LINEBURG


<< . .

 10
( 10)



OF AGING AND THE CONTROL OF BIOLOGICAL
TIME DURING INDIVIDUAL DEVELOPMENT
A. M. Olovnikov
Institute of Biochemical Physics, Russian Academy of Sciences,
ul. Chernyakhovskogo, 5 – 94, Moscow 125319, Russia;
E mail: olovnikov@dol.ru
Received September 1, 2002

The redusome hypothesis of aging and the control of biological time in individual development is proposed.
Redusomes are hypothetical perichromosomal particles arising in differentiation events during morphogenesis of an
organism. The linear molecule of DNA covered with proteins in redusome is assumed to be the copy of a segment of
the chromosomal DNA. Redusomes are located mainly in subtelomeric regions of chromosomes. The redusome does
not leave a body of chromosome even in the course of cellular divisions, being kept in its chromosomal nest. Like
telomeric DNA, a redusome linear DNA is shortened step by step. Thus, tiny redusomes progressively decrease in
sizes; it is from here their name originates. Together with loss of the length of DNA in a redusome, the number of dif
ferent genes contained in it also decreases. Shortening of the redusomal DNA molecules (and, coupled to it, changes
of the sets of genes in redusomes) is responsible for age dependent shifts in the level of expression of different chro
mosomal genes. Owing to this, redusome DNA shortening serves as a key means of measuring biological time in indi
vidual development. The main part of DNA of most redusomes is postulated to be occupied by non coding genes.
Low molecular weight RNAs (micro RNAs and fountain RNAs, or fRNAs) are transcribed from them. These RNAs
are involved in regulation of various chromatin repackings that are specific to certain differentiations, while others
modulate the levels of expression of chromosomal genes. Hypothetical «fountain» RNAs can quantitatively regulate
the expression levels of chromosomal genes, forming specific complexes with fions. Fions are suggested to be specif
ic sites of a chromosomal DNA which are complementary to different fRNAs. Fions reside in the vicinity of usual
chromosomal genes. A complex of the fRNA fion, specifically interacting with a closed gate of the corresponding
ionic channel of the internal nuclear membrane, initiates the opening of the gate for a very short term, thus organiz
ing activity of an ion fountain which appears to be automatically aimed at the chromosomal gene nearest to the fion
involved. The ion fountain creates, depending on specificity of matching fRNA, fion and ionic channel, distinctive
ionic environment near the certain structural genes. Ionic fountains exert their action on the configuration of corre
sponding segments of chromatin and on the transcriptional efficiency of chromosomal genes in a topographically spe
cific manner. Hence, the fountain system of nucleus is able to regulate the quantitative traits both of cells and organ
ism; it can control dominance of alleles and plays a role in individual development. Significant and escalating trun
cation of the redusome DNA causes cell aging due to an arising and increasing deficit of fRNAs and, for this reason,
the lack of required ions near certain structural genes. Progressive shortening of DNA of redusomes is proposed to
result in cellular aging because of a constantly growing shortage of low molecular weight RNAs transcribed from
redusomal genes. Two types of redusomes are postulated: chronosomes and printosomes. Linear molecules of DNA
in these two types of redusomes are called chronomeres and printomeres, respectively. Chronosomes are responsible
for measurement of biological time in non dividing cells of the CNS. Printosomes remember positions of cells in the
course of interpretation of the positional information in morphogenesis. In accordance with the position of a cell in
morphogenetic field, printomeres do change cellular properties and remember the change made (this is a so called
printomere mechanism of interpretation of the positional information). Besides, printomeres participate in main
taining the achieved state of cellular differentiation. Normally chronomere is shortened only on the maximum of
infradian hormonal rhythm ( rhythm) which initiates the act of a superhigh velocity of its transcription that is fin
ished with truncation of the end of a chronomere (effect called scrupting).The printomere can be shortened due to
the effect of DNA end underreplication and owing to scrupting. The effect of the end underreplication of DNA in
doubling cells occurs simultaneously both in printomeres and telomeres. Shortening of telomeres is just a bystander
process of aging of cells, whereas a true cause of biological aging is only the shortening of a redusome DNA.
Processing of certain redusomes in terminally differentiating cells is a cause of a proliferation arrest. Linkage of genes
in a eukaryotic chromosome is determined by the distances between genes and redusomes.
Key words: telomere, transcription, aging, biological time, ions, biological rhythms, differentiation, linkage of genes




68 . 1 2003

<< . .

 10
( 10)



Copyright Design by: Sunlight webdesign