Activity budget of a group of black-horned capuchin monkeys (Sapajus nigritus) in an urban environment / Orçamento de atividades de um grupo de macacos-prego-pretos (Sapajus nigritus) em ambiente urbano

Urban growth and human impacts on the environment have forced animals to adjust to habitat fragmentation and reduced home ranges. Capuchin monkeys are known for their great social and behavioral flexibility, occupying even highly urbanized environments in a way that the time budget of this primate in synanthropic situation may be affected by the area they inhabit. This study aims to analyze the activity budget of a group of Sapajus nigritus living in an anthropized area, 1) comparing the behavioral frequencies in urbanized areas and forest fragments; 2) comparing behavioral frequencies in different sex-age classes. During the study, the number of individuals ranged from 35 to 40 individuals identified based on sex-age classes. Behavioral data were collected using the instantaneous scan sampling method, for two minutes with eight-minute intervals. We obtained 319 scans over 28 days, distributed between November 2021 and June 2022, with eight hours per day. We compared the behaviors different areas and between sex-age classes using the Kruskal-Wallis's test. Overall, the group performed a higher frequency of traveling (21.22%), followed by foraging (18.07%), feeding (16.57%) and vigilance (15.61%). The frequency of behaviors varied between areas, with vigilance, social, resting, interaction with humans and self-activity more frequent in urbanized areas compared to forest fragments. We also found variation between the sex-age classes, primarily with juveniles foraging more and adults performing more vigilance. The differences in the behaviors performed by the group express the behavioral flexibility of S. nigritus, adapting its activity pattern according to the area occupied.

O crescimento urbano e os impactos humanos no ambiente forçaram os animais a se adaptarem à fragmentação de hábitat e à redução da área de vida. Os macacos-prego são conhecidos por sua flexibilidade social e comportamental, ocupando até mesmo ambientes altamente urbanizados, sendo que seu padrão de atividades pode ser afetado pela área que habitam. Este estudo teve como objetivo analisar o padrão de atividades de um grupo de Sapajus nigritus vivendo em área antropizada, com base em: 1) comparação das frequências comportamentais em áreas urbanizadas e fragmentos florestais; e 2) comparação das frequências comportamentais em diferentes classes sexo-etárias. Durante o estudo, o número de indivíduos variou entre 35 e 40 indivíduos, identificados a partir de classes sexo-etárias. Os dados comportamentais foram coletados pelo método scan sampling, durante dois minutos com intervalo de oito minutos. Foram obtidos 319 scans ao longo de 28 dias (entre novembro de 2021 e junho de 2022), por oito horas diárias. Comparamos os comportamentos em diferentes áreas e entre classes sexo-etárias através do teste de Kruskal-Wallis. Em geral, o grupo apresentou frequência maior de deslocamento (21,22%), seguido de forrageio (18,07%), alimentação (16,57%) e vigilância (15,61%). A frequência dos comportamentos variou entre áreas (vigilância, social, descanso, interação com humanos e autoatividade foram mais frequentes em áreas urbanizadas) e classes sexo--etárias (principalmente com os juvenis forrageando mais e os adultos realizando mais vigilância). As diferenças nos comportamentos realizados pelo grupo expressam a flexibilidade comportamental de S. nigritus, adaptando seu padrão de atividade conforme a área ocupada.

Laminar organization of visual responses in core and parabelt auditory cortex.

Audiovisual (AV) interaction has been shown in many studies of auditory cortex. However, the underlying processes and circuits are unclear because few studies have used methods that delineate the timing and laminar distribution of net excitatory and inhibitory processes within areas, much less across cortical levels. This study examined laminar profiles of neuronal activity in auditory core (AC) and parabelt (PB) cortices recorded from macaques during active discrimination of conspecific faces and vocalizations. We found modulation of multi-unit activity (MUA) in response to isolated visual stimulation, characterized by a brief deep MUA spike, putatively in white matter, followed by mid-layer MUA suppression in core auditory cortex; the later suppressive event had clear current source density concomitants, while the earlier MUA spike did not. We observed a similar facilitation-suppression sequence in the PB, with later onset latency. In combined AV stimulation, there was moderate reduction of responses to sound during the visual-evoked MUA suppression interval in both AC and PB. These data suggest a common sequence of afferent spikes, followed by synaptic inhibition; however, differences in timing and laminar location may reflect distinct visual projections to AC and PB.

