Recruitment evaluation of a gerotherapeutic randomized controlled trial testing alpha-ketoglutarate in biologically older, middle-aged adults (ABLE).

Background: Gerotherapeutic interventions that optimize the health and healthspan of biologically older, yet generally healthy adults are importance for reducing healthcare costs associated with ageing populations. It remains unclear whether recruiting middle-aged individuals with an older biological age is feasible in gerotherapeutic trials. The aim is to evaluate feasibility of recruiting biologically older yet generally healthy middle-aged adults for Alpha-ketoglutarate Supplementation and BiologicaL agE in middle-aged adults (ABLE) trial.

Predictive capabilities of polygenic scores in an East-Asian population-based cohort: the Singapore Chinese health study.

Polygenic scores (PGS) are derived primarily from European population studies. It is unclear how these perform in risk predictions among East-Asians. We generated 2173 PGSs from 519 traits and assessed their associations with 58 baseline phenotypes in the Singapore Chinese Health Study, a prospective cohort of 23,622 Chinese adults residing in Singapore.

Polygenic prediction of body mass index and obesity through the life course and across ancestries.

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.

Systematic transcriptomics analysis of calorie restriction and rapamycin unveils their synergistic interaction in prolonging cellular lifespan.

Aging is a multifaceted biological process marked by the decline in both mitotic and postmitotic cellular function, often central to the development of age-related diseases. In the pursuit of slowing or even reversing the aging process, a prominent strategy of significant interest is calorie restriction (CR), also known as dietary restriction, and the potential influence of a drug called rapamycin (RM). Both CR and RM have demonstrated the capacity to extend healthspan and lifespan across a diverse array of species, including yeast, worms, flies, and mice.

Genome-wide association study reveals a novel tuberculosis susceptibility locus in multiple East Asian and European populations.

Background: Tuberculosis (TB) continues to be a leading cause of morbidity and mortality worldwide. Past genome-wide association studies (GWAS) have explored TB susceptibility across various ethnic groups, yet a significant portion of TB heritability remains unexplained.

Methods: We conducted GWAS in the Singapore Chinese and Vietnamese, followed by a comprehensive meta-analysis incorporating 4 independent East Asian datasets, resulting in a total of 11,841 cases and 197,373 population controls.

DNAm age differences between infinium methylationEPICv1 vs EPICv2 in buffy coat, PBMC, and saliva samples.

This study aims to evaluate differences between Infinium MethylationEPIC (EPICv1) and Infinium MethylationEPICv2 (EPICv2) arrays in estimating DNAm age with eleven DNAm clocks using buffy coat, peripheral blood mononuclear cell (PBMC), and saliva from 16 healthy middle-aged individuals. DNAm ages were estimated using six principal component-based (PC) clocks (PCHorvath1, PCHorvath2, PCHannum, PCPhenoAge, PCGrimAge, and PCDNAmTL) and five non-PC clocks (DunedinPACE, DNAmFit, YingCausAge, YingAdaptAge, and YingDamAge) across all biological samples. Agreement between arrays was assessed using Spearman correlation, Bland-Altman plots, and Wilcoxon Signed-Rank test.

Predictive Capabilities of Polygenic Scores in an East-Asian Population-based Cohort: The Singapore Chinese Health Study.

Background: Existing polygenic scores (PGS) are derived primarily from studies performed in European populations. It is still unclear how these perform in improving risk predictions in East-Asians.

Methods: We generated 2,173 PGSs from 519 traits and assessed their associations with 58 baseline phenotypes in the Singapore Chinese Health Study (SCHS), a prospective cohort of 23,622 middle-aged and older Chinese residing in Singapore.

The Association of Physical Function and Physical Performance With DNA Methylation Clocks in Oldest-Old Living in Singapore-The SG90 Cohort.

Deoxyribonucleic acid (DNA) methylation (DNAm) clocks estimate biological age according to DNA methylation. This study investigated the associations between measures of physical function and physical performance and 10 DNAm clocks in the oldest-old in Singapore. The SG90 cohort included a subset of community-dwelling oldest-old from the Singapore Chinese Health Study (SCHS) and Singapore Longitudinal Ageing Study (SLAS).

Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.

Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction.

Aging is an inevitable biological process that contributes to the onset of age-related diseases, often as a result of mitochondrial dysfunction. Understanding the mechanisms behind aging is crucial for developing therapeutic interventions. This study investigates the effects of curcumin on postmitotic cellular lifespan (PoMiCL) during chronological aging in yeast, a widely used model for human postmitotic cellular aging.

