Aging of the Genome: The Dual Role of DNA in Life and Death by Jan Vijg

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By Jan Vijg

Getting older has lengthy in view that been ascribed to the sluggish accumulation of DNA mutations within the genome of somatic cells. notwithstanding, it is just lately that the required refined know-how has been constructed to start trying out this concept and its outcomes. Vijg seriously studies the concept that of genomic instability as a potential common reason behind getting older within the context of a brand new, holistic figuring out of genome functioning in complicated organisms caused by contemporary advances in useful genomics and platforms biology. It offers an up to date synthesis of present learn, in addition to a glance forward to the layout of ideas to retard or opposite the deleterious results of getting older. this can be rather vital in a time once we are urgently attempting to get to the bottom of the genetic portion of aging-related illnesses. in addition, there's a becoming public attractiveness of the crucial of realizing extra in regards to the underlying biology of getting older, pushed by way of carrying on with demographic swap.

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This convergence will happen in an approach known as systems biology (Fig. 4). Systems biology studies the interrelationships of all the elements in a Systems biology Predictive modeling Phenome Computational analysis Metabolome Interactome Functional genomics High-throughput measurements Proteome Transcriptome Perturbation Genome Fig. 4 The holistic science of systems biology attempts to define biological realities on the basis of global responses of cells, organs, or entire organisms to environmental or genetic perturbations.

A high rate of germ-line mutation can lead to population extinction, which may have been the driving force behind the evolution of sex, mate choice, and diploid life cycles, all ways to limit the adverse effects of mutations. Since the adverse effects of mutations in somatic cells would only become manifest at late age, selection to improve the accuracy of DNA metabolism far beyond the age of first reproduction is absent. THE LOGIC OF AGING 39 Antagonistic pleiotropy can also act directly on reproductive success (sexual selection) rather than on the ability to deal with environmental factors (survival selection).

Of note, while this increase in mortality has been observed in all species that undergo aging, at very old age it no longer seems to hold. This has been most convincingly demonstrated for invertebrate species, large numbers of which can be studied relatively easily. Large-scale studies of the lifespans of tens of thousands of medflies, fruit flies, or nematode worms have shown a deceleration of mortality at old age, which may in fact also be true for humans56. The slopes of the Gompertz plots (Fig.

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