Development of a cyclophosphamide stress test to predict resilience to aging in mice

Zhu, Lida; Dou, Yan; Bjorner, Marianne; Ladiges, Warren

doi:10.1007/s11357-020-00222-z

Cited by 3 publications

(3 citation statements)

References 25 publications

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“…Neutrophil rebound negatively correlated with escape speed from a box maze, a learning paradigm where higher speeds are associated with resilience to agerelated cognitive decline (Figure 4B). In summary, one non-lethal dose of CYP induced a neutrophil rebound response that was consistent over all age groups as previously reported [4]. The rebound strength decreased with increasing age, so it was age-dependent.…”

supporting

confidence: 88%

Neutrophil response to cyclophosphamide predicts resilience to age-related learning impairment

Nickel

Bjorner

Ladiges

et al. 2020

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The ability to respond to stress, defined as resilience, was measured by white blood cell counts in C57BL/6 mice of various ages receiving a nonlethal dose of cyclophosphamide (CYP). Neutrophil counts dipped and then rebounded in a consistent and age-dependent manner. Low neutrophil rebound correlated with improved learning in middle-age mice suggesting CYP-nduced neutrophil response may predict resilience to aging. Keywords: Resilience to aging, wound healing, ear punch biopsy, aging mice

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supporting

confidence: 88%

Neutrophil response to cyclophosphamide predicts resilience to age-related learning impairment

Nickel

Bjorner

Ladiges

et al. 2020

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“…Indeed, resilience is a dynamic process, and the speed of recovery can be determined and quantified depending on the stressor. For example, the response to and recovery from a nonlethal dose of the chemotherapeutic drug cyclophosphamide, which targets myeloid precursor cells, can easily be determined by a simple white blood cell count measuring the acute decrease with challenge and gradual recovery of cells [12].…”

Section: Organismal Resiliencementioning

confidence: 99%

Resilience to aging is a heterogeneous characteristic defined by physical stressors

Lei¹,

Huffman²,

Salmon³

et al. 2022

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Physical resilience, the capacity to respond to and recover from a stressful event, declines with advancing age. Individuals respond differently to physical stressors across their lifespans. While the biological underpinnings of resilience remain unclear, a plausible determinant is the capacity of an individual’s cellular and molecular levels to return to homeostasis after a physical challenge. Impaired resilience may not only be a consequence of aging but could also be a contributing factor to the aging process. Therefore, resilience at relatively younger ages could be predictive of future health and lifespan. By utilizing standardized physical challenges and measuring stress response patterns, the relative resilience of individuals can be quantified and classified. Current preclinical research suggests that several physical stressors could be used to measure resilience in clinical aging studies. A mechanistic understanding of why some individuals are more resilient to physical stressors than others could help identify protective factors and therapeutic ways to promote healthy aging. Keywords: Physical resilience to aging, physical stressors, heterogeneity, stress response patterns, healthy aging, therapeutic resilience

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“…One area of current biological research on resilience and aging is focused on developing physical stress tests that actually predict resilience to aging in animal models. For example, in older naïve mice, a non-lethal dose of the drug cyclophosphamide triggers a response in the white blood cell population such that the neutrophil lymphocyte ratio predicts more youthful cognition and physical activity in a subset of mice with increasing age [2]. Another example is immune response to a vaccine.…”

mentioning

confidence: 99%

Precision aging. Human lifespan has intrinsic limits but measurable outcomes

Ladiges

2021

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Development of a cyclophosphamide stress test to predict resilience to aging in mice

Cited by 3 publications

References 25 publications

Neutrophil response to cyclophosphamide predicts resilience to age-related learning impairment

Neutrophil response to cyclophosphamide predicts resilience to age-related learning impairment

Resilience to aging is a heterogeneous characteristic defined by physical stressors

Precision aging. Human lifespan has intrinsic limits but measurable outcomes

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