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Resilience, aging, and response to radiation exposure (RARRE) in nonhuman primates: a resource review

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GEROSCIENCE
卷 -, 期 -, 页码 -

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SPRINGER
DOI: 10.1007/s11357-023-00812-7

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Resilience; Biology of aging; Multimorbidity; Nonhuman primates; Animal models; Ionizing radiation

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The Wake Forest nonhuman primate (NHP) Radiation Late Effects Cohort (RLEC) is a vital population that helps us understand the late effects of radiation exposure. This cohort has evaluated over 250 previously irradiated rhesus macaques, providing valuable insights on resilience and biological aging. By considering individual differences in response to radiation, we can develop strategies to manage late radiation effects and understand mechanisms underlying resilience and aging.
The Wake Forest nonhuman primate (NHP) Radiation Late Effects Cohort (RLEC) is a unique and irreplaceable population of aging NHP radiation survivors which serves the nation's need to understand the late effects of radiation exposure. Over the past 16 years, Wake Forest has evaluated > 250 previously irradiated rhesus macaques (Macaca mulatta) that were exposed to single total body irradiation (IR) doses of 1.14-8.5 Gy or to partial body exposures of up to 10 Gy (5% bone marrow sparing) or 10.75 Gy (whole thorax). Though primarily used to examine IR effects on disease-specific processes or to develop radiation countermeasures, this resource provides insights on resilience across physiologic systems and its relationship with biological aging. Exposure to IR has well documented deleterious effects on health, but the late effects of IR are highly variable. Some animals exhibit multimorbidity and accumulated health deficits, whereas others remain relatively resilient years after exposure to total body IR. This provides an opportunity to evaluate biological aging at the nexus of resilient/vulnerable responses to a stressor. Consideration of inter-individual differences in response to this stressor can inform individualized strategies to manage late effects of radiation exposure, and provide insight into mechanisms underlying systemic resilience and aging. The utility of this cohort for age-related research questions was summarized at the 2022 Trans-NIH Geroscience Interest Group's Workshop on Animal Models for Geroscience. We present a brief review of radiation injury and its relationship to aging and resilience in NHPs with a focus on the RLEC.

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