Martin George M, Bergman Aviv, Barzilai Nir
Department of Pathology, University of Washington, Seattle, Washington, United States of America.
PLoS Genet. 2007 Jul;3(7):e125. doi: 10.1371/journal.pgen.0030125.
We review three approaches to the genetic analysis of the biology and pathobiology of human aging. The first and so far the best-developed is the search for the biochemical genetic basis of varying susceptibilities to major geriatric disorders. These include a range of progeroid syndromes. Collectively, they tell us much about the genetics of health span. Given that the major risk factor for virtually all geriatric disorders is biological aging, they may also serve as markers for the study of intrinsic biological aging. The second approach seeks to identify allelic contributions to exceptionally long life spans. While linkage to a locus on Chromosome 4 has not been confirmed, association studies have revealed a number of significant polymorphisms that impact upon late-life diseases and life span. The third approach remains theoretical. It would require longitudinal studies of large numbers of middle-aged sib-pairs who are extremely discordant or concordant for their rates of decline in various physiological functions. We can conclude that there are great opportunities for research on the genetics of human aging, particularly given the huge fund of information on human biology and pathobiology, and the rapidly developing knowledge of the human genome.
我们综述了三种用于人类衰老生物学和病理生物学基因分析的方法。第一种也是迄今为止发展最为完善的方法是探寻对主要老年疾病易感性差异的生化遗传基础。这些疾病包括一系列早老性综合征。总体而言，它们让我们对健康寿命的遗传学有了很多了解。鉴于几乎所有老年疾病的主要风险因素都是生物衰老，它们也可能作为研究内在生物衰老的标志物。第二种方法旨在确定等位基因对超长寿命的贡献。虽然与4号染色体上一个位点的连锁尚未得到证实，但关联研究已经揭示了一些影响晚年疾病和寿命的重要多态性。第三种方法仍停留在理论层面。它需要对大量中年同胞对进行纵向研究，这些同胞对在各种生理功能衰退速度上差异极大或极为一致。我们可以得出结论，人类衰老遗传学的研究有很大机会，特别是考虑到关于人类生物学和病理生物学的大量信息，以及人类基因组知识的迅速发展。
