Biology subjects

Cayo Biobank Research Unit,

Publications and source records attributed to Cayo Biobank Research Unit,.

12 recordsLinked to original sources

bioRxiv2026

Early life adversity shapes adult behavior in a free-ranging primate

Early life adversity (ELA) causes lasting psychological and behavioral consequences in humans, with parallel stress and fear responses observed in captive animals. How naturally occurring ELA shapes behavior in non-captive animals remains poorly understood. Investigating these effects across socioecological environments is important for identifying the evolutionary pressures shaping early life sensitivities, and determining whether these behavioral syndromes have deep evolutionary roots. Here, we tested the effects of eight forms of ELA on adult behavior using a large dataset (N=313 males, 346 females) from a free-ranging population of rhesus macaques (Macaca mulatta). We measured adult behaviors indicative of stress and the tenor of social interactions, including agonism, vigilance, self-directed behaviors, and affiliation. Individuals exposed to more ELA received more aggression and less grooming, were more submissive, and were less vigilant. While high status buffered the effects of ELA on grooming, it amplified effects on aggression. Our findings demonstrate that in a large sample of a free-ranging primate, early life environments impact behavior into adulthood. While some behaviors are consistent with patterns in humans and captive animals, suggesting an evolutionarily conserved ELA syndrome, other findings add new insights into the various ways individuals interact with their environment as a function of ELA.

evolutionary biology↗

bioRxiv2025

Single-cell, multi-region profiling of the macaque brain across the lifespan

Brain aging is a complex process with profound health and societal consequences. However, the molecular and cellular pathways that govern its temporal progression-along with any cell type-, region-, and sex-specific heterogeneity in such progression-remain poorly defined. Here, we present a transcriptomic atlas of 5.3 million cells from 582 samples spanning 11 brain regions of 55 rhesus macaques (29 female, 26 male), aged 5 months (early life) to 21 years (late adulthood). We annotate 12 major cell classes and 225 subclusters, including region-specific subtypes of excitatory and inhibitory neurons, astrocytes, and ependymal cells. We identify a vulnerable excitatory neuron population in the superficial cortical lamina and a cortical interneuron population that are less abundant later in life, along with subtle, region-specific, age-associated compositional differences in subpopulations of microglia and oligodendrocytes, whose detection required single-cell resolution. Finally, we chart convergent and divergent age-associated molecular signatures across brain regions and cell classes-where some of these signatures are sex-specific and could underlie sex biases in neurological disorders. We find that age-associated transcriptional programs not only overlap substantially with those seen in Alzheimers disease (AD), but also unfold along distinct temporal trajectories across brain regions, suggesting that aging and AD may share molecular roots that emerge at different life stages and in region-specific, sex-specific windows of vulnerability. This work provides a temporal, regional, and sex-stratified atlas of the aging primate brain, offering insights into cell type-specific vulnerabilities and regional heterogeneity with translational human relevance.

neuroscience↗

bioRxiv2025

The influence of captivity on cardiac structure and function across age, in rhesus macaques

BackgroundCaptive non-human primates are widely used as models of human aging, yet the conditions they live in differ markedly from their naturalistic environment. Differences between captive and free-ranging environments may impact how the cardiovascular system adapts with age, potentially confounding studies of natural aging. This study characterized age-related cardiac phenotypes in free-ranging rhesus macaques and compared these patterns with their captive-housed counterparts to assess the influence of living environment on cardiac health across the lifespan. MethodologyWe performed transthoracic echocardiography in a cross-sectional cohort of 133 free-ranging rhesus macaques (Macaca mulatta, aged 7 - 25 years, 41 % female) living on Cayo Santiago, Puerto Rico. First, we compared structural and functional cardiac parameters between young (7 - 12 years; n = 48, 60% female) and old (18-26 years, n = 33, 42% female) free-ranging macaques. We then performed an ANCOVA, with age as a covariate, to compare cardiac structural and functional parameters between free-ranging and captive-housed macaques (n = 347, aged 7 - 32 years, 71% female). ResultsIn our free-ranging cohort, older macaques had greater interventricular septal thickness and relative wall thickness (RWT) than young. Males exhibited larger left ventricular (LV) internal dimensions, wall thickness, LV mass, and LV volumes than females, but these differences were attenuated when indexed to body mass. Diastolic function was lower with advanced age in both sexes, reflected by a lower E/A ratio, reduced myocardial tissue velocities during early diastole (e') and greater myocardial tissue velocities during atrial contraction (a). Compared with captive macaques, free-ranging animals exhibited better diastolic function, including a significantly higher E/A ratio, greater e, and lower a. Captive macaques also had significantly greater relative wall thickness across age and between sexes. Conclusions and implicationsOur study provides the first comprehensive characterization of age-related cardiac differences in free-ranging rhesus macaques, which show structural and functional cardiac differences similar to those observed with human aging. Captive macaques exhibited a more pronounced age-related cardiac phenotype than their free-ranging counterparts, including thicker left ventricular walls and lower diastolic function for a given age. These findings highlight the importance of considering the ecological context when interpreting animal models of cardiovascular aging.

