Chromosomal instability and aging : basic science and by Fuki Hisama, Sherman M. Weissman, George M. Martin

By Fuki Hisama, Sherman M. Weissman, George M. Martin

This article examines the connection among DNA harm and service, mobile senescence, genomic instability, and getting older. The authors supply in-depth discussions of varied varieties of DNA harm, the DNA fix community, and mobile responses to genetic harm to evaluate their impression at the modulation of getting older tactics and age-related illnesses, together with melanoma improvement. Chromosomal Instability and getting older describes cloning genes for human chromosomal instability issues, the causal components and outcomes of chromosomal harm, the telomere speculation of getting older, and age-dependant mitochondrial genetic instability. It contains greater than 2200 references to facilitate extra examine, making it an informative and well timed advisor.

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Elegans in Chapter 20. An emerging theme from the study of dozens of distinct mutations is the relationship of longevity to increased stress resistance and conversely shortened life span with decreased stress resistance. Tower’s Chapter 21 on aging, somatic maintenance, and genomic stability in D. melanogaster describes the research using a variety of methods, including genetic selection of populations, single-gene mutations, and overexpression of transgenes to determine effects on life span. He argues that with the exception of transcription coupled repair, most of the major pathways of DNA repair are represented in Drosophila, and that the potential role of the relevant genes in regulating aging and genomic instability is an exciting area of exploration.

Genetic instability and Darwinian selection in tumours. Trends Cell Biol 9: 57–60, 1999. MJ Arends, AH Wyllie. Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol 32:223–254, 1991. JC Reed. Mechanisms of apoptosis in avoidance of cancer. Curr Opin Oncol 11:68–75, 1999. R Sager. Senescence as a mode of tumor suppression. Environ Health Persp 93:59–62, 1991. D Hanahan, RA Weinberg. The hallmarks of cancer. Cell 100:57–70, 2000. RR Reddel. The role of senescence and immortalization in carcinogenesis.

Moreover, much of this growth-promoting activity could be attributed to the secretory phenotype of the senescent fibroblasts. Thus, despite protecting from cancer in young adults, cellular senescence may facilitate the development of cancer in aged organisms (see Fig. 1). A number of hereditary syndromes have now been identified that cause genomic instability, susceptibility to cancer, and, in many cases, the premature development of a subset of aging phenotypes in mammals. These include the Werner and Bloom syndromes, which are caused by mutations or disruptions in the genes encoding the WRN and BLM DNA helicases (81,179), respectively.

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