Age-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Quantitative trait loci (QTL) of longevity identified in human and mouse are significantly colocalized, suggesting that common mechanisms are involved. However, the limited number of strains that have been used in mouse longevity studies undermines the ability to identify longevity genes. We crossed C57BL/6J mice with a new wild-derived strain, Pohn, and identified two life span QTL-Ls1 and Ls2. Interestingly, homologous human longevity QTL colocalize with Ls1. We also defined new QTL for metabolic heat production and body weight.
The diet known as caloric restriction (CR) has been known for 70 yr to extend the life span of rodents (1). CR can also extend life span in a broad range of other species as well, from unicellular organisms (2,3), to invertebrates (4) and most likely primates, as well (5). The budding yeast Saccharomyces cerevisiae is a useful model for the study of pathways that determine life span in response to dietary intake.
Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society
OBJECTIVE: Since a reduction of the insulin/IGF-1 signaling cascade extends life span in many species and IGF-1 signaling might partly mediate the effects of caloric restriction (CR), an experimental intervention for increasing longevity, the purpose of the present study was to use quantitative trait loci (QTL) analysis, an unbiased genetic approach, to identify particular regions of the genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C rats; the latter being an inbred strain of Wistar origin, considered as a model of healthy aging since it resists to age (an
Telomeres play a central role in cellular senescence and are associated with a variety of age-related disorders such as dementia, Alzheimer's disease and atherosclerosis. Telomere length varies greatly among individuals of the same age, and is heritable. Here we performed a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing leukocyte telomere length (LTL) measured by quantitative PCR in 3,665 American Indians (aged 14-93 years) from 94 large, multi-generational families.
The genetic regulation of the human epigenome is not fully appreciated. Here we describe the effects of genetic variants on the DNA methylome in human lung based on methylation-quantitative trait loci (meQTL) analyses. We report 34,304 cis- and 585 trans-meQTLs, a genetic-epigenetic interaction of surprising magnitude, including a regulatory hotspot. These findings are replicated in both breast and kidney tissues and show distinct patterns: cis-meQTLs mostly localize to CpG sites outside of genes, promoters and CpG islands (CGIs), while trans-meQTLs are over-represented in promoter CGIs.
Emerging evidence suggests that schizophrenia (SZ) susceptibility involves variation at genetic, epigenetic and transcriptome levels. We describe an integrated approach that leverages DNA methylation and gene expression data to prioritize genetic variation involved in disease. DNA methylation levels were obtained from whole blood of 260 SZ patients and 250 unaffected controls of which a subset with gene expression data was available.
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics
Genetic factors appear to be highly relevant to predicting differential risk for the development of post-traumatic stress disorder (PTSD). In a discovery sample, we conducted a genome-wide association study (GWAS) for PTSD using a small military cohort (Systems Biology PTSD Biomarkers Consortium; SBPBC, N?=?147) that was designed as a case-controlled sample of highly exposed, recently returning veterans with and without combat-related PTSD.
BACKGROUND: Genetic influence on DNA methylation is potentially an important mechanism affecting individual differences in humans. We use next-generation sequencing to assay blood DNA methylation at approximately 4.5 million loci, each comprising 2.9 CpGs on average, in 697 normal subjects. Methylation measures at each locus are tested for association with approximately 4.5 million single nucleotide polymorphisms (SNPs) to exhaustively screen for methylation quantitative trait loci (meQTLs).
