Life Extension - Pathology
Samurai Law of Biology (Better Dead then Wrong) -
updated: 16 December 2008
Mitochondria in the programmed death phenomena; a principle of biology: "it is better to die than to be wrong".
IUBMB Life. 2000 May;49(5):365-73
Skulachev VP.
The very fact that mitochondria participate in amplification of the cell suicide signals has stimulated interest in the mechanism of this and related phenomena. It seems probable that mitochondria possess an autonomic system that allows them to commit suicide. This mitoptosis is mediated by reactive oxygen species (ROS), causing opening of the permeability transition pores (PTP) in the inner mitochondrial membrane. Mitoptosis can purify the mitochondrial population in a cell from the ROS-overproducing organelles. Massive mitoptosis can result in apoptosis (programmed cell death) because of the release of proapoptotic proteins from the mitochondrial intermembrane space, a mechanism purifying tissues from the ROS-overproducing and other unwanted cells. Large-scale apoptosis can be used by organisms to eliminate some organs during ontogenesis (organoptosis). In adult organisms, organoptosis of organs of vital importance may entail a programmed death of individuals (phenoptosis). This mechanism might purify kins, communities, and populations from individuals becoming dangerous because of, for example, heavy infection (septic shock). It is hypothesized that aging represents a slow ROS-linked phenoptosis that eliminates individuals with damaged genomes and gives reproductive advantage to those who succeeded in a better preservation of their genomes from damage.
Publication Types:
Online - Abstract
The programmed death phenomena, aging, and the Samurai law of biology
Exp Gerontol. 2001 Jul;36(7):995-1024
Skulachev VP.
Analysis of the programmed death phenomena from mitochondria (mitoptosis) to whole organisms (phenoptosis) clearly shows that suicide programs are inherent at various levels of organization of living systems. Such programs perform very important functions, purifying (i) cells from damaged (or unwanted for other reasons) organelles, (ii) tissues from unwanted cells, (iii) organisms from organs transiently appearing during ontogenesis, and (iv) communities of organisms from unwanted individuals. Defence against reactive oxygen species (ROS) is probably one of primary evolutionary functions of programmed death mechanisms. So far, it seems that ROS play a key role in the mito-, apo-, organo- and phenoptoses. Here a concept is described which tries to unite Weismann's concept of aging as an adaptive programmed death mechanism and the alternative point of view considering aging as an inevitable result of accumulation in an organism of occasional injuries. It is suggested that injury accumulation is monitored by special system sending a death signal to actuate a phenoptotic program when the number of injuries reaches some critical level. The system in question is organized in such a way that the lethal case appears to be a result of phenoptosis long before occasional injuries make the functioning of the organism impossible. This strategy is supposed to prevent the appearance of asocial monsters capable to ruining kin, community and entire population. These relationships are regarded as an example of the Samurai law of biology: 'It is better to die than to be wrong'. It is stressed that for humans these cruel regulations look like an atavism that should be overcome to prolong the human life span.
Publication Types:
Online - Abstract
Programmed death phenomena: from organelle to organism
Ann N Y Acad Sci. 2002 Apr;959:214-37
Skulachev VP.
Programmed death phenomena appear to be inherent not only in living cells (apoptosis), but also in subcellular organelles (e.g., self-elimination of mitochondria, called mitoptosis), organs (organoptosis), and even whole organisms (phenoptosis). In all these cases, the "Samurai law of biology"--it is better to die than to be wrong--seems to be operative. The operation of this law helps complicated living systems avoid the risk of ruin when a system of lower hierarchic position makes a significant mistake. Thus, mitoptosis purifies a cell from damaged and hence unwanted mitochondria; apoptosis purifies a tissue from unwanted cells; and phenoptosis purifies a community from unwanted individuals. Defense against reactive oxygen species (ROS) is probably one of the primary evolutionary functions of programmed death mechanisms. So far, it seems that ROS play a key role in the mito-, apo-, organo-, and phenoptoses, which is consistent with Harman's theory of aging. Here a concept is described that tries to unite Weismann's hypothesis of aging as an adaptive programmed death mechanism and the generally accepted alternative point of view that considers aging as an inevitable result of accumulation in an organism of occasional injuries. It is suggested that injury accumulation is monitored by a system(s) actuating a phenoptotic death program when the number of injuries reaches some critical level. The system(s) in question are organized in such a way that the lethal case appears to be a result of phenoptosis long before the occasional injuries make impossible the functioning of the organism. It is stressed that for humans these cruel regulations look like an atavism that, if overcome, might dramatically prolong the human life span.
Publication Types:
Online - Abstract
Aging as a mitochondria-mediated atavistic program: can aging be switched off?
Ann N Y Acad Sci. 2005 Dec;1057:145-64
Skulachev VP, Longo VD.
Programmed death phenomena have been demonstrated on subcellular (mitoptosis), cellular (apoptosis), and supracellular (collective apoptosis) levels. There are numerous examples of suicide mechanisms at the organismal level (phenoptosis). In yeast, it was recently shown that the death of aging cells is programmed. Many of the steps of programmed cell death are shown to be common for yeast and animals, including mammals. In particular, generation of the mitochondrial reactive oxygen species (ROS) is involved in the suicide programs. Aging of higher animals is accompanied by an increase in damage induced by mitochondrial ROS. Perhaps prevention of such damage by scavenging of mitochondrial ROS might slow down or even switch off the aging programs.
Publication Types:
Online - Abstract
Programmed death phenomena: from organelle to organism
Ann N Y Acad Sci. 2002 Apr;959:214-37
Skulachev VP.
Programmed death phenomena appear to be inherent not only in living cells (apoptosis), but also in subcellular organelles (e.g., self-elimination of mitochondria, called mitoptosis), organs (organoptosis), and even whole organisms (phenoptosis). In all these cases, the "Samurai law of biology"--it is better to die than to be wrong--seems to be operative. The operation of this law helps complicated living systems avoid the risk of ruin when a system of lower hierarchic position makes a significant mistake. Thus, mitoptosis purifies a cell from damaged and hence unwanted mitochondria; apoptosis purifies a tissue from unwanted cells; and phenoptosis purifies a community from unwanted individuals. Defense against reactive oxygen species (ROS) is probably one of the primary evolutionary functions of programmed death mechanisms. So far, it seems that ROS play a key role in the mito-, apo-, organo-, and phenoptoses, which is consistent with Harman's theory of aging. Here a concept is described that tries to unite Weismann's hypothesis of aging as an adaptive programmed death mechanism and the generally accepted alternative point of view that considers aging as an inevitable result of accumulation in an organism of occasional injuries. It is suggested that injury accumulation is monitored by a system(s) actuating a phenoptotic death program when the number of injuries reaches some critical level. The system(s) in question are organized in such a way that the lethal case appears to be a result of phenoptosis long before the occasional injuries make impossible the functioning of the organism. It is stressed that for humans these cruel regulations look like an atavism that, if overcome, might dramatically prolong the human life span.
Publication Types:
Online - Abstract
Publication Types:
|
