We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population. Next, we used iGWAS to harness information from 14 meta-analyses of disease and trait GWAS to identify longevity loci in two studies of long-lived humans. In a standard GWAS analysis, only one locus in these studies is significant (APOE/TOMM40) when controlling the false discovery rate (FDR) at 10%. With iGWAS, we identify eight genetic loci to associate significantly with exceptional human longevity at FDR < 10%. We followed up the eight lead SNPs in independent cohorts, and found replication evidence of four loci and suggestive evidence for one more with exceptional longevity. The loci that replicated (FDR < 5%) included APOE/TOMM40 (associated with Alzheimer's disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease). Our results implicate new loci in longevity and reveal a genetic overlap between longevity and age-related diseases and traits, including coronary artery disease and Alzheimer's disease. iGWAS provides a new analytical strategy for uncovering SNPs that influence extreme longevity, and can be applied more broadly to boost power in other studies of complex phenotypes.
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http://dx.doi.org/10.1371/journal.pgen.1005728 | DOI Listing |
Materials (Basel)
January 2025
Mechanical Engineering Department, Universidad Carlos III de Madrid, 28911 Leganés, Spain.
The degradation of rubber materials under environmental and mechanical stress presents a significant challenge, particularly due to UV (ultraviolet light) exposure, which severely impacts the material's physical properties. This study aims to enhance the UV stability and longevity of rubber by evaluating the performance of modified polyurethane and silicone coatings as protective stabilizers. Natural rubber-styrene-butadiene rubber (NR-SBR), known for its exceptional mechanical properties, was selected as the base material.
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January 2025
Central laboratory of Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China. Electronic address:
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January 2025
Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, Santa Cruz, CA 95060, USA.
The rate at which mutations arise is a fundamental parameter of biology. Despite progress in measuring germline mutation rates across diverse taxa, such estimates are missing for much of Earth's biodiversity. Here, we present the first estimate of a germline mutation rate from the phylum Mollusca.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Artificial Intelligence Research Center, Institute of Information Technologies, Mathematics and Mechanics, Lobachevsky State University, 603022 Nizhny Novgorod, Russia.
Yakutia is one of the coldest permanently inhabited regions in the world, characterized by a subarctic climate with average January temperatures near -40 °C and the minimum below -60 °C. Recently, we demonstrated accelerated epigenetic aging of the Yakutian population in comparison to their Central Russian counterparts, residing in a considerably milder climate. In this paper, we analyzed these cohorts from the inflammaging perspective and addressed two hypotheses: a mismatch in the immunological profiles and accelerated inflammatory aging in Yakuts.
View Article and Find Full Text PDFBiology (Basel)
December 2024
Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, 90134 Palermo, Italy.
Studying models of healthy aging and exceptional longevity is crucial to understanding a possible longevity signature, as most show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyzes the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, aiming to understand the immune-inflammatory (IMFLAM) role in achieving longevity.
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