocrine system. As the result, the level of many essential hormones goes beyond normal and beyond daily rhythmics, and that increases the risk of tens of diseases.

At a cell level, aging is also caused by disorders of regulation. A good half of all the proteins acting in the development of age-dependent pathologies and in longevity supporting is regulatory proteins. They be needed for signals perception and transferring among cells and from without. Hormonal shifts, disorders of intercellular communication and genetic instability cause changes in regulations of the activity of hundreds and thousands of genes. First of all, those are genes necessary for cell growth and divisions as well as for providing stress resistance.

Additions and Criticism:

Different endocrine glands have different rate of age-related changes. Some glands, e.g. thymus, reach maximum level of development early, and by puberty, their functions decline sharply. Most other endocrine glands reduce their intensity of functioning during aging only, and that reduction is usually gradual. At the same time, activity of vasopressin (neurohypophysial hormone) and gonadotropins (hormones of the anterior pituitary) increases as we mature and reduces in very advanced age only.

Publications:

  • Satoh, Akiko, and Shin-ichiro Imai. «Systemic regulation of mammalian ageing and longevity by brain sirtuins." Nature communications 5 (2014).
  • Matsumoto, A. M., et al. «Aging and the neuroendocrine regulation of reproduction and body weight." Experimental gerontology 35.9 (2000): 1251–1265.
  • Imai, Shin-ichiro, and Jun Yoshino. «The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing." Diabetes, Obesity and Metabolism 15.s3 (2013): 26–33.
  • Wu, Frederick CW, et al. «Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study." The Journal of Clinical Endocrinology & Metabolism 93.7 (2008): 2737–2745.