physiology↗

bioRxiv2025

Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques

Age and early life adversity (ELA) are both key determinants of health, but whether they target similar physiological mechanisms across the body is unknown due to limited multi-tissue datasets from well-characterized cohorts. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free ranging rhesus macaques, with records of naturally occurring ELA. We show that age-associated DNAm variation is predominantly tissue-dependent, yet tissue-specific epigenetic clocks reveal that the pace of epigenetic aging is relatively consistent within individuals. ELA effects on loci are adversity-dependent, but a given ELA has a coordinated impact across tissues. Finally, ELA targeted many of the same loci as age, but the direction of these effects varied, indicating that ELA does not uniformly contribute to accelerated age in the epigenome. ELA thus imprints a coordinated, tissue-spanning epigenetic signature that is both distinct from and intertwined with age-related change, advancing our understanding of how early environments sculpt the molecular foundations of aging and disease.

genomics↗

bioRxiv2023

Social responses to a hurricane drive greater epidemic risk

Climate change is intensifying extreme weather events, with severe implications for ecosystem dynamics. A key behavioural mechanism whereby animals may cope with such events is by increasing social cohesion to improve access to scarce resources like refuges, which in turn could exacerbate epidemic risk due to increased close contact. However, how and to what extent natural disasters affect disease risk via changes in sociality remains unexplored in animal populations. By modelling disease spread in free-living rhesus macaque groups (Macaca mulatta) before and after a hurricane, we demonstrate doubled pathogen transmission rates up to five years following the disaster, equivalent to an increase in pathogen infectivity from 10% to 20%. Moreover, the hurricane redistributed the risk of infection across the population, decreasing status-related differences found in pre-hurricane years. These findings demonstrate that natural disasters can exacerbate and homogenise epidemic risk in an animal population via changes in sociality. These observations provide unexpected further mechanisms by which extreme weather events can threaten wildlife health, population viability, and spillover to humans.

ecology↗

bioRxiv2022

Cost and benefits of being social: examining the influence of sociality on faecal parasites in free-ranging rhesus macaques

Parasites and infectious diseases constitute an important challenge to the health of group-living animals. Social contact and shared space can both increase disease transmission risk, while individual differences in social resources can help prevent infections. For example, high social status individuals and those with more or stronger social relationships may have better immunity and, thus, lower parasitic burden. To test for health trade-offs in the costs and benefits of sociality, we quantified how parasitic load varied with an individuals social status, as well as with their weak and strong affiliative relationships in a free-ranging population of rhesus macaques (Macaca mulatta). Social resources may also protect against infection under environmentally challenging situations, such as natural disasters. We additionally examined the impact of a major hurricane on the sociality-parasite relationship in this system. We found that both weak and strong proximity partners, but not grooming partners, were associated with lower protozoa infection risk. Social status was not linked to infection risk, even after the hurricane. Overall, our study highlights the buffering against infection that affiliative partners may provide, suggesting individuals can compensate for the health costs of sociality by having partners who tolerate their presence.

ecology↗

bioRxiv2022

A generalizable epigenetic clock captures aging in two nonhuman primates.

Epigenetic clocks generated from DNA methylation array data provide important insights into biological aging, disease susceptibility, and mortality risk. However, these clocks cannot be applied to high-throughput, sequence-based datasets more commonly used to study nonhuman animals. Here, we built a generalizable epigenetic clock using genome-wide DNA methylation data from 493 free-ranging rhesus macaques. Using a sliding-window approach that maximizes generalizability across datasets and species, this model predicted age with high accuracy ({+/-} 1.42 years) in held-out test samples, as well as in two independent test sets: rhesus macaques from a captive population (n=43) and wild baboons in Kenya (n=271). Our model can also be used to generate insight into the factors hypothesized to alter epigenetic aging, including social status and exposure to traumatic events. Our results thus provide a flexible tool for predicting age in other populations and species and illustrate how connecting behavioral data with the epigenetic clock can uncover social influences on biological age.

evolutionary biology↗

bioRxiv2022

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome

Humans exhibit sex differences in the prevalence of many neurodevelopmental and neurodegenerative conditions. To better understand the translatability of a critical nonhuman primate model, the rhesus macaque, we generated one of the largest multibrain region bulk transcriptional datasets for this species and characterized sex-biased gene expression patterns. We demonstrate that these patterns are similar to those in humans and are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate the rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and validate the rhesus macaque model for the study of these conditions.

neuroscience↗

bioRxiv2022

A single-cell multi-omic atlas spanning the adult rhesus macaque brain

Cataloging the diverse cellular architecture of the primate brain is crucial for understanding cognition, behavior and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas of the rhesus macaque brain. Altogether, we profiled 2.58M transcriptomes and 1.59M epigenomes from single nuclei sampled from 30 regions across the adult brain. Cell composition differed extensively across the brain, revealing cellular signatures of region-specific functions. We also identified 1.19M candidate regulatory elements, many novel, allowing us to explore the landscape of cis-regulatory grammar and neurological disease risk in a cell-type-specific manner. Together, this multi-omic atlas provides an open resource for investigating the evolution of the human brain and identifying novel targets for disease interventions.

