Cross-tissue comparison of epigenetic aging clocks in humans.

Epigenetic clocks are a common group of tools used to measure biological aging-the progressive deterioration of cells, tissues, and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues, but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e.

An expert consensus statement on biomarkers of ageing for use in intervention studies.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

Applications of Nanotechnology for Spatial Omics: Biological Structures and Functions at Nanoscale Resolution.

Spatial omics methods are extensions of traditional histological methods that can illuminate important biomedical mechanisms of physiology and disease by examining the distribution of biomolecules, including nucleic acids, proteins, lipids, and metabolites, at microscale resolution within tissues or individual cells. Since, for some applications, the desired resolution for spatial omics approaches the nanometer scale, classical tools have inherent limitations when applied to spatial omics analyses, and they can measure only a limited number of targets. Nanotechnology applications have been instrumental in overcoming these bottlenecks.

Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort.

Older parental age at birth is associated with increased risk of autism spectrum disorders (ASD) in offspring. Independently, shorter telomere length (TL) has also been shown to be associated with ASD in children. However, older paternal age at birth, with or without controlling for maternal age, has been associated with longer TL, a seemingly contradictory finding.

Cross-Tissue Comparison of Epigenetic Aging Clocks in Humans.

Epigenetic clocks are a common group of tools used to measure biological aging - the progressive deterioration of cells, tissues and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e.

Early life adversity is associated with differential gene expression in immune cells: A cluster-based analysis across an acute psychosocial stressor.

Elucidating mechanisms by which early-life adversity (ELA) contributes to increased disease risk is important for mitigating adverse health outcomes. Prior work has found differences in immune cell gene expression related to inflammation and mitochondrial activity. Using a within-person between-group experimental design, we investigated differences in gene expression clusters across acute psychosocial stress and no-stress conditions.

Monochrome Multiplex Quantitative PCR Telomere Length Measurement.

Telomeres are ribonucleoprotein structures at the end of all eukaryotic chromosomes that protect DNA from damage and preserve chromosome stability. Telomere length (TL) has been associated with various exposures, biological processes, and health outcomes. This article describes the monochrome multiplex quantitative polymerase chain reaction (MMqPCR) assay protocol routinely conducted in our laboratory for measuring relative mean TL from human DNA.

Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis.

Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.

Cross-tissue comparison of telomere length and quality metrics of DNA among individuals aged 8 to 70 years.

Telomere length (TL) is an important biomarker of cellular aging, yet its links with health outcomes may be complicated by use of different tissues. We evaluated within- and between-individual variability in TL and quality metrics of DNA across five tissues using a cross-sectional dataset ranging from 8 to 70 years (N = 197). DNA was extracted from all tissue cells using the Gentra Puregene DNA Extraction Kit.

Emotion-related impulsivity is related to orbitofrontal cortical sulcation.

Background: Emotion-related impulsivity (ERI) describes the trait-like tendency toward poor self-control when experiencing strong emotions. ERI has been shown to be elevated across psychiatric disorders and predictive of the onset and worsening of psychiatric syndromes. Recent work has correlated ERI scores with the neuroanatomy of the orbitofrontal cortex (OFC).

Ventral temporal and posteromedial sulcal morphology in autism spectrum disorder.

Two parallel research tracks link the morphology of small and shallow indentations, or sulci, of the cerebral cortex with functional features of the cortex and human cognition, respectively. The first track identified a relationship between the mid-fusiform sulcus (MFS) in ventral temporal cortex (VTC) and cognition in individuals with Autism Spectrum Disorder (ASD). The second track identified a new sulcus, the inframarginal sulcus (IFRMS), that serves as a tripartite landmark within the posteromedial cortex (PMC).

Telomere length and chronological age across the human lifespan: A systematic review and meta-analysis of 414 study samples including 743,019 individuals.

Telomere attrition is a proposed hallmark of aging. To evaluate the association of telomere length (TL) with chronological age across the human lifespan, we conducted a systematic review and meta-analysis of 414 study samples comprising 743,019 individuals aged 0-112 years. We examined both cross-sectional and longitudinal data, and evaluated the impact of various biological and methodological factors including sex, health status, tissue types, DNA extraction procedures, and TL measurement methods.

Biological stability of DNA methylation measurements over varying intervals of time and in the presence of acute stress.

