A5085542503- Genetic Associations and Epidemiology
- Genetics, Aging, and Longevity in Model Organisms
- Health disparities and outcomes
- Birth, Development, and Health
- Health, Environment, Cognitive Aging
- Insurance, Mortality, Demography, Risk Management
- Global Health Care Issues
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Dementia and Cognitive Impairment Research
- Nutrition, Genetics, and Disease
- Frailty in Older Adults
- Health Systems, Economic Evaluations, Quality of Life
- Genetic and phenotypic traits in livestock
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Nutrition and Health in Aging
- Folate and B Vitamins Research
- Genetic Mapping and Diversity in Plants and Animals
- Immune responses and vaccinations
- Healthcare Policy and Management
- Chronic Disease Management Strategies
- Statistical Methods and Bayesian Inference
- Genetics and Neurodevelopmental Disorders
Social Science Research Council
2016-2025
Duke University
2016-2025
Institute of Biophysics
2017
Chinese Academy of Sciences
2017
Center for Child and Family Health
2009-2013
China Population and Development Research Center
2012
Duke Medical Center
2012
Urals Research Center for Radiation Medicine
2008
Max Planck Institute for Demographic Research
2000-2001
Abstract Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes centenarians, whose genomes may harbor genetic variants health and longevity. Here we report a association study (GWAS) Han Chinese size 2.7 times the largest previously published GWAS on centenarians. We 11 independent replicated in Southern-Northern regions China, including novel (rs2069837- IL6 ; rs2440012- ANKRD20A9P ) significance rest...
Abstract Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts progression the context intact immune system is unknown. Here we report that while inhibiting immunocompromised mice, reduces T cell abundance, exacerbates tumour impairs response immunotherapy immunocompetent male female mice. Mechanistically, microbial production hydrogen...
<h3>Importance</h3> Leukocyte telomere length (LTL) is a trait associated with risk of cardiovascular disease and cancer, the 2 major categories that largely define longevity in United States. However, it remains unclear whether LTL human life span. <h3>Objective</h3> To examine span contemporary humans. <h3>Design, Setting, Participants</h3> This cohort study included 3259 adults European ancestry from Cardiovascular Health Study (CHS), Framingham Heart (FHS), Women’s Initiative (WHI). was...
Diverse pathogens (viral, bacterial, fungal) have been associated with Alzheimer's disease (AD) and related traits in various studies. This suggests that compromised immunity, rather than specific microbes, may play a role AD by increasing an individual's vulnerability to infections, which could contribute neurodegeneration. If true, then vaccines heterologous effects on extending beyond protection against the targeted disease, hold potential for prevention.
Objectives To use the Medicare Files of Service Use ( MFSU ) to evaluate patterns in incidence aging‐related diseases U.S. elderly population. Design Age‐specific rates 19 were evaluated using National Long Term Care Survey NLTCS and Surveillance, Epidemiology, End Results SEER Registry data, both linked NLTCS‐M SEER‐M , respectively), an algorithm developed for individual date at onset evaluation. Setting A random sample from entire population (Medicare beneficiaries) was used data covers...
<h3>Importance</h3> Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized health care. <h3>Objective</h3> To explore sex longevity. <h3>Design, Setting, and Participants</h3> This population-based case-control study used sex-specific genome-wide association polygenic risk score (PRS) analyses to examine Five hundred sixty-four male 1614 female participants older than 100 years were compared a control...
Alzheimer's disease (AD) is the most common cause of dementia in elderly and sixth leading death United States. AD mainly considered a complex disorder with polygenic inheritance. Despite discovering many susceptibility loci, major proportion genetic variance remains to be explained.We investigated architecture four publicly available independent datasets through genome-wide association, transcriptome-wide gene-based pathway-based analyses. To explore differences basis between males females,...
Decline in biological resilience (ability to recover) is a key manifestation of aging that contributes increase vulnerability death with age eventually limiting longevity even people without major chronic diseases. Understanding the mechanisms this decline essential for developing efficient anti-aging and pro-longevity interventions. In paper we discuss: a) age, components contribute decline, including depletion body reserves, imperfect repair mechanisms, slowdown physiological processes...
Functional decline associated with dementia, including in Alzheimer's disease (AD), is not uniform across individuals, and respective heterogeneity yet fully explained. Such may part be related to genetic variability among individuals. In this study, we investigated whether the SNP rs6859 nectin cell adhesion molecule 2 (NECTIN2) gene (a major risk factor for AD) influences trajectories of cognitive older participants from Disease Neuroimaging Initiative (ADNI).
The results of genome-wide association studies complex traits, such as life span or age at onset chronic disease, suggest that traits are typically affected by a large number small-effect alleles. Individually alleles have little predictive values, therefore they were usually excluded from further analyses. our study strongly the with small individual effects on longevity may jointly influence so resulting can be both substantial and significant. We show this joint described relatively...
Recently suggested novel implementation of the statistical distance measure (DM) for evaluating "physiological dysregulation" (PD) in aging individuals (based on measuring deviations multiple biomarkers from baseline or normal physiological states) allows reducing high-dimensional biomarker space into a single PD estimate. Here we constructed DM using profiles FRAMCOHORT (Framingham Heart Study) and CHS (Cardiovascular Health Research Materials obtained NHLBI Biologic Specimen Data...
Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related are often modulated by environmental factors due to their little contribution fitness or mediated through certain endophenotypes. Identification genetic variants with pleiotropic both common complex and endophenotypes reveal potential conflicting evolutionary pressures deliver new insights into healthspan lifespan. Here, we performed meta-analyses using five...
Abstract The TOMM40‐APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 in was suggested, comparative contribution regulation weight remains elusive. We examined additive effects rs2075650 rs157580 rs429358 rs7412 coding ε2/ε3/ε4 polymorphism on mass index (BMI) age‐aggregated age‐stratified cohort‐specific cohort‐pooled analysis 27,863 Caucasians aged 20–100 years from seven longitudinal...
While longitudinal changes in biomarker levels and their impact on health have been characterized for individual markers, little is known about how overall marker profiles may change during aging affect mortality risk. We implemented the recently developed measure of physiological dysregulation based statistical distance framework stochastic process model aging, using data blood pressure, heart rate, cholesterol, glucose, hematocrit, body mass index Framingham original cohort. This allowed...
Severe COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in count during demands fast massive clonal expansion, which telomere length (TL)-dependent.We developed a model of TL-dependent expansion capacity with age virtually examined relation mortality general population.The shows that an individual average hematopoietic cell TL (HCTL) at twenty years maintains maximal until 6th decade life when this rapidly declines by than 90%...
Accumulating evidence suggests that infections may play a major role in Alzheimer's disease (AD), however, mechanism is unclear, as multiple pathways be involved. One possibility could contribute to neurodegeneration directly by promoting neuronal death. We explored relationships between history of and brain hippocampal volume (HV), biomarker neurodegeneration, subsample the UK Biobank (UKB) participants. Infectious diagnoses were based on ICD10 codes. The left/right HV was measured magnetic...