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. 2021 Apr 28:2021:5530293.
doi: 10.1155/2021/5530293. eCollection 2021.

Mitochondrial Dysfunction Contributes to Aging-Related Atrial Fibrillation

Chuanbin Liu  1   2 , Jing Bai  1 , Qing Dan  3 , Xue Yang  2   4 , Kun Lin  3 , Zihao Fu  1 , Xu Lu  1 , Xiaoye Xie  1   2 , Jianwei Liu  2   4 , Li Fan  2   4 , Yang Li  3
Affiliations

Mitochondrial Dysfunction Contributes to Aging-Related Atrial Fibrillation

Chuanbin Liu et al. Oxid Med Cell Longev. .

Abstract

The incidence of atrial fibrillation (AF) increases with age, and telomere length gradually shortens with age. However, whether telomere length is related to AF is still inconclusive, and the exact mechanism by which aging causes the increased incidence of AF is still unclear. We hypothesize that telomere length is correlated with aging-related AF and that mitochondrial dysfunction plays a role in this. This research recruited 96 elderly male patients with AF who were admitted to the Second Medical Center of Chinese PLA General Hospital from April to October 2018. After matching by age and gender, 96 non-AF elderly male patients who were admitted to the hospital for physical examination during the same period were selected as controls. Anthropometric, clinical, and laboratory analyses were performed on all subjects. The mitochondrial membrane potential (MMP) of peripheral blood leukocytes was detected as the indicator of mitochondrial function. Compared with the control group, the leukocyte telomere length (LTL) was significantly shorter (P < 0.001), and the level of PGC-1α in serum was significantly lower in AF patients. Additionally, in subjects without any other diseases, the AF patients had lower MMP when compared with the control. Multivariate logistic regression confirmed that LTL (OR 0.365; 95% CI 0.235-0.568; P < 0.001) and serum PGC-1α (OR 0.993; 95% CI 0.988-0.997; P = 0.002) were inversely associated with the presence of AF. In addition, ROC analysis indicated the potential diagnostic value of LTL and serum PGC-1α with AUC values of 0.734 and 0.633, respectively. This research concludes that LTL and serum PGC-1α are inversely correlated with the occurrence of aging-related AF and that mitochondrial dysfunction plays a role in this.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
Study frame diagram. AF: atrial fibrillation.
Figure 2
Figure 2
LTL in AF patients and the controls. (a) AF patients showed significantly shorter LTL compared with controls; (b) quartile distribution of LTL; (c) LTL in elderly males was significantly negatively correlated with age; (d) LTL was significantly shorter in AF patients in the elderly age group and senile age group; (e) there were no significant differences of LTL among the paroxysmal AF, persistent AF, and permanent AF groups. LTL: leukocyte telomere length; AF: atrial fibrillation; Q: quartile.
Figure 3
Figure 3
Telomere-associated molecules in AF patients. (a) p53 mRNA in AF patients was higher than controls and without statistical differences; (b, c) no significant differences of p53 mRNA among different types of AF and different age groups; (d) the expression of PGC-1α mRNA in leukocytes was significantly reduced in AF patients; (e) no significant differences of PGC-1α mRNA among different types of AF; (f) the expression of PGC-1α mRNA was significantly lower in AF patients in the long-living age group; (g) the serum PGC-1α concentration was significantly reduced in AF patients; (h) no significant differences of serum PGC-1α concentration among different types of AF; (i) the serum PGC-1α concentration was significantly reduced in AF patients in the elderly age group and senile age group. AF: atrial fibrillation.
Figure 4
Figure 4
LTL, PGC-1α expression, and MMP in subgroup of patients without other diseases. (a) AF patients showed significantly shorter LTL compared with controls; (b) the expression of PGC-1α mRNA in leukocytes was significantly reduced in AF patients; (c) the serum PGC-1α concentration was significantly reduced in AF patients; (d) representative pictures of MMP detected by flow cytometry; (e) the MMP of AF patients was significantly decreased when compared with controls. AF: atrial fibrillation; MMP: mitochondrial membrane potential.
Figure 5
Figure 5
Multiple logistic regression analysis for the presence of AF. BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol; UA: uric acid; CRP: C-reactive protein; LAD: left atrial diameter; LTL: leukocyte telomere length.
Figure 6
Figure 6
ROC curves of LTL, PGC-1α, and CRP to predict AF. ROC analysis was performed to determine the sensitivity and specificity of the value. ROC: receiver operator characteristic; AUC: area under the curve; CI: confidence interval; LTL: leukocyte telomere length; CRP: C-reactive protein.
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