How genetic analysis tests theories of animal aging

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Each animal species displays a specific life span, rate of aging and pattern of development of age-dependent diseases. The genetic bases of these related features are being studied experimentally in invertebrate and vertebrate model systems as well as in humans through medical records. Three types of mutants are being analyzed: (i) short-lived mutants that are prone to age-dependent diseases and might be models of accelerated aging; (ii) mutants that show overt molecular defects but that do not live shorter lives than controls, and can be used to test specific theories about the molecular causes of aging and age-dependent diseases; and (iii) long-lived mutants that might advance the understanding of the molecular physiology of slow-aging animals and aid the discovery of molecular targets that could be used to manipulate rates of aging to benefit human health. Here, I analyze some of what we know today and discuss what we should try to find out in the future to understand the aging phenomenon.

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Figure 1: Examples of life span studies in C. elegans and mice.
Figure 2: Schematic illustration of two important questions that can have independent answers.
Figure 3: The relationship between life span and age-dependent diseases.

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Acknowledgements

For discussions and insightful work, I thank the past and present members of my laboratory and my colleagues in the field. My laboratory is funded by McGill University, the National Science and Research Council of Canada (NSERC) and a research contract from Chronogen, Inc. I hold the Strathcona Chair of Zoology.

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S.H. is the founder of, a shareholder of, and a consultant for Chronogen, a biotechnology company interested in aging research.

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Hekimi, S. How genetic analysis tests theories of animal aging. Nat Genet 38, 985–991 (2006) doi:10.1038/ng1881

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