The Causal Effect of Adult Height on Late-Life Handgrip Strength: The Singapore Chinese Health Study.

Background: Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias.

Methods: We evaluated pairwise associations among handgrip strength, adult height, and genetically determined height (using a polygenic score [PGS] for height in a mediation framework and a 2-sample Mendelian randomization approach) by means of a multivariable regression model using a prospective cohort of Chinese living in Singapore.

Characterizing the Relationship between Expression Quantitative Trait Loci (eQTLs), DNA Methylation Quantitative Trait Loci (mQTLs), and Breast Cancer Risk Variants.

Purpose: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer.

Methods: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS).

APOE Genotype Modifies the Association between Midlife Adherence to the Planetary Healthy Diet and Cognitive Function in Later Life among Chinese Adults in Singapore.

Background: It remains unclear if adherence to the planetary healthy diet (PHD), designed to improve human and environmental health, is associated with better cognitive function in aging, and if this association differs by apolipoprotein E (APOE) genotype.

Objectives: We aimed to examine the association between the PHD pattern and risk of poor cognitive function, and to further assess whether the APOE ε4 allele could modify this association.

Methods: The study included 16,736 participants from the Singapore Chinese Health Study.

Novel Melanocortin-3 and -4 Receptor Functional Variants in Asian Children With Severe Obesity.

Context: Genetic variants in melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) genes are strongly associated with childhood obesity.

Objective: This study aims to identify and functionally characterize MC3R and MC4R variants in an Asian cohort of children with severe early-onset obesity.

Methods: Whole-exome sequencing was performed to screen for MC3R and MC4R coding variants in 488 Asian children with severe early-onset obesity (body mass index for age ≥97th percentile).

Disruption of Aldehyde Dehydrogenase 2 protects against bacterial infection.

Unlabelled: The (rs671) allele is one of the most common genetic mutations in humans, yet the positive evolutionary selective pressure to maintain this mutation is unknown, despite its association with adverse health outcomes. ALDH2 is responsible for the detoxification of metabolically produced aldehydes, including lipid-peroxidation end products derived from inflammation. Here, we demonstrate that host-derived aldehydes 4-hydroxynonenal (4HNE), malondialdehyde (MDA), and formaldehyde (FA), all of which are metabolized by ALDH2, are directly toxic to the bacterial pathogens and at physiological levels.

Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)-intervention study protocol.

Targeting molecular processes of aging will enable people to live healthier and longer lives by preventing age-related diseases. Geroprotectors are compounds with the potential to increase healthspan and lifespan. Even though many of them have been tested in animal models, the translation to humans is limited.

A five-safes approach to a secure and scalable genomics data repository.

Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud.

Polygenic risk scores for the prediction of common cancers in East Asians: A population-based prospective cohort study.

Background: To evaluate the utility of polygenic risk scores (PRSs) in identifying high-risk individuals, different publicly available PRSs for breast (n=85), prostate (n=37), colorectal (n=22), and lung cancers (n=11) were examined in a prospective study of 21,694 Chinese adults.

Methods: We constructed PRS using weights curated in the online PGS Catalog. PRS performance was evaluated by distribution, discrimination, predictive ability, and calibration.

Increased BMI and late-life mobility dysfunction; overlap of genetic effects in brain regions.

Background: How obesity earlier in life impacts upon mobility dysfunctions in late life is not well understood. Pernicious effects of excess weight on the musculoskeletal system and mobility dysfunctions are well-recognized. However, increasingly more data support the link of obesity to overall motor defects that are regulated in the brain.

Vascular smooth muscle cells in low SYNTAX scores coronary artery disease exhibit proinflammatory transcripts and proteins correlated with IL1B activation.

Background And Aims: The SYNTAX score is clinically validated to stratify number of lesions and pattern of CAD. A better understanding of the underlying molecular mechanisms influencing the pattern and complexity of coronary arteries lesions among CAD patients is needed.

Methods: Human arterial biopsies from 49 patients (16 low-SYNTAX-score (LSS, <23), 16 intermediate-SYNTAX-score (ISS, 23 to 32) and 17 high-SYNTAX-score (HSS, >32)) were evaluated using Affymetrix GeneChip® Human Genome U133 Plus 2.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.