Pongo's ecological diversity from dental macrowear analysis.

OBJECTIVES: Orangutans are found in tropical rainforests of Borneo (Pongo pygmaeus) and Sumatra (Pongo abelii and Pongo tapanuliensis), and they are primarily considered frugivorous species. However, ecological studies reported differences in feeding behavior between these species. P. pygmaeus spend more time feeding on low-quality foods, such as bark and tough vegetation than do P. abelii. The aim of this study is to investigate if there is any geographic variation in molar macrowear pattern between the two species. METHODS: We analyzed the macrowear pattern of second mandibular molars of 58 orangutan specimens combining dental topographic measurements (occlusal relief index, percentage of dentine exposure, and percentage of enamel wear) with the occlusal fingerprint analysis method. RESULTS: The molar macrowear patterns of P. abelii and P. pygmaeus show no significant differences in most of the variables examined in this study. While P. pygmaeus molars are generally characterized by flatter occlusal morphology with slightly larger crushing and grinding areas than those of P. abelii, these differences are not statistically significant. However, we do observe a more variable wear in P. pygmaeus. CONCLUSIONS: Similarities in molar macrowear patterns between the two species could be linked to overlapping long-term diets, primarily composed of ripe and pulpy fruits. Dental macrowear is a cumulative process that occurs during the individual's lifetime, and it may be difficult to detect seasonal changes through its examination. Future studies could integrate tooth micro- and macrowear data for a better understanding of primate dental ecology.

Profound cellular defects attribute to muscular pathogenesis in the rhesus monkey model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutations in the DMD gene. Muscle fibers rely on the coordination of multiple cell types for repair and regenerative capacity. To elucidate the cellular and molecular changes in these cell types under pathologic conditions, we generated a rhesus monkey model for DMD that displays progressive muscle deterioration and impaired motor function, mirroring human conditions. By leveraging these DMD monkeys, we analyzed freshly isolated muscle tissues using single-cell RNA sequencing (scRNA-seq). Our analysis revealed changes in immune cell landscape, a reversion of lineage progressing directions in fibrotic fibro-adipogenic progenitors (FAPs), and TGF-ß resistance in FAPs and muscle stem cells (MuSCs). Furthermore, MuSCs displayed cell-intrinsic defects, leading to differentiation deficiencies. Our study provides important insights into the pathogenesis of DMD, offering a valuable model and dataset for further exploration of the underlying mechanisms, and serves as a suitable platform for developing and evaluating therapeutic interventions.

Age- and size-related changes in hind limb muscles in two baboon species (Papio anubis and P. papio).

Body size has an impact on all biological functions and analyzing how body size impacts functional traits such as locomotion is critical. Body size does not only vary across species but also during ontogeny. Indeed, juvenile animals are often at a competitive disadvantage due to their smaller absolute size. Consequently, understanding size- and age-related changes in the locomotor system is critical for our understanding of adult phenotypes. Here, we address this question by exploring growth of the hind limb muscles in two species of closely related baboons that differ in their ecology, the olive baboon, Papio Anubis, the Guinea baboon, and Papio papio. To do so, we dissected 40 P. anubis and 10 P. papio and measured the mass and physiological cross-sectional area (PCSA) of the hind limb muscles. Our results showed no sexual differences in size- or age-related growth patterns, but did show differences between species. Whereas the scaling of muscle mass and PCSA was largely isometric in P. anubis, allometric scaling was more common in P. papio. Despite these differences between species, the knee extensors and external rotators at the knee scaled with positive allometry in both species highlighting their important role during adult locomotion. Although life-history data for P. papio are scarce, we suggest that differences between species may be associated with differences in adult body size and age of locomotor independence between species.

