Biology subjects

Quillen, E. E.

Publications and source records attributed to Quillen, E. E..

9 recordsLinked to original sources

bioRxiv2026

Integrative Multi-Omics Analysis Reveals Molecular Signatures of Age-Related Decline in Vervet Leg Skeletal Muscle

Age-related decline in skeletal muscle function, often manifesting as slower gait speed, contributes significantly to frailty and loss of independence. To uncover the molecular basis of this decline, we investigated coordinated changes across the transcriptome, miRNome, and methylome in vastus lateralis muscle from female vervet monkeys (Chlorocebus aethiops sabaeus), contrasting middle-aged animals with normal gait speed versus older animals with declining gait speed. Through multi-omics integration, we identified a molecular signature that sharply distinguishes these two groups. This signature involves key regulatory molecules, including miR-181a-5p, miR-320b and miR-425 control of SYNCRIP, miR-193b-3p regulation of MCL1 and PLAU, as well as a multi-omic regulatory network governing ZNF274 and ANP32E gene expression, and altered levels of mRNAs such as VEZT. Functional annotation implicates miRNA signatures with inverse expression of their mRNA targets operating within systems of skeletal muscle biology, metabolism, and potential immune-inflammation mechanisms. Collectively, these findings reveal an interconnected network of epigenetic, post-transcriptional, and transcriptional alterations associated with impaired muscle function during aging. This molecular signature provides novel insights into potential mechanisms driving sarcopenia and highlights specific molecules as potential targets for interventions aimed at preserving muscle health.

bioinformatics↗

bioRxiv2026

Developing And Internally Validating AI-Based Aging Resilience Biomarkers in Non-Human Primates

Quantifying biological aging is crucial for understanding functional decline before the onset of morbidity. While many accelerated aging and frailty measures based on clinical data exist for humans and several for rodent models of aging, there are few options for non-human primates (NHPs). NHP clinical data has several unique features including a lack of clinically delineated normative values for features and variability in data collection over long lifespans. There are also wide discrepancies in the number of available clinical measures and number of animals across data sets. To address these challenges, we developed and validated "Aging Resilience" (AR) metrics using longitudinal, routine clinical data from two distinct non-human primate cohorts: 4,328 baboons and 281 rhesus macaques. We trained five computational models--including Linear Mixed-Effects Models, Random Forest, and Recurrent Neural Networks (RNN)--to predict chronological age, subsequently deriving AR metrics that represent the velocity (Rate of Aging) and cumulative burden (Normalized Cumulative Aging) of physiological deviation. While linear models achieved high precision in predicting chronological age (test R2 up to 0.99), they correlated poorly with actual lifespan. In contrast, AR metrics derived from non-linear models (RNN and Random Forest) displayed strong predictive validity for mortality (Pearsons r > 0.8). These findings highlight a critical paradox: models that best predict chronological age do not necessarily capture the biological resilience determining healthspan. This study establishes a scalable framework for monitoring biological aging in translational models using standard veterinary records.

bioinformatics↗

bioRxiv2024

Comparative lifespan and healthspan of nonhuman primate species common to biomedical research

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing strict inclusion criteria, primary results are based on 12,269 NHP that survived to adulthood and died of natural/health-related causes. A secondary analysis was completed for 32,616 NHP that died of any cause. Results show a pattern of reduced male survival among catarrhines (African and Asian primates), especially macaques, but not platyrrhines (Central and South American primates). For many species, median lifespans were lower than previously reported. An important consideration is that these analyses may offer a better reflection of healthspan than lifespan since research NHP are typically euthanized for humane welfare reasons before their natural end of life. This resource represents the most comprehensive characterization of sex-specific lifespan and age-at-death distributions for 12 biomedically relevant species, to date. These results clarify relationships among NHP ages and provide a valuable resource for the aging research community, improving human-NHP age equivalencies, informing investigators of expected survival rates, providing a metric for comparisons in future studies, and contributing to understanding of factors driving lifespan differences within and among species.

physiology↗

bioRxiv2021

Circulating miRNAs associated with bone mineral density in healthy adult baboons.

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and circulate in the blood, making them attractive biomarkers of disease state for tissues like bone that are challenging to interrogate directly. Here we report on five miRNAs - miR-197-3p, miR-320a, miR-320b, miR-331-5p, and miR-423-5p - that are associated with bone mineral density (BMD) in 147 healthy adult baboons. These baboons range in age from 15 to 25 years (45 to 75 human equivalent years) and were 65% female with a broad range of BMDs including a minority of osteopenic individuals. miRNAs were generated via RNA sequencing from buffy coats collected at necropsy and areal BMD evaluated via DXA of the lumbar vertebrae post-mortem. Differential expression analysis controlled for the underlying pedigree structure of these animals to account for genetic variation which may be driving miRNA abundance and BMD values. While many of these miRNAs have been associated with risk of human osteoporosis, this finding is of interest because the cohort represent a model of normal aging and bone metabolism rather than a disease cohort. The replication of miRNA associations with osteoporosis or other bone metabolic disorders in animals with healthy BMD suggests an overlap in normal variation and disease states. We suggest that these miRNAs are involved in the regulation of cellular proliferation, apoptosis, and protein composition in the extracellular matrix throughout life. However, age-related dysregulation of these systems may lead to disease causing associations of the miRNAs among individuals with clinically defined disease.

