St. Petersburg ProceedingsThe programmed death phenomena, aging, and the Samurai law of biology
Introduction
For aerobic organisms, molecular oxygen always creates a problem because it is a precursor of so-called reactive oxygen species (ROS). Among these the hydroxyl radical (OH·) is the most dangerous since thermodynamically it can oxidize any compound of biological origin (redox potential, +1.35 V), the activation energies for such oxidations being very low. Oxidation of DNA is of especially dramatic consequence due to damage to genetic information. This is why biological evolution invented a multilevel system of the anti-oxygen defence that strongly reduces the danger of oxygen.
Recent progress in cell biology studies has clearly revealed that programmed death mechanisms are actuated when other lines of defence fail to solve the problem (for reviews, see Skulachev, 1996a, Skulachev, 1996b, Skulachev, 2000a). This situation represents a particular case of a general biological principle that I called the Samurai law of biology: ‘It is better to die than to be wrong’. According to this principle, a living system insures itself against degradation of genetic and other very complicated programs developed during perhaps more than three billion years of biological evolution. The Samurai law means that a living system is always ready to commit suicide. It kills itself when recognizes that it has become useless or even dangerous for a living system of a higher hierarchical position (Skulachev, 2000a).
Below I shall describe how the programmed death phenomena at various levels of complexity (from intracellular organelles to living organisms) help overcome the oxygen danger and solve some other problems. This analysis will be concluded by an attempt to apply the Samurai law to the processes of aging.
Section snippets
Mitochondrial antioxidant system: initial lines of defence.
Mitochondria, the respiring organelles of the cell, have a large amount of electron transfer enzymes that can be attacked by O2. The one-electron reduction of O2 to O2·− is usually followed by conversion of O2·− to H2O2, which is an immediate precursor of OH·, the most dangerous member of the ROS family. As a rule, mitochondria are responsible for the production of most of the ROS generated in the cell. This occurs in spite of that mitochondria are well equipped to prevent ROS formation and to
Apoptosis induced by massive mitoptosis
As mentioned in the preceding section, the ROS-induced PTP opening leads to swelling of the matrix and, consequently, to the loss of integrity of the outer mitochondrial membrane, thus releasing the intermembrane proteins into the cytosol. Among them, the following four proteins are of interest in this context: cytochrome c, apoptosis-inducing factor (AIF), the second mitochondrial apoptosis-activating protein (Smac; also abbreviated DIABLO) and procaspase 9. All these proteins are somehow
Organoptosis, programmed elimination of unwanted organs.
Massive apoptosis of cells composing an organ should eliminate the organ. This process can be defined as ‘organoptosis’. As an example, consider the disappearance of the tail of a tadpole when it converts to a frog. It was recently reported (Kashiwagi et al., 1999) that addition of thyroxine (a hormone known to cause regression of the tail in tadpole) to severed tails surviving in a special medium caused shortening of the tails that occurred on the time scale of hours. The following chain of
Definition
Obviously, massive apoptosis in an organ of vital importance, resulting in organoptosis, must entail death of the entire organism. On the face of it, such an event should be regarded as a lethal pathology of no biological sense. However, it may not be the case if the organism in question is a member of a kin or community of other individuals. Here, altruistic death of individuals may appear to be useful for a superorganismal unit, being a mechanism for adaptation of the group to a changing
Some general remarks
Weismann's (1889)hypothesis on aging as an adaptive mechanism was strongly criticized by Medawar (1952), who assumed that aging could not have developed during the course of biological evolution. Medawar in fact assumed that, under natural conditions, the majority of organisms die before they become old. This assumption, however, cannot be applied to some periods of evolution of many species (Bowles, 2000).
Moreover, individuals with changes in their genomes can dramatically affect the fate of a
End-under-replication of linear DNA. Role of the telomere
Bowles (1998) suggested that, historically, the living cell invented the first specialized mechanism of aging when linear DNA substituted for the circular DNA inherent in the majority of bacteria and Archae. This event immediately resulted in a specific kind of DNA aging, a process consisting of replication-linked shortening of DNA. Such shortening inevitably accompanies replication of linear DNA, since even now the replication complex operates with linear DNA in the same way as it does with
Specific features of human aging
In many animal species including higher monkeys, the females die soon after their reproductive period is over, a fact that can be regarded as one more example of phenoptosis.
Humans are unique in they have a lifespan that is twice as long as other primates. This is due to the fact that the post-reproductive age life of the female is strongly extended. Lewis (1999) proposed that ‘the transmission of knowledge from grandparents to progeny serves as a driving force for extending human longevity...
Conclusions
In this paper, we started with programmed death of intracellular organelles, then considered similar phenomena on the levels of cells and organs and, moving along this line, came to phenoptosis, programmed death of an organism. The latter for sure takes place in wild nature, being inherent in quite different species from bacteria to higher animals. The possibility has been discussed that phenoptosis also occurs among humans. Here septic shock was regarded as an example of fast phenoptosis
Acknowledgements
The author is very grateful to the Ludwig Institute for Cancer Research (Grant RBO 863) and the Russian Foundation for Basic Research (Grants 95-15-00022 and 00-15-97799) for support.
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