The response of gray mouse lemurs to acute caloric restriction before reproduction supports the "Thrifty Female Hypothesis".

The Thrifty Female Hypothesis states that females preserve more of their energy reserves during winter than males because of the sex-specific time frame of energy allocation for reproduction. As males reactivate their reproductive axis before the mating period, while females mainly allocate energy during gestation and lactation, we hypothesized that males would have to use shorter torpor bouts and longer periods of normothermic activity to promote spermatogenesis during winter, a period of low food availability. Here, we applied an acute two-week 80% caloric restriction in male and female gray mouse lemurs shortly before the mating period. We found evidence of thriftier phenotypes in wintering females, which performed deeper and longer torpor bouts than males and ultimately lost less body mass. Our results thus support the thrifty female hypothesis in a seasonally breeding primate and reinforce the concept of a sex-biased trade-off in using torpor, which might ultimately benefit reproduction and survival.

The subthalamic nucleus contributes causally to perceptual decision-making in monkeys.

The subthalamic nucleus (STN) plays critical roles in the motor and cognitive function of the basal ganglia (BG), but the exact nature of these roles is not fully understood, especially in the context of decision-making based on uncertain evidence. Guided by theoretical predictions of specific STN contributions, we used single-unit recording and electrical microstimulation in the STN of healthy monkeys to assess its causal, computational roles in visual-saccadic decisions based on noisy evidence. The recordings identified subpopulations of STN neurons with distinct task-related activity patterns that related to different theoretically predicted functions. Microstimulation caused changes in behavioral choices and response times that reflected multiple contributions to an 'accumulate-to-bound'-like decision process, including modulation of decision bounds and evidence accumulation, and to non-perceptual processes. These results provide new insights into the multiple ways that the STN can support higher brain function.

Radiation Signature in Plasma Metabolome of Total-Body Irradiated Nonhuman Primates and Clinical Patients.

In the last decade, geopolitical instability across the globe has increased the risk of a large-scale radiological event, when radiation biomarkers would be needed for an effective triage of an irradiated population. Ionizing radiation elicits a complex response in the proteome, genome, and metabolome and hence can be leveraged as rapid and sensitive indicators of irradiation-induced damage. We analyzed the plasma of total-body irradiated (TBI) leukemia patients (n = 24) and nonhuman primates (NHPs; n = 10) before and 24 h after irradiation, and we performed a global metabolomic study aiming to provide plasma metabolites as candidate radiation biomarkers for biological dosimetry. Peripheral blood samples were collected according to the appropriate ethical approvals, and metabolites were extracted and analyzed by liquid chromatography mass spectrometry. We identified an array of metabolites significantly altered by irradiation, including bilirubin, cholesterol, and 18-hydroxycorticosterone, which were detected in leukemia patients and NHPs. Pathway analysis showed overlapping perturbations in steroidogenesis, porphyrin metabolism, and steroid hormone biosynthesis and metabolism. Additionally, we observed dysregulation in bile acid biosynthesis and tyrosine metabolism in the TBI patient cohort. This investigation is, to our best knowledge, among the first to provide valuable insights into a comparison between human and NHP irradiation models. The findings from this study could be leveraged for translational biological dosimetry.

Design, Fabrication, and Characterization of Capacitive Micromachined Ultrasonic Transducers for Transcranial, Multifocus Neurostimulation.

In a recent study using 3-D fullwave simulations, it was shown for a nonhuman primate model that a helmet-shaped 3D array of 128 transducer elements can be assembled for neurostimulation in an optimized configuration with the accommodation of an imaging aperture. Considering all acoustic losses, according to this study, for a nonhuman primate skull, the assembly of the proposed transducers was projected to produce sufficient focusing gain in two different focal positions at deep and shallow brain regions, thus providing sufficient acoustic intensity at these distinct focal points for neural stimulation. This array also has the ability to focus on multiple additional brain regions. In the work presented here, we designed and fabricated a single 15 mm diameter capacitive micromachined ultrasonic transducer (CMUT) element operating at 800 kHz central frequency with a 480 kHz 3 dB bandwidth, capable of producing a 190 kPa peak negative pressure (PNP) on the surface. The corresponding projected transcranial spatial peak pulse average intensity (ISPPA) was 28 Wcm-2, and the mechanical index (MI) value was 1.1 for an array of 128 of these elements.