Identifying factors that influence the stability of DNA methylation measurements across biological replicates is of critical importance in basic and clinical research. Using a within-person between-group experimental design ( = 31, number of observations = 192), we report the stability of biological replicates over a variety of unique temporal scenarios, both in the absence and presence of acute psychosocial stress, and between individuals who have experienced early life adversity (ELA) and non-exposed individuals. We found that varying time intervals, acute stress, and ELA exposure influenced the stability of repeated DNA methylation measurements.

A review and meta-analysis: Cross-tissue telomere length correlations in healthy humans.

Background And Aim: Tissue source has been shown to exert a significant effect on the magnitude of associations between telomere length and various health outcomes and exposures. The purpose of the present qualitative review and meta-analysis is to describe and investigate the impact of study design and methodological features on the correlation between telomere lengths measured in different tissues from the same healthy individual.

Methods: This meta-analysis included studies published from 1988 to 2022.

Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm), and is established to increase healthy lifespan in multiple species. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref.

Investigating the effects of maltreatment and acute stress on the concordance of blood and DNA methylation methods of estimating immune cell proportions.

Background: Immune cell proportions can be used to detect pathophysiological states and are also critical covariates in genomic analyses. The complete blood count (CBC) is the most common method of immune cell proportion estimation, but immune cell proportions can also be estimated using whole-genome DNA methylation (DNAm). Although the concordance of CBC and DNAm estimations has been validated in various adult and clinical populations, less is known about the concordance of existing estimators among stress-exposed individuals.

Immune cell dynamics in response to an acute laboratory stressor: a within-person between-group analysis of the biological impact of early life adversity.

Early life adversity (ELA) is a risk factor for early onset morbidities and mortality, a relationship that may be driven in part by immune system dysregulation. One mechanism of dysregulation that has yet to be fully examined in the context of ELA is alterations to immune cell dynamics in response to acute stress. Using a within-person between-group experimental design, we investigated stress-induced changes in immune cell populations, and how these changes may be altered in individuals with a history of ELA.

Cumulative risk exposure and child cellular aging in a Dutch low-risk community sample.

One of the proposed mechanisms linking childhood stressor exposure to negative mental and physical health outcomes in later life is cellular aging. In this prospective, longitudinal, and pre-registered study, we examined the association between a cumulative pattern of childhood risk exposure from age 6 to age 10 (i.e.

Attachment insecurity and the biological embedding of reproductive strategies: Investigating the role of cellular aging.

Evolutionary-developmental psychologists have posited that individuals who grow up in stressful rearing circumstances follow faster life history strategies, thereby increasing their chances of reproduction. This preregistered study tested this stress-acceleration hypothesis in a low-risk longitudinal sample of 193 Dutch mother-child dyads, by investigating whether infant-mother attachment insecurity at 12 months of age predicted earlier pubertal onset and more callous-unemotional traits, aggression and risk-taking about a decade later. Also evaluated were the possible mediating roles of two biomarkers of accelerated aging (i.

Obesity and accelerated epigenetic aging in a high-risk cohort of children.

New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children.

Comparing qPCR and DNA methylation-based measurements of telomere length in a high-risk pediatric cohort.

Various approaches exist to assess population differences in biological aging. Telomere length (TL) is one such measure, and is associated with disease, disability and early mortality. Yet, issues surrounding precision and reproducibility are a concern for TL measurement.

Impact of Amplification Efficiency Approaches on Telomere Length Measurement Quantitative-Polymerase Chain Reaction.

Precise determination of amplification efficiency is critical for reliable conversion of within-sample changes in fluorescence occurring on a logarithmic scale to between-sample differences in DNA content occurring on a linear scale. This endeavor is especially challenging for the telomere length (TL) quantitative-PCR (qPCR) assay, where amplification efficiency can vary between reactions targeting telomeric repeats (T) and those targeting a single-copy gene (S) to calculate TL as the T/S ratio. We compared seven different approaches toward estimating amplification efficiency, including the standard-curve method utilized by the qPCR instrument software, and alternative approaches which estimate efficiency on a reaction-by-reaction basis using the stand-alone program LinRegPCR.

Conceptual and Analytical Overlap Between Allostatic Load and Systemic Biological Aging Measures: Analyses From the National Survey of Midlife Development in the United States.

Background: Indices quantifying allostatic load (AL) and biological aging (BA) have independently received widespread use in epidemiological literature. However, little attention has been paid to their conceptual and quantitative overlap. By reviewing literature utilizing measures of AL and BA, and conducting comparative analysis, we highlight similarities and differences in biological markers employed and approach toward scale construction.

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms.

SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression.