Am. J. Respir. Crit. Care Med., Vol 154, No. 4, Oct 1996, 1141-1145.
Age-related 4,977 bp deletion in human lung mitochondrial DNA
HJ Fahn, LS Wang, RH Hsieh, SC Chang, SH Kao, MH Huang and YH Wei
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taiwan, Republic of China.
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.