Sleep dysfunction and gut dysbiosis related amino acids metabolism disorders in cynomolgus monkeys after middle cerebral artery occlusion.

INTRODUCTION: This study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model. METHODS: Twenty adult male cynomolgus monkeys were divided into the sham (n = 4), middle cerebral artery occlusion (MCAO, n = 5), MCAO + FMT (n = 3), and donor (n = 8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12. RESULTS: At postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3 ± 3.2 % vs 91.3 ± 2.5 %, 79.0 ± 3.75 % vs 90.8 ± 3.2 %, and 69.5 ± 4.8 % vs 90.5 ± 2.7 %; all P < 0.05), lower relative abundance of Lactobacillus (all P < 0.05), and reduced GABA concentrations in the CSF (317.3 ± 30.6 nmol/L vs 437.7 ± 25.6 nmol/L, 303.1 ± 48.9 nmol/L vs 4 40.9 ± 37.8 nmol/L, and 337.9 ± 49.4 nmol/L vs 457.4 ± 39.2 nmol/L; all P < 0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7 ± 1.1 % vs 79.0 ± 3.75 %, and 84.1 ± 2.0 % vs 69.5 ± 4.8 %; both P < 0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1 ± 25.4 nmol/L vs 303.1 ± 48.9 nmol/L, P < 0.05) was higher in the MCAO+FMT group than in the MCAO group. CONCLUSIONS: Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and Gln in the CSF and can be ameliorated using FMT.

FcRn-enhancing mutations lead to increased and prolonged levels of the HIV CCR5-blocking monoclonal antibody leronlimab in the fetuses and newborns of pregnant rhesus macaques.

Prenatal administration of monoclonal antibodies (mAbs) is a strategy that could be exploited to prevent viral infections during pregnancy and early life. To reach protective levels in fetuses, mAbs must be transported across the placenta, a selective barrier that actively and specifically promotes the transfer of antibodies (Abs) into the fetus through the neonatal Fc receptor (FcRn). Because FcRn also regulates Ab half-life, Fc mutations like the M428L/N434S, commonly known as LS mutations, and others have been developed to enhance binding affinity to FcRn and improve drug pharmacokinetics. We hypothesized that these FcRn-enhancing mutations could similarly affect the delivery of therapeutic Abs to the fetus. To test this hypothesis, we measured the transplacental transfer of leronlimab, an anti-CCR5 mAb, in clinical development for preventing HIV infections, using pregnant rhesus macaques to model in utero mAb transfer. We also generated a stabilized and FcRn-enhanced form of leronlimab, termed leronlimab-PLS. Leronlimab-PLS maintained higher levels within the maternal compartment while also reaching higher mAb levels in the fetus and newborn circulation. Further, a single dose of leronlimab-PLS led to complete CCR5 receptor occupancy in mothers and newborns for almost a month after birth. These findings support the optimization of FcRn interactions in mAb therapies designed for administration during pregnancy.

The Role of Behavioral Management in Enhancing Clinical Care and Efficiency, Minimizing Social Disruption, and Promoting Welfare in Captive Primates.

