Age-related mitochondrial DNA deletion in human heart: its relationship with cardiovascular diseases.
OBJECTIVE
Accumulation of damage to mitochondrial DNA (mtDNA) occurs in myocardial tissue with advancing age. However, despite higher incidence of cardiac diseases in the elderly, little attempt has been made to detect deletions of mtDNA in the myocardial tissue of aged individuals. The aim of the present study was to clarify the relationship between aging, mtDNA deletion and cardiovascular (CV) diseases.


METHODS
We examined 163 autopsy cases, aged 60 years or older, using two different kinds of polymerase chain reaction (PCR): highly sensitive PCR to detect a common 4977-bp deletion and long-PCR for multiple deletions, which could be detected in case that deleted mtDNA accounted for more than several percents in total mtDNA.


RESULTS
The common 4977-bp deletion was detected in 156 cases (95.7%), showing no significant difference among these age groups and no relation to CV diseases. By long-PCR, multiple deletions in cardiac mtDNA were found in 33 (20.2%) of 163 cases. The proportion of the mtDNA deletion in the nineties (46.2%) was significantly higher than those in the younger (15.3%, p < 0.05). Female predominance was significantly found in the group with the mtDNA deletion (p < 0.05). Multiple deletions of mtDNA were not significantly related to ischemic change, valvular diseases, left ventricular hypertrophy, congestive heart failure, coronary sclerosis, or heart weight except for right ventricular hypertrophy.


CONCLUSIONS
These findings suggest that there is a close relationship between aging and deletion of mtDNA, and that the ratio of deleted mtDNA to total mtDNA increases with advancing age. Age-related deletion of mtDNA may have little influence on CV diseases except for right ventricular hypertrophy.
Arai
Tomio
T
Departments of Pathology, Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan. arai@tmig.or.jp
Nakahara
Ken-ichi
K
Matsuoka
Hiroko
H
Sawabe
Motoji
M
Chida
Koji
K
Matsushita
Satoru
S
Takubo
Kaiyo
K
Honma
Naoko
N
Nakamura
Ken-ichi
K
Izumiyama
Naotaka
N
Esaki
Yokiyoshi
Y
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006321:Heart / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods
D004272:DNA, Mitochondrial