Receptor regulation of senile phenoptosis

• Published in: Biochemistry (Moscow) Vol. 79; no. 10; pp. 994 - 1003
• Main Authors: Skulachev, M. V., Severin, F. F., Skulachev, V. P.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-10-2014; Springer; Springer Nature B.V
• Subjects: Aging; Aging - physiology; Ambient temperature; Amino acids; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Caenorhabditis elegans - physiology; Caloric Restriction; Carbohydrates; Cell research; Cold Temperature; Diabetes; Diet; Dietary Proteins - administration & dosage; Eating; Food; Humans; Hypothesis; Life Sciences; Life span; Low temperature; Macaca mulatta; Methionine - administration & dosage; Methionine - blood; Microbiology; Mortality; Nociceptors - physiology; Oxidative stress; Signal Transduction; Starvation; Russia; food restriction; aging program regulation; aging; diabetes; phenoptosis
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297914100022

Here we present a concept that considers organism aging as an additional facultative function promoting evolution, but counterproductive for an individual. We hypothesize that aging can be inhibited or even arrested when full mobilization of all resources is needed for the survival of an individual. We believe that the organism makes such a decision based on the analysis of signals of special receptors that monitor a number of parameters of the internal and external environment. The amount of available food is one of these parameters. Food restriction is perceived by the organism as a signal of coming starvation; in response to it, the organism inhibits its counterproductive programs, in particular, aging. We hypothesize that the level of protein obtained with food is estimated based on blood concentration of one of the essential amino acids (methionine), of carbohydrates — via glucose level, and fats — based on the level of one of the free fatty acids. When the amount of available food is sufficient, these receptors transmit the signal allowing aging. In case of lack of food, this signal is cancelled, and as a result aging is inhibited, i.e. age-related weakening of physiological functions is inhibited, and lifespan increases (the well-known geroprotective effect of partial food restriction). In
Caenorhabditis elegans
, lowering of the ambient temperature has a similar effect. This geroprotective effect is removed by the knockout of one of the cold receptors, and replacement of the
C. elegans
receptor by a similar human receptor restores the ability of low temperature to increase the lifespan of the nematode. A chain of events linking the receptor with the aging mechanism has been discovered in mice — for one of the pain receptors in neurons, the nerve endings of which entwine pancreas β-cells. Age-related activation of these receptors inhibits the work of insulin genes in β-cells. Problems with insulin secretion lead to oxidative stress, chronic inflammation, and type II diabetes, which can be regarded as one of the forms of senile phenoptosis. In conclusion, we consider the role of some psychological factors in the regulation of the aging program.