Medical procedures necessary for routine care can induce stress in both the veterinary and human clinical situations. In the research environment, nonhuman primates undergo procedures like physical examination, blood sampling, and intravenous drug or fluid administration either as a part of routine veterinary care or during the modeling of clinical disease and interventions under study. Behavioral management techniques, such as training for cooperation, allow caregivers to train primates to voluntarily engage in various medical procedures. This approach reduces stress and anxiety associated with necessary procedures, thereby enhancing efficiency and minimizing the invasiveness of medical care. Consequently, veterinary evaluation and care can be provided without compromise, resulting in enhanced clinical outcomes and overall better health. In this study, we explored the impact of the behavioral management program implemented at our center on a subset of animals undergoing routine veterinary care, focusing on the overall experience, including animal welfare, scientific rigor, and efficiency in terms of economics and time. We investigated its impact on key factors, such as the total procedure and recovery time, incidence of side effects, and welfare indicators, revealing a significant positive influence on animal care. Furthermore, through case studies, we illustrate how behavioral management facilitates timely medical care and monitoring, effectively mitigating stressors that could otherwise impair health and welfare, enabling the provision of care that would have otherwise been unachievable. A thoughtfully designed primate behavioral management program, integrating cooperation and participation with veterinary care, forms the cornerstone of superior animal welfare, enhanced clinical care, and more accurate scientific outcomes.

Longitudinal Baboon (Papio anubis) Neutrophil to Lymphocyte Ratio (NLR), and Correlations with Monthly Sedation Rate and Within-Group Sedation Order.

Neutrophil to lymphocyte ratio (NLR) is a simple marker of stress and inflammation, but there is limited research regarding NLR in nonhuman primates (NHPs), with studies showing associations with longevity, certain medical conditions, and stressful circumstances. Here, we examined baboon NLR longitudinally, and as a function of health parameters. We also examined whether NLR was affected by sedation rate, as well as the order of sedation within a group, given that sedation events during clinical and research practices can induce stress in NHPs. While older adult and geriatric baboon NLR did not differ longitudinally, juvenile and young adult NLR tended to increase, primarily driven by increases in females. Additionally, baboons sedated later within a group showed significantly higher NLRs than those sedated earlier in the process. However, baboons with higher sedation rates per month showed lower NLRs. These data indicate that NLR may be dysregulated in different ways as a function of different types of stress, with sedation order (i.e., acute stress) causing pathological increases in NLR, and sedation rate over time (i.e., chronic stress) causing decreases. Importantly, we propose that NLR, a routinely obtained veterinary measure, has potential utility as a welfare indicator of stress resulting from clinical and research practices, as well as a measure that can inform behavioral management practices and interventions.

Marmoset and human trophoblast stem cells differ in signaling requirements and recapitulate divergent modes of trophoblast invasion.

Early human trophoblast development has remained elusive due to the inaccessibility of the early conceptus. Non-human primate models recapitulate many features of human development and allow access to early postimplantation stages. Here, we tracked the pre- to postimplantation transition of the trophoblast lineage in superficially implanting marmoset embryos in vivo. We differentiated marmoset naive pluripotent stem cells into trophoblast stem cells (TSCs), which exhibited trophoblast-specific transcriptome, methylome, differentiation potential, and long-term self-renewal. Notably, human TSC culture conditions failed to support marmoset TSC derivation, instead inducing an extraembryonic mesoderm-like fate in marmoset cells. We show that combined MEK, TGF-ß/NODAL, and histone deacetylase inhibition stabilizes a periimplantation trophoblast-like identity in marmoset TSCs. By contrast, these conditions differentiated human TSCs toward extravillous trophoblasts. Our work presents a paradigm to harness the evolutionary divergence in implantation strategies to elucidate human trophoblast development and invasion.

Easy to gain but hard to lose: the evolution of the knee sesamoid bones in Primates-a systematic review and phylogenetic meta-analysis.

Sesamoids are variably present skeletal elements found in tendons and ligaments near joints. Variability in sesamoid size, location and presence/absence is hypothesized to enable skeletal innovation, yet sesamoids are often ignored. Three knee sesamoids-the cyamella, medial fabella and lateral fabella-are present in primates, but we know little about how they evolved, if they are skeletal innovations, or why they are largely missing from Hominoidea. Our phylogenetic comparative analyses suggest that sesamoid presence/absence is highly phylogenetically structured and contains phylogenetic signal. Models suggest that it is easy to gain but difficult/impossible to lose knee sesamoids and that the fabellae may have similar developmental/evolutionary pathways that are distinct from the cyamella. Sesamoid presence/absence is uncorrelated to the mode of locomotion, suggesting that sesamoid biomechanical function may require information beyond sesamoid presence, such as size and location. Ancestral state reconstructions were largely uninformative but highlighted how reconstructions using parsimony can differ from those that are phylogenetically informed. Interestingly, there may be two ways to evolve fabellae, with humans evolving fabellae differently from most other primates. We hypothesize that the 're-emergence' of the lateral fabella in humans may be correlated with the evolution of a unique developmental pathway, potentially correlated with the evolution of straight-legged, bipedal locomotion.

