Gil Atzmon
A5047950133- Genetics, Aging, and Longevity in Model Organisms
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Birth, Development, and Health
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Adipose Tissue and Metabolism
- Telomeres, Telomerase, and Senescence
- Adipokines, Inflammation, and Metabolic Diseases
- Mitochondrial Function and Pathology
- Forensic and Genetic Research
- Genetics and Neurodevelopmental Disorders
- Growth Hormone and Insulin-like Growth Factors
- Diet and metabolism studies
- Regulation of Appetite and Obesity
- Genetic Mapping and Diversity in Plants and Animals
- Genetic diversity and population structure
- Pancreatic function and diabetes
- Inflammatory Bowel Disease
- CRISPR and Genetic Engineering
- Nutrition and Health in Aging
- Lipoproteins and Cardiovascular Health
- RNA regulation and disease
- Genomic variations and chromosomal abnormalities
- Cancer-related gene regulation
University of Haifa
2016-2025
Albert Einstein College of Medicine
2015-2024
The Bronx Defenders
2015-2021
Stanley Foundation
2019
Massachusetts General Hospital
2019
Broad Institute
2019
Oranim Academic College of Education
2019
Yeshiva University
2003-2015
Chinese Academy of Sciences
2013
Institute of Zoology
2013
Abstract Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences gene disruption: crucial for function an organism will be depleted such in natural populations, whereas non-essential tolerate their accumulation. However, predicted loss-of-function enriched annotation errors, and tend to found at extremely low frequencies, so analysis requires careful variant very large sample sizes 1 . Here we describe aggregation 125,748...
The incidence of hematologic cancers increases with age. These are associated recurrent somatic mutations in specific genes. We hypothesized that such would be detectable the blood some persons who not known to have disorders.
Structural variants (SVs) rearrange large segments of DNA
Rather than being a passive, haphazard process of wear and tear, lifespan can be modulated actively by components the insulin/insulin-like growth factor I (IGFI) pathway in laboratory animals. Complete or partial loss-of-function mutations genes encoding insulin/IGFI result extension life span yeasts, worms, flies, mice. This remarkable conservation throughout evolution suggests that altered signaling this may also influence human lifespan. On other hand, evolutionary tradeoffs predict...
Individuals with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes disease susceptibility.To identify specific genetic are associated or reliably define human phenotype.In case-control design, 213 Ashkenazi Jewish probands (mean [SD] age, 98.2 [5.3] years) offspring (n = 216; mean 68.3 [6.7] were recruited from 1998 to 2002, while an age-matched...
Age-dependent changes in insulin action and body fat distribution are risk factors for the development of type 2 diabetes. To examine whether accumulation visceral (VF) could play a direct role pathophysiology resistance diabetes, we monitored action, glucose tolerance, expression adipo-derived peptides after surgical removal VF aging (20-month-old) F344/Brown Norway (FBN) Zucker Diabetic Fatty (ZDF) rats. As expected, peripheral hepatic were markedly impaired FBN rats, extraction...
Type 2 diabetes (T2D) is a heterogeneous disease for which (1) disease-causing pathways are incompletely understood and (2) subclassification may improve patient management. Unlike other biomarkers, germline genetic markers do not change with progression or treatment. In this paper, we test whether approach informed by physiology can be used to deconstruct T2D heterogeneity. First, aimed categorize loci into groups representing likely mechanistic pathways. Second, asked the novel clusters of...
The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation this pathway influences humans, we genotyped 291 variants 30 genes encoding proteins the a cohort of elderly Caucasian women selected from Study Osteoporotic Fractures (SOF). included 293 long-lived cases (lifespan > or = 92 years (y), mean +/- standard deviation (SD) 95.3 2.2y) 603 average-lifespan controls < 79y, 75.7 2.6y)....
Crohn’s disease (CD)–associated variants in the LRRK2 gene for risk (N2081D) and protection (N551K) mediate shared effects CD Parkinson’s disease.
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations rare (with minor allele frequencies less than 0.5%) in 4 genes at exome-wide significance, including a series more 30 SLC30A8 alleles conveys protection against T2D, 12 gene sets, those...
Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization proportion mixture, or its date. We analyze genome-wide polymorphism data from about 40 groups to show almost all Southern Europeans inherited 1%-3% ancestry with an average mixture date around 55 generations ago, consistent North end Roman...
Summary Attenuated growth hormone and insulin‐like factor‐1 (GH/IGF‐1) signaling is associated with extended lifespan in several animal models. However, the effect of diminished GH/IGF‐1 activity on survival humans has not been confirmed. We tested hypothesis that IGF‐1 levels nonagenarians ( n = 184), measured at study enrollment, predict duration their incremental survival. In Kaplan–Meier analysis, females below median (≤ 96 ng mL −1 ) had significantly longer compared above median, P...
Abstract The acceleration of DNA sequencing in samples from patients and population studies has resulted extensive catalogues human genetic variation, but the interpretation rare variants remains problematic. A notable example this challenge is existence disruptive dosage-sensitive disease genes, even apparently healthy individuals. Here, by manual curation putative loss-of-function (pLoF) haploinsufficient genes Genome Aggregation Database (gnomAD) 1 , we show that one explanation for...
Abstract Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of gene inactivation complements knockout studies cells and organisms. Here we report three key findings regarding the assessment candidate drug targets using loss-of-function variants. First, even essential genes, which not tolerated, can be highly successful as inhibitory drugs. Second, most sufficiently rare genotype-based ascertainment homozygous or compound...
We previously identified a functional variant of KLOTHO , termed KL-VS, that is associated with human aging and early-onset occult coronary artery disease. Here, we determine whether the KL-VS allele influences cardiovascular disease risk factors, events, ultimately, mortality. A total 525 Ashkenazi Jews composed 216 probands (age ≥95 years) 309 unrelated individuals (ages 51 to 94) were genotyped for allele. In concordance our previous data in Czech ≥79; P <0.01), heterozygous advantage...
The distribution of serum TSH shifts progressively to higher concentrations with age.The aim the study was determine whether population shift in aging extends people exceptional longevity, namely centenarians, and assess relationship between free T(4) (FT4).We analyzed TSH, FT4, frequency curves thyroid disease-free Ashkenazi Jews longevity (centenarians; median age, 98 yr), younger controls (median 72 a individuals 68 yr) from U.S. National Health Nutrition Examination Survey 1998-2002...