Genetic, epigenetic and posttranslational mechanisms of aging.
Gerontological experimentation is and was always strongly influenced by "theories". The early decades of molecular genetics inspired deterministic thinking, based on the "Central Dogma" (DNA --> RNA --> Proteins). With the progress of detailed knowledge of gene-function a much more complicated picture emerged. Regulation of gene-expression turned out to be a highly complicated process. Experimental gerontology produced over the last decades several "paradigms" incompatible with simple genetic determinism. The increasing number of such detailed experimental "facts" revealed the importance of epigenetic factors and of posttranslational modifications in the age-dependent decline of physiological functions. We shall present in this review a short but critical analysis of genetic and epigenetic processes applied to the interpretation of the more and more precisely elucidated experimental paradigms of aging followed by some of the most relevant aging-mechanisms at the post-translational level, the posttranslational modifications of proteins such as the Maillard reaction, the proteolytic production of harmful peptides and the molecular mechanisms of the aging of elastin with the role of the age-dependent uncoupling of the elastin receptor, as well as the loss of several other receptors. We insist also on the well documented influence of posttranslational modifications on gene expression and on the role of non-coding RNA-s. Altogether, these data replace the previous simplistic concepts on gene action as related to aging by a much more complicated picture, where epigenetic and posttranslational processes together with environmentally influenced genetic pathways play key-roles in aging and strongly influence gene expression.
Robert
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L
Hôpital Hôtel Dieu, Université Paris, France. lrobert5@wanadoo.fr
Labat-Robert
J
J
Robert
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AM
D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005853:Geriatrics; D006801:Humans; D015416:Maillard Reaction; D018384:Oxidative Stress; D010455:Peptides / Q000009:adverse effects / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism
D010455:Peptides; D022661:RNA, Untranslated; D004549:Elastin