Gene silencing – a new theory of aging
Introduction
Theories about the mechanism of human aging have been proposed many times over the last 2000 years. And yet we still do not have a generally accepted and well-proven explanation for this universal phenomenon of life. Because aging consists of multiple events with a variety of causes, no one has been able to single out one predominant cause. Numerous theories have risen and then been cast aside as scientific knowledge increased. Some current theories center on a purported ‘master clock’ of aging. We do know that telomeres govern much of the aging program of individual cells (1). In addition, humans appear to possess another program for aging, one which includes methylation of promoter sequences of the genes and deacetylation of histones.
Section snippets
Silencing of genes during development and aging
Adult cells in the human body have an established methylation pattern in their DNA that is central to the aging program. But in the very first day of life the methylation pattern is erased. Most of the genes, which are silences later, are active during initial embryonal development. Then they begin to be blocked through methylation and deacetylation as their expression is no longer needed. Many genes are silenced after birth, including the genes for hemoglobin F. This trend accelerates
Supporting data and discussion
Differences in gene expression in various age groups were documented approximately 10 years ago [18], [19]. However, a number of studies in this area provided disappointing results, possibly due to lack of adequate technology. Introduction of DNA microarrays permitted determination of the levels of transcriptions of thousands of genes simultaneously and confirmed different patterns of gene expression during development and aging (20). A new DNA methylation technology allowed detection of
Future prospects and conclusion
Research done by others indicates many genes are silenced during aging and development. Additional evidence comes from observation of the silencing of genes for hemoglobin F. This is the primary hemoglobin in the developing fetus after the first 10 weeks of fetal life. Adult hemoglobin A becomes the main hemoglobin within 18–24 weeks after birth. Hemoglobin F production falls dramatically after birth and practically stops within 1 year. During this process the hemoglobin F genes are silenced
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