Metformin decelerates aging clock in male monkeys.

In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin's influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin's effects on aging. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. Our research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.

Areal specializations in the morpho-electric and transcriptomic properties of primate layer 5 extratelencephalic projection neurons.

Large-scale analysis of single-cell gene expression has revealed transcriptomically defined cell subclasses present throughout the primate neocortex with gene expression profiles that differ depending upon neocortical region. Here, we test whether the interareal differences in gene expression translate to regional specializations in the physiology and morphology of infragranular glutamatergic neurons by performing Patch-seq experiments in brain slices from the temporal cortex (TCx) and motor cortex (MCx) of the macaque. We confirm that transcriptomically defined extratelencephalically projecting neurons of layer 5 (L5 ET neurons) include retrogradely labeled corticospinal neurons in the MCx and find multiple physiological properties and ion channel genes that distinguish L5 ET from non-ET neurons in both areas. Additionally, while infragranular ET and non-ET neurons retain distinct neuronal properties across multiple regions, there are regional morpho-electric and gene expression specializations in the L5 ET subclass, providing mechanistic insights into the specialized functional architecture of the primate neocortex.

Chronic Kidney Disease and Kidney Stone in a Wild Chimpanzee (Pan troglodytes verus) in Côte d'Ivoire.

An older wild female chimpanzee (Pan troglodytes) was found dead with a large calcium oxalate stone in the renal pelvis. Histopathological changes included glomerulosclerosis, interstitial nephritis and fibrosis, focal mineralization, and medial hypertrophy. Urinary albumin-creatinine-ratio showed increased values from 15 months before death. Causes of the kidney disease remain unconfirmed.

Variation in Craniodental Pathologies Among Cercopithecoid Primates.

Pathologies of the skull and teeth are well documented for many human populations, but there are fewer studies of other primates. We contrast lesion prevalence and patterning among cercopithecoid primates and map variation onto socioecological variables. We compare craniodental lesions in six species: Nasalis larvatus (n = 54), Colobus polykomos (n = 64), Cercopithecus mitis (n = 65), Macaca fascicularis (n = 109), Theropithecus gelada (n = 13), and Papio anubis (n = 76). One of us (C.A.K.) evaluated each adult skull for multiple lesion types using standard criteria. We also tested for a relationship between lesion prevalence and cranial suture fusion (age proxy). We used nonparametric tests for sex and species differences as well as pathology co-occurrence in SPSS. Socioecological data come from previous studies. Sex differences in lesion prevalence were only detected in P. anubis. Within taxa, some lesion types co-occurred. In Macaca, the presence of caries was associated with several other lesion types. Pulp cavity exposure co-occurred with TMJ osteoarthritis in multiple taxa. Among taxa, male P. anubis had higher lesion prevalences, particularly related to the anterior dentition and facial trauma. Because we did not detect a relationship between suture fusion and lesion prevalence, we propose that craniodental lesions may also be influenced by socioecological variables such as group composition and ratio of fruit to leaves in the diet. Our findings suggest that pain from pulp cavity exposure and related dental infections may alter chewing biomechanics and contribute to onset of TMJ osteoarthritis in nonhuman primates, as seen in humans. Further, we suggest that higher lesion prevalence in male baboons is likely related to male-male competition. Skeletal lesion analysis provides useful insight into primate socioecology, particularly for rare or difficult-to-observe phenomena, and provides additional biological context for our own species.

Comparative single-cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea.

Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age-related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single-cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue-specific aging and developing new therapies targeting ROS damage.