Abstract
Data on the kinetics, peptide maps, induction and isoenzyme pattern of enzymes of rats show that functional changes in genes lead to aging in eukaryotes. Covalent modifications, such as acetylation and phosphorylation, of chromosomal proteins which are complexed with eukaryotic DNA to form the chromatin, decrease with age. Digestion of the chromatin DNA by the endonucleases, DNase I that cuts DNA at 10 base pair intervals and micrococcal nuclease (MCN) that cuts the linker DNA, were carried out to probe the conformational changes in chromatin. Whereas digestion by DNase I significantly decreases with age, the digestion by MCN does not. Thus the chromatin undergoes increasing compaction in non-dividing cells resulting in alterations in its fine structure. This leads to decreasing gene expression and progressive senescence.
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