Rare genetic coding variants associated with human longevity and protection against age-related diseases.

Autor: Lin JR; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Sin-Chan P; Regeneron Pharmaceuticals Inc., New York, NY, USA., Napolioni V; School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy., Torres GG; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany., Mitra J; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Zhang Q; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Jabalameli MR; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Wang Z; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Nguyen N; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Gao T; Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA., Laudes M; Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Internal Medicine I, Kiel University, Kiel, Germany., Görg S; Institute of Transfusion Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany., Franke A; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany., Nebel A; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany., Greicius MD; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA., Atzmon G; Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.; Department of Biology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel., Ye K; Department of Epidemiology & Population Health, Albert Einstein College of Medicine, New York, NY, USA., Gorbunova V; Department of Biology, University of Rochester, Rochester, NY, USA., Ladiges WC; Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA., Shuldiner AR; Regeneron Pharmaceuticals Inc., New York, NY, USA., Niedernhofer LJ; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA., Robbins PD; Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA., Milman S; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA.; Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA., Suh Y; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA.; Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA., Vijg J; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Barzilai N; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA.; Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA., Zhang ZD; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA. zhengdong.zhang@einsteinmed.org.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2021 Sep; Vol. 1 (9), pp. 783-794. Date of Electronic Publication: 2021 Sep 13.
DOI: 10.1038/s43587-021-00108-5
Abstrakt: Extreme longevity in humans has a strong genetic component, but whether this involves genetic variation in the same longevity pathways as found in model organisms is unclear. Using whole-exome sequences of a large cohort of Ashkenazi Jewish centenarians to examine enrichment for rare coding variants, we found most longevity-associated rare coding variants converge upon conserved insulin/insulin-like growth factor 1 signaling and AMP-activating protein kinase signaling pathways. Centenarians have a number of pathogenic rare coding variants similar to control individuals, suggesting that rare variants detected in the conserved longevity pathways are protective against age-related pathology. Indeed, we detected a pro-longevity effect of rare coding variants in the Wnt signaling pathway on individuals harboring the known common risk allele APOE4. The genetic component of extreme human longevity constitutes, at least in part, rare coding variants in pathways that protect against aging, including those that control longevity in model organisms.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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