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Ageing

New mice for old questions

Nature volume 390, pages 18–19 (1997)Cite this article

In 1733, Alexander Pope1 wrote that man was “Created half to rise, and half to fall”. In other words, “First we ripen, then we rot”! Pope, it seems, was 250 years ahead of his time in anticipating the modern evolutionary theory of ageing2,3. This theory states that organisms in age-structured populations senesce because of the weakening of the force of natural selection as they grow older, which allows certain gene actions to reach deleterious levels of expression. In human populations, common examples include cataracts, Alzheimer's disease and other dementias, type 2 diabetes mellitus, osteoporosis (brittle bones), many types of cancer and several types of arteriosclerosis (hardening of the arteries). On page 45of this issue, Kuro-o and colleagues4 describe a single mutation in a mouse gene that, when homozygous, appears to accelerate several types of pathology associated with late-life disorders in humans (but not in mice).

Like hundreds of labs that introduce bits of genetic material into mice in the hopes of getting expression of such foreign genetic information, these investigators inadvertently made a random ‘hit’ that crippled one of the host's normal genes. Unlike many such labs, however, they decided to alter course and to investigate what seemed to be a model of accelerated ageing in man. We can all be happy that they made this decision, as the results are of considerable interest, although not fully explained and of questionable relevance to mechanisms of human senescence. A special merit of their study is that they re-introduced a normal version of the gene into the mutant animals and essentially normalized the phenotype, thus satisfying a sort of genetic equivalent of Koch's postulates.

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Figure 1: Comparison of human Klotho and archaeal lactase, proteins that contain β-glycosidase domains (labelled KL1 and KL2 in Klotho.).

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Authors and Affiliations

  1. the Department of Pathology, University of Washington, Seattle, 98195, Washington, USA

    George M. Martin

  2. the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    I. Saira Mian

Authors
  1. George M. Martin
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  2. I. Saira Mian
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Martin, G., Mian, I. New mice for old questions. Nature 390, 18–19 (1997). https://doi.org/10.1038/36210

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