neuroscience↗

bioRxiv2022

Ageing in a collective: The impact of ageing individuals on social network structure

Ageing affects many phenotypic traits, but its consequences for social behaviour have only recently become apparent. Social networks emerge from associations between individuals. The changes in sociality that occur as individuals get older are thus likely to impact network structure, yet this remains unstudied. Here we use empirical data from free-ranging rhesus macaques and an agent-based model to test how age-based changes in social behaviour feed up to influence: (1) an individuals level of indirect connectedness in their network; and (2) overall patterns of network structure. Our empirical analyses revealed that female macaques became less indirectly connected as they aged for some, but not all network measures examined, suggesting that indirect connectivity is affected by ageing, and that ageing animals can remain well integrated in some social contexts. Surprisingly, we did not find evidence for a relationship between age distribution and the structure of female macaque networks. We used an agent-based model to gain further understanding of the link between age-based differences in sociality and global network structure, and under which circumstances global effects may be detectable. Overall, our results suggest a potentially important and underappreciated role of age in the structure and function of animal collectives, which warrants further investigation.

animal behavior and cognition↗

bioRxiv2022

Age-related differences in ocular features of a naturalistic free-ranging population of rhesus macaques

PurposeRhesus macaques (Macaca mulatta) are the premier nonhuman primate model for studying human health and disease. We aimed to investigate if age was associated with ocular features of clinical relevance in a large cohort of free-ranging rhesus macaques from Cayo Santiago, Puerto Rico. MethodsWe evaluated 120 rhesus macaques (73 males, 47 females) aged from 0 to 29 years old (mean{+/-}SD: 12.6{+/-}6.4) from September to December, 2021. The ophthalmic evaluation included IOP assessment, corneal pachymetry, anterior segment biomicroscopy, A-Scan biometry, automated refraction, and fundus photography after pupil dilation. The effects of age on the outcome variables were investigated through multilevel mixed-effects models adjusted for sex and weight. ResultsOn average, IOP, pachymetry, axial length, and automated refraction spherical equivalent were 15.47{+/-}2.47 mmHg, 474.43{+/-}32.21 m, 19.49{+/-}1.24 mm, and 0.30{+/-}1.70 D, respectively. Age was significantly associated with pachymetry (Coef.= -1.20; 95%CI: -2.27 to -0.14; p=0.026), axial length (Coef.= 0.03; 95%CI: 0.01 to 0.05; p=0.002), and spherical equivalent (Coef.= -0.12; 95%CI: -0.22 to -0.02; p=0.015). No association was detected between age and IOP. The prevalence of cataracts in either eye was 10.83% (95% CI: 6.34 - 17.89%) and was significantly associated with age (OR= 1.20; 95%CI: 1.06 - 1.36; p=0.004). Retinal drusen in either eye was observed in 15.00% (95% CI: 9.60 - 22.68%) of the animals, which was also significantly associated with age (OR=1.14; 95%CI: 1.02 - 1.27; p=0.020). ConclusionsRhesus macaques exhibit age-related ocular associations similar to those observed in human aging, including decreased corneal thickness, increased axial length, myopic shift, and higher occurrence of cataract and retinal drusen.

systems biology↗

bioRxiv2021

Sociodemographic effects on immune cell composition in a free-ranging non-human primate.

Increasing age is associated with dysregulated immune function and increased inflammation- patterns that are also observed in individuals exposed to chronic social adversity. Yet we still know little about how social adversity impacts the immune system and how it might promote age-related diseases. Here, we investigated how immune cell diversity varied with age, sex and social adversity (operationalized as low social status) in free-ranging rhesus macaques. We found age-related signatures of immunosenescence, including lower proportions of CD20+ B cells, CD20+/CD3+ ratio, and CD4+/CD8+ T cell ratio - all signs of diminished antibody production. Age was associated with higher proportions of CD3+/CD8+ Cytotoxic T cells, CD16+/CD3-Natural Killer cells, CD3+/CD4+/CD25+ and CD3+/CD8+/CD25+ T regulatory cells, and CD14+/CD16+/HLA-DR+ intermediate monocytes, and lower levels of CD14+/CD16-/HLA-DR+ classical monocytes, indicating greater amounts of inflammation and immune dysregulation. We also found an effect of exposure to social adversity (i.e., low social status) that was sex-dependent. High-status males, relative to females, had higher CD20+/CD3+ ratios and CD16+/CD3 Natural Killer cell proportions, and lower proportions of CD8+ Cytotoxic T cells. Further, low status females had higher proportions of cytotoxic T cells than high status females, while the opposite was observed in males. High status males had higher CD20+/CD3+ ratios than low status males. Together, our study identifies immune cell types that differ by age in a human-relevant primate model animal, and demonstrates a novel link between sex-dependent immunity and social adversity.

immunology↗