Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetic associations for two biological age measures point to distinct aging phenotypes.

ABSTRACT: Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome-wide association scans of two age-adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers (Levine et al., 2018; Levine, 2013) in European-descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein-coding SNPs, PhenoAgeAccel-rs429358 (APOE e4 determinant) (p = 1.50 × 10^-72 ); BioAgeAccel-rs7412 (APOE e2 determinant) (p = 3.16 × 10^-60 ). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogeneous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition.

SUBMITTER: Kuo CL

PROVIDER: S-EPMC8208797 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Major aging-associated RNA expressions change at two distinct age-positions.

Project description:BACKGROUND: Genome-wide expression profiles are altered during biological aging and can describe molecular regulation of tissue degeneration. Age-regulated mRNA expression trends from cross-sectional studies could describe how aging progresses. We developed a novel statistical methodology to identify age-regulated expression trends in cross-sectional datasets. RESULTS: We studied six cross-sectional RNA expression profiles from different human tissues. Our methodology, capable of overcoming technical and genetic background differences, identified an age-regulation in four of the tissues. For the identification of expression trends, five regression models were compared and the quadratic model was found as the most suitable for this study. After k-means clustering of the age-associated probes, expression trends were found to change at two major age-positions in brain cortex and in Vastus lateralis muscles. The first age-position was found to occur during the fifth decade and a later one during the eighth decade. In kidney cortex, however, only one age-position was identified correlating with a late age-position. Functional mapping of genes at each age-position suggests that calcium homeostasis and lipid metabolisms are initially affected and subsequently, in elderly mitochondria, apoptosis and hormonal signaling pathways are affected. CONCLUSIONS: Our results suggest that age-associated temporal changes in human tissues progress at distinct age-positions, which differ between tissues and in their molecular composition.

| S-EPMC3930826 | biostudies-literature

Comparing Biological Age Estimates Using Domain-Specific Measures From the Canadian Longitudinal Study on Aging.

Project description:Many studies have shown that estimates of biological age (BA) can predict health-related outcomes in older adults. Often, researchers employ multiple measures belonging to a variety of biological/physiological systems, and assess the validity of BA estimates by how well they approximate chronological age (CA). However, it is not clear whether this is the best approach for judging a BA estimate, or whether certain groups of measures are more informative to this end. Using data from the Canadian Longitudinal Study on Aging, we composed panels of biological measures based on the physiological systems/domains they belong to (blood, organ function, physical/cognitive performance), and also composed a panel of measures that optimized the association of BA with CA. We then compared BA estimates for each according to their association with CA and health-related outcomes, including frailty, multimorbidity, chronic condition domains, disability, and health care utilization. Although BA estimated using all 40 measures (r = 0.74) or our age-optimized panel (r = 0.77) most closely approximated CA, the strength of associations to health-related outcomes was comparable or weaker than that of our panel composed only of physical performance measures (CA r = 0.59). All BA estimates were significantly associated to the outcomes considered, with exception to the neurological and musculoskeletal disease domains, and only varied slightly by sex. In summary, while the approximation of CA is important to consider when estimating BA, the strength of associations to prospective outcomes may be of greater importance. Hence, the context in which BA is estimated should be influenced by an investigator's specific research goals.

| S-EPMC7812432 | biostudies-literature

A transcriptome-based single-cell biological age model and resource for tissue-specific aging measures.

Project description:Accurately measuring biological age is crucial for improving healthcare for the elderly population. However, the complexity of aging biology poses challenges in how to robustly estimate aging and interpret the biological significance of the traits used for estimation. Here we present SCALE, a statistical pipeline that quantifies biological aging in different tissues using explainable features learned from literature and single-cell transcriptomic data. Applying SCALE to the "Mouse Aging Cell Atlas" (Tabula Muris Senis) data, we identified tissue-level transcriptomic aging programs for more than 20 murine tissues and created a multitissue resource of mouse quantitative aging-associated genes. We observe that SCALE correlates well with other age indicators, such as the accumulation of somatic mutations, and can distinguish subtle differences in aging even in cells of the same chronological age. We further compared SCALE with other transcriptomic and methylation "clocks" in data from aging muscle stem cells, Alzheimer's disease, and heterochronic parabiosis. Our results confirm that SCALE is more generalizable and reliable in assessing biological aging in aging-related diseases and rejuvenating interventions. Overall, SCALE represents a valuable advancement in our ability to measure aging accurately, robustly, and interpretably in single cells.

| S-EPMC10547252 | biostudies-literature

Common genetic associations between age-related diseases

Project description: Not available

| S-BSST407 | biostudies-other

Brain aging comprises many modes of structural and functional change with distinct genetic and biophysical associations.

