Age-related mitochondrial DNA deletion in human heart: its relationship with cardiovascular diseases
Tomio Arai1, Ken-ichi Nakahara, Hiroko Matsuoka
1Departments of Pathology, Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan. arai@tmig.or.jp
Insights
Mitochondrial DNA (mtDNA) deletions increase with age in heart tissue, particularly in individuals over 90. While common, these age-related mtDNA deletions show limited links to cardiovascular diseases, except for right ventricular hypertrophy.
Area of Science:
- Cardiovascular Science
- Aging Research
- Molecular Biology
Background:
- Mitochondrial DNA (mtDNA) damage accumulates in heart tissue with aging.
- Cardiovascular diseases are more prevalent in the elderly, yet mtDNA deletions in aged hearts are understudied.
Purpose of the Study:
- To investigate the relationship between aging, mitochondrial DNA (mtDNA) deletions, and cardiovascular diseases.
- To determine the prevalence and characteristics of mtDNA deletions in the myocardial tissue of aged individuals.
Main Methods:
- Analysis of 163 autopsy cases aged 60 and older.
- Utilized highly sensitive PCR for a common 4977-bp deletion and long-PCR for multiple deletions in cardiac mtDNA.
Main Results:
- The common 4977-bp deletion was found in 95.7% of cases, unrelated to age or cardiovascular disease.
- Multiple mtDNA deletions were detected in 20.2% of cases, with higher prevalence in individuals in their nineties (46.2%) compared to younger groups (15.3%).
- Female predominance was observed in the mtDNA deletion group; deletions were linked to right ventricular hypertrophy but not other cardiovascular conditions.
Conclusions:
- A strong correlation exists between aging and mtDNA deletion, with the ratio of deleted mtDNA increasing with age.
- Age-related mtDNA deletions appear to have minimal impact on cardiovascular diseases, with the exception of right ventricular hypertrophy.
Background And Aims:
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.
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