Aging of the Genome: The Dual Role of DNA in Life and Death
Aging has long since been ascribed to the gradual accumulation of DNA mutations in the genome of somatic cells. However, it is only recently that the necessary sophisticated technology has been developed to begin testing this theory and its consequences. Vijg critically reviews the concept of genomic instability as a possible universal cause of aging in the context of a new, holistic understanding of genome functioning in complex organisms resulting from recent advances in functional genomics and systems biology. It provides an up-to-date synthesis of current research, as well as a look ahead to the design of strategies to retard or reverse the deleterious effects of aging. This is particularly important in a time when we are urgently trying to unravel the genetic component of aging-related diseases. Moreover, there is a growing public recognition of the imperative of understanding more about the underlying biology of aging, driven by continuing demographic change.
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The logic of aging
Genome structure and function
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Acad accelerated aging activity adverse effects age-related aging phenotypes aging process aging-related allele aneuploidy animals apoptosis Biol biology brain calorie restriction cancer cause of aging cellular Chapter chromatin chromosome complex cross-links defects deletions disease DNA damage DNA repair DNA sequence DSBs encoded enzyme eukaryotes evidence example factors fibroblasts function gene expression genetic genome alterations genome maintenance genome rearrangements genomic instability germ line histone human genome inactivation increased interactions involved lacz lesions levels lifespan liver longevity mammalian mammals mechanisms metabolism methylation mice mitochondrial molecular mouse models mtDNA mutation accumulation mutation frequency mutation loads Natl natural nematodes nuclear observed organisms oxidative pathways phenotypes polymerase population possible premature aging Proc proteins recombination replication reproduction response RNA polymerase role senescence signaling Sir2 somatic cells species spontaneous stem cells strand structure studies syndrome telomerase telomere tion tissues transcription tumor variation vivo Werner syndrome Whereas yeast