Fahn H J, Wang L S, Hsieh R H, Chang S C, Kao S H, Huang M H, Wei Y H
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taiwan, Republic of China.
Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1141-5. doi: 10.1164/ajrccm.154.4.8887618.
The accumulation of mitochondrial DNA (mtDNA) mutations has been suggested to be an important contributor to human aging and degenerative diseases. The lung is exposed to ambient air and makes direct contact with the external environment. Numerous potentially noxious agents may damage lung tissues directly or indirectly through free-radical-mediated reactions. In previous studies, we demonstrated an age-dependent increase of mtDNA mutations in various human tissues. We hypothesize that the accumulation of the 4,977 bp (base pairs) deleted mtDNA in human lung tissues is also age-dependent. Using the polymerase chain reaction technique, we determined the incidence of the 4,977 bp-deleted mtDNA in 127 human lung specimens from 34-wk gestation to 79 yr of age. The results showed that 77 lung biopsies (60.6%) contained the 4,977 bp-deleted mtDNA, which started to appear in lung tissues after the fourth decade of life. The incidence apparently increased from 14.3% (one of seven) of the subjects in the 30- to 39-yr age group to 77.8% (two of 27) of the subjects in the 70- to 79-yr age group (p < 0.0001). The mean (+/- SEM) proportion of the 4,977 bp-deleted mtDNA in lung tissues significantly increased from 0.007 +/- 0.007% of the subjects in the 30- to 39-yr age group to 0.833 +/- 0.330% of those in the 70- to 79-yr age group (p < 0.005). Other factors such as sex, pulmonary function indices, and smoking status did not have statistically significant impact on the amount of the deleted mtDNA. These findings suggest that the accumulation of the 4,977 bp-deleted mtDNA is associated with aging human lung.
线粒体DNA（mtDNA）突变的积累被认为是人类衰老和退行性疾病的一个重要因素。肺暴露于环境空气中，并与外部环境直接接触。许多潜在的有害物质可能通过自由基介导的反应直接或间接损害肺组织。在先前的研究中，我们证明了各种人类组织中mtDNA突变随年龄增长而增加。我们假设人类肺组织中4977碱基对（bp）缺失的mtDNA的积累也与年龄有关。使用聚合酶链反应技术，我们测定了127份从妊娠34周龄到79岁的人类肺标本中4977 bp缺失的mtDNA的发生率。结果显示，77份肺活检标本（60.6%）含有4977 bp缺失的mtDNA，其在生命的第四个十年后开始出现在肺组织中。发生率明显从30至39岁年龄组受试者的14.3%（7人中有1人）增加到70至79岁年龄组受试者的77.8%（27人中有2人）（p<0.0001）。肺组织中4977 bp缺失的mtDNA的平均（±标准误）比例从30至39岁年龄组受试者的0.007±0.007%显著增加到70至79岁年龄组受试者的0.833±0.330%（p<0.005）。其他因素，如性别、肺功能指标和吸烟状况，对缺失的mtDNA数量没有统计学上的显著影响。这些发现表明，4977 bp缺失的mtDNA的积累与人类肺的衰老有关。
