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 NHPs that survived to adulthood and died of natural/health-related causes.

Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons. While there has been significant progress in defining the genetic contributions to ALS, greater than 90 ​% of cases are sporadic, which suggests an environmental component. The gut microbiota is altered in ALS and is an ecological factor that contributes to disease by modulating immunologic, metabolic, and neuronal signaling.

Maternal under-nutrition during pregnancy alters the molecular response to over-nutrition in multiple organs and tissues in nonhuman primate juvenile offspring.

Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON).

[F]F-AraG Uptake in Vertebral Bone Marrow May Predict Survival in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-(L)1 Immunotherapy.

Despite the systemic impact of both cancer and the associated immune response, immuno-PET is predominantly centered on assessment of the immune milieu within the tumor microenvironment. The aim of this study was to assess the value of [F]F-AraG PET imaging as a noninvasive method for evaluation of system-wide immune status of patients with non-small cell lung cancer before starting immunotherapy. Eleven patients with advanced non-small cell lung cancer were imaged with [F]F-AraG before starting immunotherapy.

Cognitive Effects of Simulated Galactic Cosmic Radiation Are Mediated by ApoE Status, Sex, and Environment in APP Knock-In Mice.

Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer's disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.

Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation via Hexosamine Biosynthetic Pathway.

Age is a prominent risk factor for cardiometabolic disease, often leading to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction exclusively resulting from physiological aging remain elusive. Previous research demonstrated age-related functional alterations in baboons, analogous to humans.

Meta-analysis identifies common gut microbiota associated with multiple sclerosis.

Background: Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies.

Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis.

Dietary proteins are taken up by intestinal dendritic cells (DCs), cleaved into peptides, loaded to major histocompatibility complexes, and presented to T cells to generate an immune response. Amino acid (AA)-diets do not have the same effects because AAs cannot bind to major histocompatibility complex to activate T cells. Here, we show that impairment in regulatory T cell generation and loss of tolerance in mice fed a diet lacking whole protein is associated with major transcriptional changes in intestinal DCs including downregulation of genes related to DC maturation, activation and decreased gene expression of immune checkpoint molecules.

Perinatal maternal undernutrition in baboons modulates hepatic mitochondrial function but not metabolites in aging offspring.

We previously demonstrated in baboons that maternal undernutrition (MUN), achieved by 70 % of control nutrition, impairs fetal liver function, but long-term changes associated with aging in this model remain unexplored. Here, we assessed clinical phenotypes of liver function, mitochondrial bioenergetics, and protein abundance in adult male and female baboons exposed to MUN during pregnancy and lactation and their control counterparts. Plasma liver enzymes were assessed enzymatically.

Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer's disease mouse models.

The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aβ plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression.

Genetic characterization of a captive marmoset (Callithrix jacchus) colony using genotype-by-sequencing.

The marmoset is a fundamental nonhuman primate model for the study of aging, neurobiology, and many other topics. Genetic management of captive marmoset colonies is complicated by frequent chimerism in the blood and other tissues, a lack of tools to enable cost-effective, genome-wide interrogation of variation, and historic mergers and migrations of animals between colonies. We implemented genotype-by-sequencing (GBS) of hair follicle derived DNA (a minimally chimeric DNA source) of 82 marmosets housed at the Southwest National Primate Research Center (SNPRC).

Differential mitochondrial bioenergetics and cellular resilience in astrocytes, hepatocytes, and fibroblasts from aging baboons.

Biological resilience, broadly defined as the ability to recover from an acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences are likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue, and subject level.

Genetic regulatory effects in response to a high-cholesterol, high-fat diet in baboons.

Steady-state expression quantitative trait loci (eQTLs) explain only a fraction of disease-associated loci identified through genome-wide association studies (GWASs), while eQTLs involved in gene-by-environment (GxE) interactions have rarely been characterized in humans due to experimental challenges. Using a baboon model, we found hundreds of eQTLs that emerge in adipose, liver, and muscle after prolonged exposure to high dietary fat and cholesterol. Diet-responsive eQTLs exhibit genomic localization and genic features that are distinct from steady-state eQTLs.

Differential mitochondrial bioenergetics and cellular resilience in astrocytes, hepatocytes, and fibroblasts from aging baboons.

Biological resilience, broadly defined as ability to recover from acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue and subject level.

Female baboon adrenal zona fasciculata and zona reticularis regulatory and functional proteins decrease across the life course.

Debate exists on life-course adrenocortical zonal function trajectories. Rapid, phasic blood steroid concentration changes, such as circadian rhythms and acute stress responses, complicate quantification. To avoid pitfalls and account for life-stage changes in adrenocortical activity indices, we quantified zonae fasciculata (ZF) and reticularis (ZR) across the life-course, by immunohistochemistry of key regulatory and functional proteins.

Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation Via Hexosamine Biosynthetic Pathway.

Age is a prominent risk factor for cardiometabolic disease, and often leads to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction resulting from physiological aging per se remain elusive. Understanding these mechanisms requires biological models with optimal translation to humans.

The Use of HIV Pre-exposure Prophylaxis Among Men Accessing Routine Sexual and Reproductive Health Services in South Africa.

Purpose: This study describes a cohort of men seeking oral pre-exposure prophylaxis (PrEP) services and explores their patterns of PrEP use within an implementation project seeking to integrate PrEP provision within sexual and reproductive health services in public health clinics in South Africa.

Methods: Routine program and survey data from 364 males initiated on oral PrEP between July 2020 and May 2022 were analyzed. PrEP use was examined, including time to first discontinuation and restart patterns.

Patterns of HIV Pre-exposure Prophylaxis use Among Adolescent Girls and Young Women Accessing Routine Sexual and Reproductive Health services in South Africa.

Purpose: This study describes the patterns of pre-exposure prophylaxis (PrEP) use among adolescent girls and young women (AGYW) initiated on daily oral PrEP for the prevention of HIV, within routine sexual and reproductive health services in South Africa.

Methods: We analysed clinical and survey data from a nested cohort of 967 AGYW initiated on oral PrEP between January 2019 and December 2021 in four geographical clusters in South Africa. We describe the periods of PrEP use, and the proportion who discontinued and subsequently restarted PrEP.

Mental Health Needs of Adolescent and Young Adult PrEP Users in South Africa: Implications for Sexual and Reproductive Health Programming.

Purpose: Poor mental health is associated with sexual and reproductive health (SRH) risks, including human immunodeficiency virus (HIV) and pre-exposure prophylaxis discontinuation. Adolescents and young people (AYP) are vulnerable to HIV and depression. This paper describes the prevalence and severity of depression and associated factors in AYP accessing SRH services in South Africa.

Comparing the Integration of Syndromic versus Etiological Management of Sexually Transmitted Infections Into HIV Pre-Exposure Prophylaxis Services for Adolescent Girls and Young Women, in South Africa.

Unlabelled: South Africa has a high incidence of human immunodeficiency virus and sexually transmitted infections (STIs), particularly among adolescent girls and young women. National and global guidelines recommend varied strategies for integrating STI and pre-exposure prophylaxis (PrEP) services.

Purpose: This paper describes the implementation of a syndromic compared to an etiological approach to STI integration within PrEP services in South Africa.