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Nutrition, metabolism, and targeting aging in nonhuman primates.

ABSTRACT: This short review focuses on the importance of nonhuman primate nutrition and aging studies and makes the case that a targeted expansion of the use of this highly translatable model would be advantageous to the biology of aging field. First, we describe the high degree of similarity of the model in terms of aging phenotypes including incidence and prevalence of common human age-related diseases. Second, we discuss the importance of the nonhuman primate nutrition and aging studies and the extent to which the outcomes of two ongoing long-term studies of caloric restriction are congruent with short-term equivalent studies in humans. Third, we showcase a number of pharmacological agents previously employed in nonhuman primate studies that display some potential as caloric restriction mimetics. Finally, we present nonhuman primates as an important model for translation of mechanisms of delayed aging identified in studies of shorter-lived animals. Proof of efficacy and safety of candidate longevity agents in nonhuman primates would be a cost-effective means to bring these exciting new avenues a step closer to clinical application.

SUBMITTER: Balasubramanian P

PROVIDER: S-EPMC5563491 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Nutrition, metabolism, and targeting aging in nonhuman primates.

Balasubramanian Priya P Mattison Julie A JA Anderson Rozalyn M RM

Ageing research reviews 20170220

This short review focuses on the importance of nonhuman primate nutrition and aging studies and makes the case that a targeted expansion of the use of this highly translatable model would be advantageous to the biology of aging field. First, we describe the high degree of similarity of the model in terms of aging phenotypes including incidence and prevalence of common human age-related diseases. Second, we discuss the importance of the nonhuman primate nutrition and aging studies and the extent ...[more]

PMID: 28219777

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Project description:We recently developed the radiotracer 4-[(3-iodophenyl)amino]-7-(2-[2-{2-(2-[2-{2-((18)F-fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide) ((18)F-PEG(6)-IPQA) for noninvasive detection of active mutant epidermal growth factor receptor kinase-expressing non-small cell lung cancer xenografts in rodents. In this study, we determined the pharmacokinetics, biodistribution, metabolism, and radiation dosimetry of (18)F-PEG(6)-IPQA in nonhuman primates.Six rhesus macaques were injected intravenously with 141 ± 59.2 MBq of (18)F-PEG(6)-IPQA, and dynamic PET/CT images covering the thoracoabdominal area were acquired for 30 min, followed by whole-body static images at 60, 90, 120, and 180 min. Blood samples were obtained from each animal at several time points after radiotracer administration. Radiolabeled metabolites in blood and urine were analyzed using high-performance liquid chromatography. The (18)F-PEG(6)-IPQA pharmacokinetic and radiation dosimetry estimates were determined using volume-of-interest analysis of PET/CT image datasets and blood and urine time-activity data.(18)F-PEG(6)-IPQA exhibited rapid redistribution and was excreted via the hepatobiliary and urinary systems. (18)F-PEG(6) was the major radioactive metabolite. The critical organ was the gallbladder, with an average radiation-absorbed dose of 0.394 mSv/MBq. The other key organs with high radiation doses were the kidneys (0.0830 mSv/MBq), upper large intestine wall (0.0267 mSv/MBq), small intestine (0.0816 mSv/MBq), and liver (0.0429 mSv/MBq). Lung tissue exhibited low uptake of (18)F-PEG(6)-IPQA due to the low affinity of this radiotracer to wild-type epidermal growth factor receptor kinase. The effective dose was 0.0165 mSv/MBq. No evidence of acute cardiotoxicity or of acute or delayed systemic toxicity was observed. On the basis of our estimates, diagnostic dosages of (18)F-PEG(6)-IPQA up to 128 MBq (3.47 mCi) per injection should be safe for administration in the initial cohort of human patients in phase I clinical PET studies.The whole-body and individual organ radiation dosimetry characteristics and pharmacologic safety of diagnostic dosages of (18)F-PEG(6)-IPQA in nonhuman primates indicate that this radiotracer should be acceptable for PET/CT studies in human patients.

Dataset Information

Nutrition, metabolism, and targeting aging in nonhuman primates.

Publications

Nutrition, metabolism, and targeting aging in nonhuman primates.

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