Familial longevity study reveals a significant association of mitochondrial DNA copy number between centenarians and their offspring.
Reduced mitochondrial function is an important cause of aging and age-related diseases. We previously revealed a relatively higher level of mitochondrial DNA (mtDNA) content in centenarians. However, it is still unknown whether such an mtDNA content pattern of centenarians could be passed on to their offspring and how it was regulated. To address these issues, we recruited 60 longevity families consisting of 206 family members (cohort 1) and explored their mtDNA copy number. The results showed that the first generation of the offspring (F1 offspring) had a higher level of mtDNA copy number than their spouses (p < 0.05) independent of a gender effect. In addition, we found a positive association of mtDNA copy number in centenarians with that in F1 offspring (r = 0.54, p = 0.0008) but not with that in F1 spouses. These results were replicated in another independent cohort consisting of 153 subjects (cohort 2). RNA sequencing analysis suggests that the single-stranded DNA-binding protein 4 was significantly associated with mtDNA copy number and was highly expressed in centenarians as well as F1 offspring versus the F1 spouses, thus likely regulates the mtDNA copy number in the long-lived family members. In conclusion, our results suggest that the pattern of high mtDNA copy number is likely inheritable, which may act as a favorable factor to familial longevity through assuring adequate energy supply.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China.
Yong-Han
YH
He
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China.
Xiao-Qiong
XQ
Chen
Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, China.
Dong-Jing
DJ
Yan
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
Fu-Hui
FH
Xiao
Department of Biology, Hainan Medical College, Haikou, China.
Rong
R
Lin
Department of Neurology, The Affiliated Hospital of Hainan Medical College, Haikou, China.
Xiao-Ping
XP
Liao
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
Yao-Wen
YW
Liu
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China.
Shao-Yan
SY
Pu
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
Qin
Q
Yu
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, China.
Hong-Peng
HP
Sun
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
Jian-Jun
JJ
Jiang
Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, China. Electronic address: caiww591020@163.com.
Wang-Wei
WW
Cai
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China. Electronic address: kongqp@mail.kiz.ac.cn.
Qing-Peng
QP
Kong
D000369:Aged, 80 and over; D056915:DNA Copy Number Variations / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins
Copy number; Familial longevity; Mitochondrial DNA; Single-stranded DNA-binding protein 4