التفاصيل البيبلوغرافية
| العنوان: |
Depletion of loss-of-function germline mutations in centenarians reveals longevity genes |
| المؤلفون: |
Kejun Ying, José P. Castro, Anastasia V. Shindyapina, Alexander Tyshkovskiy, Mahdi Moqri, Ludger J. E. Goeminne, Sofiya Milman, Zhengdong D. Zhang, Nir Barzilai, Vadim N. Gladyshev |
| المصدر: |
Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024) |
| بيانات النشر: |
Nature Portfolio, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Science |
| مصطلحات موضوعية: |
Science |
| الوصف: |
Abstract While previous studies identified common genetic variants associated with longevity in centenarians, the role of the rare loss-of-function (LOF) mutation burden remains largely unexplored. Here, we investigated the burden of rare LOF mutations in Ashkenazi Jewish individuals from the Longevity Genes Project and LonGenity study cohorts using whole-exome sequencing data. We found that centenarians had a significantly lower burden (11-22%) of LOF mutations compared to controls. Similar effects were also observed in their offspring. Gene-level burden analysis identified 35 genes with depleted LOF mutations in centenarians, with 14 of these validated in the UK Biobank. Mendelian randomization and multi-omic analyses on these genes identified RGP1, PCNX2, and ANO9 as longevity genes with consistent causal effects on multiple aging-related traits and altered expression during aging. Our findings suggest that a protective genetic background, characterized by a reduced burden of damaging variants, contributes to exceptional longevity, likely acting in concert with specific protective variants to promote healthy aging. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-52967-2 |
| URL الوصول: |
https://doaj.org/article/5caa0089e32b4109a566c31b600051c0 |
| رقم الانضمام: |
edsdoj.5caa0089e32b4109a566c31b600051c0 |
| قاعدة البيانات: |
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