Age-Associated Pathology in Rhesus Macaques (<i>Macaca mulatta</i>)

Simmons, Heather A.

doi:10.1177/0300985815620628

Cited by 93 publications

(88 citation statements)

References 77 publications

(180 reference statements)

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“…Ten animals were assessed per age group separately by two veterinary pathologists. Organ composite scores were created using published aged lesions from each organ as a general guideline [17]. Lesions assessed in the renal composite score included glomerular changes (membranous thickening of Bowman's capsule, synechiation, and glomerulosclerosis), degree of medullary interstitial accumulations (fibrosis and/or amyloid), degree of infarction, and presence of vascular changes.…”

Section: Geropathology In Rhesus Macaquesmentioning

confidence: 99%

Development of a Geropathology Grading Platform for nonhuman primates

Olstad

Imai

Keesler

et al. 2020

APT

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A geropathology grading platform (GGP) for assessing age-related lesions has been established and validated for in inbred strain of mice. Because nonhuman primates (NHPs) share significant similarities in aging and spontaneous chronic diseases with humans, they provide excellent translational value for correlating histopathology with biological and pathological events associated with increasing age. Descriptive age-associated pathology has been described for rhesus macaques and marmosets, but a grading platform similar to the mouse GGP does not exist. The value of these NHP models is enhanced by considerable historical data from clinical, bio-behavioral, and social domains that align with health span in these animals. Successful adaptation of the mouse GGP for NHPs will include 1) expanding the range of organs examined; 2) standardizing necropsy collection, tissue trimming, and descriptive lesion terminology; 3) expanding beyond rhesus macaques and marmosets to include other commonly used NHPs in research; and 4) creating a national resource for age-related pathology to complement the extensive in-life datasets. Adaptation of the GGP to include translational models other than mice will be crucial to advance geropathology designed to enhance aging research.

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Section: Geropathology In Rhesus Macaquesmentioning

confidence: 99%

Development of a Geropathology Grading Platform for nonhuman primates

Olstad

Imai

Keesler

et al. 2020

APT

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“…Table 1 Example of diseases and traits reported in rhesus macaques. Diseases are grouped based on whether a genetic association has been reported in macaques for that disease Genetic Association Reported SIV progression [1][2][3] Age-related macular degeneration [4,5] Colorectal cancer [6] Krabbe disease [7] Ammenorhea [8] Naltrexone response [9] HPA axis dysregulation [10] Alcohol intake levels [11][12][13] Anxiety [14,15] No Genetic Association Reported Autism [16] Age-associated coginitive decline [17] Polycystic ovary syndrome (PCOS) [18] Endometriosis [19][20][21] Left ventricular hypertrophy [22] Type III Von-Willebrand [23] Type II Diabetes [24][25][26] Squamous cell carcinoma [27] Coat-like retinopathy [28] TB progression [29] Osteoporosis [30]…”

Section: Introductionmentioning

confidence: 99%

mGAP: the macaque genotype and phenotype resource, a framework for accessing and interpreting macaque variant data, and identifying new models of human disease

et al. 2019

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Background Non-human primates (NHPs), particularly macaques, serve as critical and highly relevant pre-clinical models of human disease. The similarity in human and macaque natural disease susceptibility, along with parallel genetic risk alleles, underscores the value of macaques in the development of effective treatment strategies. Nonetheless, there are limited genomic resources available to support the exploration and discovery of macaque models of inherited disease. Notably, there are few public databases tailored to searching NHP sequence variants, and no other database making use of centralized variant calling, or providing genotype-level data and predicted pathogenic effects for each variant. Results The macaque Genotype And Phenotype (mGAP) resource is the first public website providing searchable, annotated macaque variant data. The mGAP resource includes a catalog of high confidence variants, derived from whole genome sequence (WGS). The current mGAP release at time of publication (1.7) contains 17,087,212 variants based on the sequence analysis of 293 rhesus macaques. A custom pipeline was developed to enable annotation of the macaque variants, leveraging human data sources that include regulatory elements (ENCODE, RegulomeDB), known disease- or phenotype-associated variants (GRASP), predicted impact (SIFT, PolyPhen2), and sequence conservation (Phylop, PhastCons). Currently mGAP includes 2767 variants that are identical to alleles listed in the human ClinVar database, of which 276 variants, spanning 258 genes, are identified as pathogenic. An additional 12,472 variants are predicted as high impact (SnpEff) and 13,129 are predicted as damaging (PolyPhen2). In total, these variants are predicted to be associated with more than 2000 human disease or phenotype entries reported in OMIM (Online Mendelian Inheritance in Man). Importantly, mGAP also provides genotype-level data for all subjects, allowing identification of specific individuals harboring alleles of interest. Conclusions The mGAP resource provides variant and genotype data from hundreds of rhesus macaques, processed in a consistent manner across all subjects ( https://mgap.ohsu.edu ). Together with the extensive variant annotations, mGAP presents unprecedented opportunity to investigate potential genetic associations with currently characterized disease models, and to uncover new macaque models based on parallels with human risk alleles. Electronic supplementary material The online version of this article (10.1186/s12864-019-5559-7) contains supplementary material, which is available to authorized users.

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“…Rhesus macaques are also one of the most commonly used animal models in basic and applied biomedical research on human disease [1,2]. Previous research has also established that rhesus macaques and humans share approximately 95% genetic homology and have very similar age-associated conditions including diabetes, osteoarthritis, endometriosis, visual accommodation, hypertension, osteoporosis, and amyloidosis [2].…”

Section: Introductionmentioning

confidence: 99%

“…The brain architecture of the rhesus macaque is also very similar to that in humans and displays comparable age-related cognitive decline [2][3][4]. Investigating the molecular mechanism of the normal aging of rhesus brain has received considerable critical attention.…”

Section: Introductionmentioning

confidence: 99%

Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys

Meng

Xia

Pan

et al. 2019

Preprint

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Background: Aged rhesus monkeys exhibit deficits in memory mediated by the hippocampus. Although extensive research has been carried out on the characteristics of human hippocampal aging, there is still very little scientific understanding of the changes associated with hippocampal aging in rhesus monkeys. To explore the proteomics profiling and pathway-related changes in the rhesus hippocampus during the aging process, we conducted a high throughput quantitative proteomics analysis of hippocampal samples from two groups of rhesus macaques aged 6 years and 20 years, using 2-plex tandem mass tag (TMT) labeling. In addition, we used a comprehensive bioinformatics analysis approach to investigate the enriched signaling pathways of differentially expressed proteins (the ratios of 20-y vs. 6-y, ≥1.20 or ≤ 0.83). Results: In total, 3,260 proteins were identified with a high level of confidence in rhesus hippocampus. We found 367 differentially expressed proteins related to rhesus hippocampus aging. Based on biological pathway analysis, we found these aging-related proteins were predominantly enriched in the electron transport chain, NRF2 pathway, focal adhesion-PI3K-AKT-mTOR signaling pathway and cytoplasmic ribosome proteins. Data are available via ProteomeXchange with identifier PXD011398. Conclusion: This study provides a detail description of the proteomics profile related to rhesus hippocampal aging. These findings should make an important contribution to further mechanistic studies, marker selection and drug development for the prevention and treatment of aging or age-related neurodegeneration.

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Age-Associated Pathology in Rhesus Macaques (Macaca mulatta)

Cited by 93 publications

References 77 publications

Development of a Geropathology Grading Platform for nonhuman primates

Development of a Geropathology Grading Platform for nonhuman primates

mGAP: the macaque genotype and phenotype resource, a framework for accessing and interpreting macaque variant data, and identifying new models of human disease

Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys

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