Issue #13 -- October 2001. Pp. 48-51
New Systemic Hypothesis of Ageing
Copyright © by SORITES and Alexey Kolomiytsev
New Systemic Hypothesis of Ageing
Some functional features of complex multicellular organisms may not be explained by subcellular processes alone. These organisms function as complex systems, and the life of cells is determined both by molecular processes and system organization. This approach may represent the general idea about any living organism functioning and processes that influence the duration of life at all and persistence of pathologic conditions.
Our new hypothesis does not contradict either evolutionary or molecular theories of ageing. This is just an attempt to understand how ageing developed in complex organisms.
Multicellular organisms function as complex systems, and the life of cells is determined both by molecular processes and system organization. The developmental process is determined by kinetic curve of population growth (Khokhlov AN.,1987, Varfolomeev SD.,1990), which is typical for every cell association ( cell culture, colony of microorganisms, etc.) (Erbe W., et al., 1977, Foa P., et al., 1982, Bremer H., et al, 1983). It includes phases of induction, exponential growth, linear growth, deceleration, a stationary and atrophy phase.
The new hypothesis considers every multicellular organism as a system that consists of various cellular associations in symbiotic interaction. One of these associations dominates and determines the developmental kinetics of the whole organism.
The nervous system is the dominating cellular association in animals and human beings. The duration of its development is restricted by the capability of neurons to regenerate in adult organisms. This may determine the duration of life ofthe organism as a whole. So the organism is hypothetically presented as a «neuronal cell culture» that develops on the «medium» (the other tissues).
Although there is no nervous system in plants, this rule can also be observed in their organization. For instance, apical meristems in plants play the role of organogenesis units.
Because organs are produced continuously throughout the life cycle, the apical meristems maintain a pluripotent stem cell population (Bowman JL., 2000). Thus, apical meristems may play the dominating role in plant maintenance, development and life cycle.
Animal organisms (more exactly this applies to mobile animals and humans) may be hypothetically presented as a «neuronal cell culture» that develops on the «medium» -- the other functional units of organism.
Although there are certain reserves of neural stem cells in the human CNS, they are unable to generate new nerve cells in any useful amounts. This is an evolutionarily conditioned feature (Aubert I., et al., 1995, Olson L., 1997).
New stereological techniques (Cotter D., et al, 1999, Kubinova L., et al, 1999, West MJ., 1999) have failed to confirm earlier findings regarding age-associated neural loss (Regeur L., 2000) but there is the evidence of focal neural death and synaptic or receptor loss.
Recent researches in neurobiology revealed the ability of human neural stem cells «(1) to differentiate into cells of all neural lineages (i.e., neurons -- ideally to multiple subtypes, oligodendroglia, astroglia) in multiple regional and developmental contexts; (2) to self-renew (to give rise to new NSCs with similar potential); and (3) to populate developing and/or degenerating CNS regions» (Flax JD., et al. 1998, Brustle O., et al., 1998). The same features are essential in animal neural stem cells (Temple S., et al, 1999).
These features could be useful not only in treating neurodegenerative diseases (Brevig T., et al., 2000, Svendsen CN., et al., 1999) but also in a wider range of pathologic processes.
Constant alterations in neural tissue may lead to persistence of a number of pathologic processes and result in a decrease of life duration. The restoration of neural cells and their connections may be useful to modify the features of various chronic diseases and even increase life span.
New strategies including stem sells transplantation could be used for the stimulation of cell renewal processes in central and peripheral nervous system as a whole. This may result in continuous self-renovation of the whole organism as a complex system.
Moreover, epidermal growth factor (EGF) and transforming growth factor (TGF ) -- a member of the epidermal growth factor -- are essential components for a stable growth of neural cells (Junier MP., 2000). This may mean that these growth factors are necessary for both epithelial and neural tissues as ectoderm derivatives, and in one's turn the growth factors application could be one of possible ways to increase stability of neural cells of human organism.
Our hypothesis does not violate any of the existing theories of ageing. The theories of life span gene regulation may also be explained by means of our theory. Even cell division limit (Hayflick L., 1998, 2000) may be considered a compensatory feature that arose as a result of cellular development in complex systems where nutritional competition occurs as well as the destruction product accumulation.