genomics↗

bioRxiv2020

An evolutionary perspective of DNA methylation patterns in skeletal tissues using a nonhuman primate model of osteoarthritis

ObjectiveEpigenetic factors, such as DNA methylation, play an influential role in the development of the degenerative joint disease osteoarthritis (OA). These molecular mechanisms have been heavily studied in humans, and although OA affects several other animals in addition to humans, few efforts have taken an evolutionary perspective. This study explores the evolution of OA epigenetics by assessing the relationship between DNA methylation variation and knee OA development in baboons (Papio spp.) and by comparing these findings to human OA epigenetic associations. MethodsGenome-wide DNA methylation patterns were identified in bone and cartilage of the right distal femora from 56 pedigreed, adult baboons (28 with and 28 without knee OA) using the Illumina Infinium MethylationEPIC BeadChip. ResultsSeveral significantly differentially methylated positions (DMPs) and regions (DMRs) were found between tissue types. Substantial OA-related differential methylation was also identified in cartilage, but not in bone, suggesting that cartilage epigenetics may be more influential in OA than bone epigenetics. Additionally, some genes containing OA-related DMPs overlap with and display methylation patterns similar to those previously identified in human OA, revealing a mixture of evolutionarily conserved and divergent OA-related methylation patterns in primates. ConclusionsOverall, these findings reinforce current etiological perspectives of OA and enhance our evolutionary understanding of epigenetic mechanisms associated with OA. This work further establishes baboons as a valuable nonhuman primate model of OA, and continued investigations in baboons will help to disentangle the molecular mechanisms contributing to OA and their evolutionary histories.

genomics↗

bioRxiv2020

Insights into the genetic architecture of the human face

The human face is complex and multipartite, and characterization of its genetic architecture remains intriguingly challenging. Applying GWAS to multivariate shape phenotypes, we identified 203 genomic regions associated with normal-range facial variation, 117 of which are novel. The associated regions are enriched for both genes relevant to craniofacial and limb morphogenesis and enhancer activity in cranial neural crest cells and craniofacial tissues. Genetic variants grouped by their contribution to similar aspects of facial variation show high within-group correlation of enhancer activity, and four SNP pairs display evidence of epistasis, indicating potentially coordinated actions of variants within the same cell types or tissues. In sum, our analyses provide new insights for understanding how complex morphological traits are shaped by both individual and coordinated genetic actions.

genetics↗

bioRxiv2019

Intra- and Inter-Specific Investigations of Skeletal DNA Methylation Patterns and Femur Morphology in Nonhuman Primates

ObjectivesEpigenetic mechanisms influence the development and maintenance of complex phenotypes and may also contribute to the evolution of species-specific phenotypes. With respect to skeletal traits, little is known about the gene regulation underlying these hard tissues or how tissue-specific patterns are associated with bone morphology or vary among species. To begin exploring these topics, this study evaluates one epigenetic mechanism, DNA methylation, in skeletal tissues from five nonhuman primate species which display anatomical and locomotor differences representative of their phylogenetic groups. Materials and MethodsFirst, we test whether intra-specific variation in skeletal DNA methylation is associated with intra-specific variation in femur morphology. Second, we identify inter-specific differences in DNA methylation and assess whether these lineage-specific patterns may have contributed to species-specific morphologies. Specifically, we use the Illumina Infinium MethylationEPIC BeadChip to identify DNA methylation patterns in femur trabecular bone from baboons (n=28), macaques (n=10), vervets (n=10), chimpanzees (n=4), and marmosets (n=6). ResultsSignificant differentially methylated positions (DMPs) were associated with a subset of morphological variants, but these likely have small biological effects and may be confounded by other variables associated with morphological variation. Conversely, several species-specific DMPs were identified, and these are found in genes enriched for functions associated with complex skeletal traits. DiscussionOverall, these findings reveal that while intra-specific epigenetic variation is not readily associated with skeletal morphology differences, some inter-specific epigenetic differences in skeletal tissues exist and may contribute to evolutionarily distinct phenotypes. This work forms a foundation for future explorations of gene regulation and skeletal trait evolution in primates.

genomics↗

bioRxiv2017

Assessment of DNA methylation patterns in the bone and cartilage of a nonhuman primate model of osteoarthritis

ObjectiveOsteoarthritis (OA) impacts humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA.\n\nDesignTrabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, five with and five without knee OA. The Infinium HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation patterns in these tissues.\n\nResultsApproximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the two filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues.\n\nConclusionsOverall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.

genetics↗

bioRxiv2017

Recent Regulatory Changes Shaped the Human Facial and Vocal Anatomy

SummaryRegulatory changes are broadly accepted as key drivers of phenotypic divergence. However, identifying regulatory changes that underlie human-specific traits has proven very challenging. Here, we use 63 DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes affecting the face and vocal tract went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-affecting genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.View Full Text

evolutionary biology↗