Abstract
In vivo micro-CT has already been used to monitor microstructural changes of bone in mice of different ages and in models of age-related diseases such as osteoporosis. However, as aging is accompanied by frailty and subsequent increased sensitivity to external stimuli such as handling and anesthesia, the extent to which longitudinal imaging can be applied in aging studies remains unclear. Consequently, the potential of monitoring individual mice during the entire aging process–from healthy to frail status–has not yet been exploited. In this study, we assessed the effects of long-term in vivo micro-CT imaging—consisting of 11 imaging sessions over 20 weeks—on hallmarks of aging both on a local (i.e., static and dynamic bone morphometry) and systemic (i.e., frailty index (FI) and body weight) level at various stages of the aging process. Furthermore, using a premature aging model (PolgA(D257A/D257A)), we assessed whether these effects differ between genotypes. The 6th caudal vertebrae of 4 groups of mice (PolgA(D257A/D257A) and PolgA(+/+)) were monitored by in vivo micro-CT every 2 weeks. One group was subjected to 11 scans between weeks 20 and 40 of age, whereas the other groups were subjected to 5 scans between weeks 26–34, 32–40 and 40–46, respectively. The long-term monitoring approach showed small but significant changes in the static bone morphometric parameters compared to the other groups. However, no interaction effect between groups and genotype was found, suggesting that PolgA mutation does not render bone more or less susceptible to long-term micro-CT imaging. The differences between groups observed in the static morphometric parameters were less pronounced in the dynamic morphometric parameters. Moreover, the body weight and FI were not affected by more frequent imaging sessions. Finally, we observed that longitudinal designs including baseline measurements at young adult age are more powerful at detecting effects of in vivo micro-CT imaging on hallmarks of aging than cross-sectional comparisons between multiple groups of aged mice subjected to fewer imaging sessions.
Highlights
With the estimated increase in life expectancy in the 30 years [1], the number of people suffering from frailty will substantially increase [2, 3]
While BV/TV, Tb.Th, Ct.Ar/Tt.Ar and Ct.Th initially increased in both genotypes, the increase in these parameters ceased to continue in PolgA mice from 30–32 weeks onwards (Fig 2A–2D)
Inspired by a previous study, which characterized the bone phenotype and the development of frailty in the PolgA mouse model [41], this study assessed the impact of long-term in vivo micro-CT imaging on hallmarks of osteopenia and frailty in individual mice during the process of aging
Summary
With the estimated increase in life expectancy in the 30 years [1], the number of people suffering from frailty will substantially increase [2, 3]. We compared static and dynamic bone morphometric parameters as well as body weight and FI measurements of PolgA(+/+) (in the following referred to as WT) and PolgA(D257A/D257A) (in the following referred to as PolgA) mice subjected to 11 consecutive imaging sessions with those of mice subjected to 5 consecutive imaging sessions at various ages By performing both cross-sectional comparisons between genotypes and between imaging groups (i.e., that were scanned at different time-points) as well as longitudinal comparisons within individual animals (i.e., that were scanned both at young adult and old age), we aimed to provide important insight for the effective design of studies applying in vivo micro-CT imaging in aging mice
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