Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals
Current research on the angiotensin-converting-enzyme (<i>ACE</i>) gene has yielded controversial results on whether different <i>ACE</i> polymorphisms are linked with human longevity. <i>ACE</i> polymorphisms are a risk factor for Alzheimer’s disease and age-onse...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3411 |
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| author | Lingxuan Li Shin Murakami |
| author_facet | Lingxuan Li Shin Murakami |
| author_sort | Lingxuan Li |
| collection | DOAJ |
| description | Current research on the angiotensin-converting-enzyme (<i>ACE</i>) gene has yielded controversial results on whether different <i>ACE</i> polymorphisms are linked with human longevity. <i>ACE</i> polymorphisms are a risk factor for Alzheimer’s disease and age-onset diseases that may contribute to the mortality of older people. Our goal is to consolidate existing studies, using artificial intelligence-assisted software to come to a more precise understanding of the role of the <i>ACE</i> gene in human longevity. The I (insertion) and D (deletion) polymorphisms in the intron are correlated with the levels of circulating ACE; homozygous D (DD) is high, and homozygous I (II) is low. Here, we performed a detailed meta-analysis of the I and D polymorphisms using centenarians (100+ years old), long-lived subjects (85+ years old), and control groups. <i>ACE</i> genotype distribution was analyzed across a total of 2054 centenarians and 12,074 controls, as well as 1367 long-lived subjects between the ages of 85–99, using the inverse variance and random effects methods. The <i>ACE</i> DD genotype was found to be favored in centenarians (OR: 1.41 (95% CI: 1.19–1.67), <i>p</i> < 0.0001) with a heterogeneity of 32%, and the II genotype slightly favored the control groups (OR: 0.81 (95% CI: 0.66–0.98), <i>p</i> = 0.03) with a heterogeneity of 28%, corroborating results from previous meta-analyses. Novel to our meta-analysis, the ID genotype was found to be favored in control groups (OR: 0.86 (95% CI: 0.76–0.97), <i>p</i> = 0.01) with a heterogeneity of 0%. The long-lived group showed a similar positive association between the DD genotype and longevity (OR: 1.34 (95% CI: 1.21–1.48), <i>p</i> < 0.0001) and a negative association between the II genotype and longevity (OR: 0.79 (95% CI: 0.70–0.88), <i>p</i> < 0.0001). The long-lived ID genotype did not show significant findings (OR: 0.93 (95% CI: 0.84–1.02), <i>p</i> = 0.79). In conclusion, the results suggest a significant positive association of the DD genotype with human longevity. However, despite the previous study, the results do not confirm a positive association of the ID genotype with human longevity. We suggest a few important paradoxical implications: (1) inhibition of ACE can increase longevity in model systems from nematodes to mammals, seemingly opposite to the finding in humans; (2) exceptional longevity associated with homozygous DD is also associated with age-related diseases with higher mortality risks in homozygous DD. We discuss <i>ACE</i>, longevity, and age-related diseases. |
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| spelling | doaj.art-2f38476def3b423fae5790f606f9ee4a2023-11-16T20:59:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244341110.3390/ijms24043411Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived IndividualsLingxuan Li0Shin Murakami1Department of Basic Sciences, College of Osteopathic Medicine, Touro University California, Vallejo, CA 94592, USADepartment of Basic Sciences, College of Osteopathic Medicine, Touro University California, Vallejo, CA 94592, USACurrent research on the angiotensin-converting-enzyme (<i>ACE</i>) gene has yielded controversial results on whether different <i>ACE</i> polymorphisms are linked with human longevity. <i>ACE</i> polymorphisms are a risk factor for Alzheimer’s disease and age-onset diseases that may contribute to the mortality of older people. Our goal is to consolidate existing studies, using artificial intelligence-assisted software to come to a more precise understanding of the role of the <i>ACE</i> gene in human longevity. The I (insertion) and D (deletion) polymorphisms in the intron are correlated with the levels of circulating ACE; homozygous D (DD) is high, and homozygous I (II) is low. Here, we performed a detailed meta-analysis of the I and D polymorphisms using centenarians (100+ years old), long-lived subjects (85+ years old), and control groups. <i>ACE</i> genotype distribution was analyzed across a total of 2054 centenarians and 12,074 controls, as well as 1367 long-lived subjects between the ages of 85–99, using the inverse variance and random effects methods. The <i>ACE</i> DD genotype was found to be favored in centenarians (OR: 1.41 (95% CI: 1.19–1.67), <i>p</i> < 0.0001) with a heterogeneity of 32%, and the II genotype slightly favored the control groups (OR: 0.81 (95% CI: 0.66–0.98), <i>p</i> = 0.03) with a heterogeneity of 28%, corroborating results from previous meta-analyses. Novel to our meta-analysis, the ID genotype was found to be favored in control groups (OR: 0.86 (95% CI: 0.76–0.97), <i>p</i> = 0.01) with a heterogeneity of 0%. The long-lived group showed a similar positive association between the DD genotype and longevity (OR: 1.34 (95% CI: 1.21–1.48), <i>p</i> < 0.0001) and a negative association between the II genotype and longevity (OR: 0.79 (95% CI: 0.70–0.88), <i>p</i> < 0.0001). The long-lived ID genotype did not show significant findings (OR: 0.93 (95% CI: 0.84–1.02), <i>p</i> = 0.79). In conclusion, the results suggest a significant positive association of the DD genotype with human longevity. However, despite the previous study, the results do not confirm a positive association of the ID genotype with human longevity. We suggest a few important paradoxical implications: (1) inhibition of ACE can increase longevity in model systems from nematodes to mammals, seemingly opposite to the finding in humans; (2) exceptional longevity associated with homozygous DD is also associated with age-related diseases with higher mortality risks in homozygous DD. We discuss <i>ACE</i>, longevity, and age-related diseases.https://www.mdpi.com/1422-0067/24/4/3411age-related comorbidityangiotensin-converting enzymecentenariansmeta-analysislongevitylife extension |
| spellingShingle | Lingxuan Li Shin Murakami Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals International Journal of Molecular Sciences age-related comorbidity angiotensin-converting enzyme centenarians meta-analysis longevity life extension |
| title | Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals |
| title_full | Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals |
| title_fullStr | Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals |
| title_full_unstemmed | Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals |
| title_short | Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals |
| title_sort | artificial intelligence assisted meta analysis of the frequency of ace i d polymorphisms in centenarians and other long lived individuals |
| topic | age-related comorbidity angiotensin-converting enzyme centenarians meta-analysis longevity life extension |
| url | https://www.mdpi.com/1422-0067/24/4/3411 |
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