The main factors acting in aging process and the functional relationship between them.
The aging of higher organisms is multi-factorial process. It is influenced and modified by various genetic, biochemical, regulation and other systems working at once in close contact. Each system can make direct impact on aging process or act indirectly (e.g. through other pathway). That is why interaction between mentioned systems is important too. Here we have tried to overview the influence of each factor to the aging process and to discuss how all mentioned aging-factors could act as the whole complex.
Mitochondriae are the main unit of chemical power supply in the cell. During the synthesis of macroergical bio-molecules free radicals are being produced as the by-product. Free radicals when released in large quantities cause intercellular oxidative stress (e.g. oxidative damage of DNA, proteins and other bio-molecules). Oxidative stress is the main reason of accelerated senescence. Free radicals can result tissue degeneration by damaging mitochondria genome and cause early apoptosis (programmed cell death) through the damage of nuclear genome. Endogenous oxidative damage and repair systems play a big role in spontaneous mutagenesis. Mutated genes usually encode nonfunctional products, which disturb biochemical or/and signaling pathways leading to more or less expressed pathological state. Free radicals attack proteins and modify them. It usually disturbs protein function and can accelerate the aging process.
Cell cycle is regulated by different specific proteins. At this moment we know lots of different proteins which regulate cell cycle, phase change (cancer supressors, cyclins, and MAP kinases). When these proteins are damaged by mutations cell cycle regulation can be disturbed. Cells could die or become not controlled depending on the nature of mutation- this could lead to cancer. Cell cycle regulation disorders leads to accelerated aging and/or cell malignancy.
We know genes concerned with pathological aging. When they are damaged organism ages much faster. These genes are named gerontogenes - aging genes. Genetic polymorphisms (determining individual's longevity) are found. The existence of longevity gene is still very real. Some age linked diseases are known in medical practice (Werner's, Bloom's, Cocaine's syndromes, progery and other). Patents had damaged various gerontogenes. It was observed that these genes encoded replication, transcription and repair machinery components of the cell.
Telomeres are the terminal parts of eukaryotic chromosomes. The influence to aging of telomeres is highly discussed. They are called "molecular clock" of the cell. Cell division times are correlated with telomere length. After each cell division telomeres get shorter. When telomere shortens to the critical stage, the intensity of cell division significantly decreases, and then cell differentiates and ages. Telomeres are persistent in the not aging cells: cancer and germ line.
The influence of transcription, translation and posttranslational modification systems to the cell is not static but highly regulated. For example, when synthesized protein is modified incorrectly (wrong phosphorylation) its function alters. If protein function is important, appropriate intracellular processes or regulation could be disturbed. Such errors lower vitality of organism and accelerate aging.
Intracellular processes are accordant and rigorous; it means cell is highly organized and integrated system. Information (signal transduction) and the regulation of bioprocess are the main players in the development and the maintenance of this system and aging. When mutations or modification disturb proteins/genes of signal systems, signal transduction and other bioprocesses proceed abnormally. We should not forget that organism is integrated system and all factors mentioned above act in-between with others. Mitochondrial metabolism process stimulates oxidative damage, but each cell has repair systems defeating it (reparative systems, apoptosis, etc.).
Aging is a natural process, living organisms are highly adapted to the laws of nature, and senescent cells are being changed with juvenile. The existence of not differentiated stem cells in every living organism has a deep meaning; they act as a depot in the regeneration of damaged cells.
In the higher organisms, aging and renovation process is strictly regulated, anyway the source of aging and renovation signal are of material nature (biomolecules), which, changes during the life cycle. Because of these changes (modifications and mutations) organism necessarily lose its battle with aging.
The whole survey is now available on Innovita Research Foundation web site.