Martin George M
Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Cell. 2005 Feb 25;120(4):523-32. doi: 10.1016/j.cell.2005.01.031.
Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or "normative" aging. These can be divided into two classes--those that have their impacts upon multiple organs and tissues (segmental progeroid syndromes) and those that have their major impacts upon a single organ or tissue (unimodal progeroid syndromes). The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases. Research on the Werner syndrome and a surprising number of other progeroid syndromes support the importance of the maintenance of genomic stability as a partial antidote to aging. The prototypic examples of the latter are Alzheimer type dementias. The three gene products that cause rare autosomal-dominant early-onset varieties of these disorders all participate in the modulation of the beta amyloid precursor protein. They thus support the importance of the maintenance of proper protein processing and folding as a partial antidote to aging.
单基因突变可导致人类早衰综合征——即模仿正常或“标准”衰老的表型。这些早衰综合征可分为两类——一类对多个器官和组织产生影响（节段性早衰综合征），另一类主要对单个器官或组织产生影响（单峰性早衰综合征）。前者的典型例子是沃纳综合征，这是一种由DNA解旋酶RecQ家族突变引起的疾病。对沃纳综合征以及数量惊人的其他早衰综合征的研究支持了维持基因组稳定性作为对抗衰老的部分解药的重要性。后者的典型例子是阿尔茨海默型痴呆症。导致这些疾病罕见的常染色体显性早发型变体的三种基因产物都参与了β淀粉样前体蛋白的调节。因此，它们支持了维持适当的蛋白质加工和折叠作为对抗衰老的部分解药的重要性。