Project description:Brain imaging can be used to study how individuals' brains are aging, compared against population norms. This can inform on aspects of brain health; for example, smoking and blood pressure can be seen to accelerate brain aging. Typically, a single 'brain age' is estimated per subject, whereas here we identified 62 modes of subject variability, from 21,407 subjects' multimodal brain imaging data in UK Biobank. The modes represent different aspects of brain aging, showing distinct patterns of functional and structural brain change, and distinct patterns of association with genetics, lifestyle, cognition, physical measures and disease. While conventional brain-age modelling found no genetic associations, 34 modes had genetic associations. We suggest that it is important not to treat brain aging as a single homogeneous process, and that modelling of distinct patterns of structural and functional change will reveal more biologically meaningful markers of brain aging in health and disease.

| S-EPMC7162660 | biostudies-literature

Alcohol Consumption and Methylation-Based Measures of Biological Age.

Project description:Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with the incidence of diseases and death, less is known about how it is related to lifestyle behaviors. Among 2316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration. Recent average alcohol consumption was defined as the mean number of drinks consumed per week within the past year; lifetime average consumption was estimated as the mean number of drinks per year drinking. Whole-blood genome-wide DNA methylation was measured with HumanMethylation450 BeadChips and used to assess 4 epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) and their corresponding metrics of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, and GrimAgeAccel). Although alcohol consumption showed little association with most age acceleration metrics, both lifetime and recent average consumption measures were positively associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β = 0.30 years, 95% confidence interval [CI]: 0.11, 0.48, p = .002; recent, per additional 5 drinks/week: β = 0.19 years, 95% CI: 0.01, 0.37, p = .04). In a mutually adjusted model, only average lifetime alcohol consumption remained associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β = 0.27 years, 95% CI: 0.04, 0.50, p = .02; recent, per 5 additional drinks/week: β = 0.05 years, 95% CI: -0.16, 0.26, p = .64). Although alcohol use does not appear to be strongly associated with biological age measured by most epigenetic clocks, lifetime average consumption is associated with higher biological age assessed by the GrimAge epigenetic clock.

| S-EPMC8599006 | biostudies-literature

Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups

Project description:Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, Pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.

| EGAS00001006402 | EGA

Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups

Project description:Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.

2023-09-20 | GSE210353 | GEO

Age Group Differences in Perceived Age Discrimination: Associations With Self-Perceptions of Aging.

Project description:Background and objectivesFrom midlife onwards, age stereotypes increasingly underlie social judgments and contribute to age-based discrimination. Whereas many studies compare differences between young and older adults in reports of age discrimination or sensitivity to age stereotypes, few consider age group differences among adults over 50. We form subgroups corresponding to social age group membership (early midlife, late midlife, young old, oldest old) and examine differences in reported experiences of everyday age discrimination and associations with self-perceptions of aging.Research design and methodUsing cross-sectional and longitudinal data from the Health and Retirement Study (HRS: N = 15,071; M Age = 68, range 50-101), multivariate logistic regression was used to examine experiences of everyday discrimination attributed to age, and associations between age discrimination and self-perceptions of aging, in four age groups: early midlife, late midlife, young old, oldest old.ResultsPeople in the early midlife group (aged 50-59) reported more experiences of unfair treatment than the older age groups but were less likely to attribute their experiences to age discrimination. After controlling for covariates, individuals in all age groups who perceived their own aging positively were less likely to report experiences of age discrimination. The magnitude of this effect, however, was greatest in the early midlife group.Discussion and implicationsFindings support proposals that midlife is a pivotal life period when individuals adjust to life events and social role transitions. Future longitudinal studies will provide further insight into whether positive self-perceptions of aging are especially important in this phase of the life course.

| S-EPMC5881655 | biostudies-literature

Distinct Biological Phenotypes of Marburg and Ravn Virus Infection in Macaques.

Project description:Filoviruses are among the most pathogenic infectious agents known to human, with high destructive potential, as evidenced by the recent Ebola virus epidemic in West Africa. As members of the filovirus family, marburgviruses have caused similar devastating outbreaks, albeit with lower case numbers. In this study we compare the pathogenesis of Ravn virus (RAVV) and Marburg virus (MARV) strains Angola, Musoke, and Ozolin in rhesus and cynomolgus macaques, the 2 nonhuman primate species most commonly used in filovirus research. Our results reveal the most pathogenic MARV strain to be Angola, followed by Musoke, whereas Ozolin is the least pathogenic. We also demonstrate that RAVV is highly pathogenic in cynomolgus macaques but less pathogenic in rhesus macaques. Our results demonstrate a preferential infection of endothelial cells by MARVs; in addition, analysis of tissue samples suggests that lymphocyte and hepatocyte apoptosis might play a role in MARV pathogenicity. This information expands our knowledge about pathogenicity and virulence of marburgviruses.

| S-EPMC6249580 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data