Cross-sectional comparison of health-span phenotypes in young versus geriatric marmosets

Abstract

The development of the marmoset as a translational model for healthspan and lifespan studies relies on the characterization of health parameters in young and geriatric marmosets. This cross-sectional study examined health phenotypes in marmosets for five domains of interest for human health and aging: mobility, cognition, metabolism, homeostasis, and immune function. Geriatric marmosets were found to have significant executive function impairment when compared to young animals. While geriatric animals did not show gross abnormalities in mobility and measures of locomotion, their types of movement were altered from young animals. Geriatric marmosets had alterations in cardiac function, with significantly increased mean arterial pressures; metabolism, with significantly lower VO₂ ; and suppressed immune function. Further, this study sought to characterize and describe histopathology for both young and geriatric healthy marmosets. Overall this study provides a characterization of health parameters for young and geriatric marmosets which will greatly enhance future aging and interventional testing in marmosets.

Keywords: animal models; biomarkers of aging; healthspan; longevity; nonhuman primates.

Figure 1-

Marmoset activity behaviors recorded during ten-minute behavioral observations. The average number per minute (± SE) of transitions between quadrants of the cage, leaping, grooming, hanging (stretch), scent mark and genital displays. Geriatric marmosets made significantly fewer transitions between quadrants of the cage than did young animals (F(1, 37)=14.126, p = 0.001), as well as performing fewer leaps (F(1,37) = 24.48, p = 0.0001).

Figure 2 –

Daily activity counts as recorded by an actimeter worn by the animals for 48 hours, there were no significant differences between geriatric and young animals (t = 1.774, p=0.10).

Figure 3 –

Cognitive function assessed via the detoured reach cognitive function task. The average number of successful trials (± SE) during each session for geriatric and young animals. Session 6 was the first test session following the two reengagement sessions and the altering of the presentation order for the test trials. Young animals were significantly more successful at the task (F(7,91)=2.495, p=0.022).

Figure 4 –

Average VO₂ (ml O₂/hour) for young and geriatric marmosets as measured by indirect calorimetry. Geriatric animals had significantly reduced VO₂ (F(1,15) = 4.844, p = 0.044).

Figure 5 –

Mean arterial pressure was significantly higher for geriatric marmosets than for young marmosets (t= 3.562, df = 34, p = 0.0011).

Figure 6 –

Young animals displayed a wide range of times for arousal in the morning as compared to the later time and narrower time range of arousal for the geriatric animals (t=3.333, df = 11, p=0.0067).

Figure 7 -

Analysis of cellular function by flow cytometry revealed that older animals had significantly lower expression of proliferation markers as measured by CD25 in B cells (F(1,16)=18.19, p=0.001), and T4 cells (F(1,16)=7.58, p=0.014). Older animals also expressed heightened pro-inflammatory states as displayed by increased activation of HLA-DR in CD8 cells (F(1,16)=10.29, p=0.005) and CD4 cells (F(1,16)=25.27, p=0.000). Older animals also had a lower percentage of B cells (F(1,16)=4.51, p=0.05) and higher percentage of T-cells F(1,16)=13.8, p=0.002).